2,4-pyrimidindiamine compounds having effect in case of autoimmune disorders

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to novel 2,4-pyridindiamine compounds of formula (1). In structural formula (I) L1 is direct bond; L2 is direct bond; R2 is phenyl group, three times substituted with three groups R8; R4 is X represents N; Y is selected from group consisting of O, NH, S, SO and SO2; Z is selected from group consisting of O, NH; on condition that if Y is selected from group consisting of NH, S, SO and SO2, Z is not the same as Y; R5 is selected from group consisting from R6, halogen; each R6 is independently selected from group consisting of hydrogen, halogen; R8 is selected from group consisting from Ra, Rb, Ra substituted with one or several similar or different groups Ra or Rb, -ORa, -O-CHRaRb; each R35 independently on others is selected from group consisting of hydrogen and R35, or in alternative case, two groups R35, bound to one and the same carbon atom are taken together with formation of oxogroup (=O), and the remaining two groups R35 each independently on each other are selected from group consisting from hydrogen and R8; each Ra is independently selected from group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl; each Rb is suitable group which is independently selected from group consisting of -ORd, halogen, -CF3, -C(O)NRcRc, and -OC(O)ORd; each Rc is independently protective group or Ra; each Rd is independently protective group or Ra; each index m is independently integer number from 1 to 3.

EFFECT: novel compounds can be used for treatment or prevention of autoimmune diseases, for instance such as rheumatoid arthritis and/or related to it symptoms, systemic lupus erythematosus and/or related to it symptoms, as well as and/or related to it symptoms.

41 cl, 14 dwg, 1 ex

 

1. CROSS REFERENCES TO RELATED APPLICATIONS

According to § 119(e) of part 35 of the U.S.C. (United States Code U.S.C.) according to the present application claims priority from the following applications: registration number 60/491641, filing date July 30, 2003 (case number a patent attorney 28575/US/US/2); registration number 60/531598, filing date December 19, 2003 (case number a patent attorney 28575/US/8) and registration number 60/572256, filing date may 15, 2004 (case number a patent attorney 28575/US/9).

2. The SCOPE of the INVENTION

The present invention generally relates to compounds 2,4-pyrimidinediamine, pharmaceutical compositions containing these compounds, to intermediate compounds and synthetic methods for producing such compounds and methods of using these compounds and compositions in various areas, for example in the treatment or prevention of autoimmune diseases and / or symptoms associated with these diseases.

3. The BACKGROUND TO the INVENTION

Crosslinking Fc receptors, such as receptor with high affinity for IgE (FcεRI) and/or the receptor with high affinity for IgG (FcγRI), activates a signaling cascade in mastocyte, basophils and other immune cells, resulting in the secretion of chemical mediators responsible for a number of adverse effects. In the example, this binding results in the release of preformed mediators of anaphylactic reactions of type I hypersensitivity (immediate reaction), such as histamine, from areas of accumulation in grains through degranulation. It also leads to synthesis and release of other mediators, including leukotrienes, prostaglandins and factors of activated platelets (PAF), which play an important role in the course of inflammatory reactions. Additional mediators that are synthesized and secreted in the crosslinking Fc receptors include cytokines and nitric oxide.

Signaling cascade or cascade activated in the crosslinking Fc receptors, such as FcεRI and/or FcγRI, consist of a set of cellular proteins. One of the most important distributors of intercellular signals are tyrosine kinase. An important receptor involved in the establishment of signal transduction associated with the binding of the receptor FcεRI and/or FcγRI, as well as other signal transduction cascades, is a Syk-kinase (for review see Valentet al., 2002,Intl. J. Hematol.75(4):257-362).

As mediators, isolated from the fusion receptor FcεRI and FcγRI are responsible or play an important role in the manifestation of numerous adverse events, it is highly desirable to have a compound capable to inhibit ignaliny cascade or cascade, responsible for their selection. Moreover, given the critical role of Syk kinase in the signaling cascade (cascade) of these and other receptors, the presence of compounds able to inhibit Syk-kinase, is also very desirable.

4. BRIEF description of the INVENTION

One aspect of the present invention is to propose novel compounds 2,4-pyrimidinediamine, which, as will be described in detail below, show biological activity in a number of ways. These compounds generally consist of 2,4-pyrimidinediamine "kernel", which has the following structure and numbering system:

These compounds according to the present invention are substituted in the place of attachment of the nitrogen (N2) to the atom C2 with the formation of a secondary amine and may be further substituted in one or more positions: at the connection point of nitrogen (N4) to the atom C4, C5 and/or C6. With the substitution of the node N4 Deputy forms a secondary amine. Deputy node N2, and possible substituents in other positions can vary greatly in nature and physico-chemical properties. For example, the Deputy (deputies) may be a branched, unbranched or cyclic alkyl, a branched, unbranched or cyclic heteroalkyl, mono - or polycyclic heteroaryl or a combination of these groups. This is the group substitution may further be substituted, as described in detail below.

Deputy N2 and/or N4 can join directly to the respective nitrogen atoms or to be separated from the respective nitrogen atoms via linkers, which may be the same or different. The nature of the linkers can vary widely and can include almost any combination of atoms or groups suitable for the separation of one part of the molecule from another. For example, the linker can be a bridge from acyclic hydrocarbon (for example, saturated or unsaturated alkylene-such as methane-, ethane-, Aten-, propane-, 1-propene, butane, 1-butene-2-butene, 1,3-butadiene and the like), the bridge of the monocyclic or polycyclic hydrocarbon (for example, 1,2-benzene, 2,3-naphthalene - and the like), a simple acyclic heteroatomic bridge or heteroalicyclic bridge (for example, -O-, -S-, S-O-, -NH-, -PH-, -C(O)-, -C(O)NH-, -S(O)-, -S(O)2-, -S(O)NH-, -S(O)2NH-, -O-CH2-, -CH2-O-CH2-, -O-CH=CH-CH2- and the like), a monocyclic or polycyclic heteroaryl bridge (for example,, [3,4]-furan, pyridine, thiophene, piperidine, piperazine, pyridin, pyrrolidin - and the like) or a combination of the listed bridges.

The substituents in positions N2, N4, C5 and/or C6, as well as potential linkers may further be substituted by one or more identical or different is a group of substitution. The nature of these substitution groups may vary within wide limits. An unlimited number of examples of suitable substitution groups include branched, unbranched and cyclic alkali, mono - and polycyclic arily, branched, unbranched and cyclic heteroalkyl, mono - and polycyclic heteroaryl, halogen, a branched, unbranched or cyclic halogenated, hydroxyl, oxo group, trioxo group, a branched, unbranched and cyclic alkoxy group, a branched, unbranched and cyclic halogenoalkane group, triptoreline group, a mono - or polycyclic, aryloxy group, a mono - or polycyclic, heteroaromatic groups, ethers, alcohols, sulfides, thioethers, sulfanyl (thiols), imine, isopropy, azides, amines (primary, secondary and tertiary), NITRILES (all isomers), cyanate (all isomers), thiocyanates (all isomers), nitrosourea, nitro, diazogroup, sulfoxidov, sulfonyl, sulfonic acids, sulfonamides, sulfonamides, ethers sulfamic acid, aldehydes, ketones, carboxylic acids, esters, amides, amidine, formaline, amino acids, acetylene, carbamates, lactones, lactams, glucosides, glucosuria, sulfones, ketals, acetals, thioketal, oximes, examinatio acid, esters examinavi acids, etc. and combinations of these groups. Group Sames the tion, having the functional ability of the reaction may be protected or unprotected, which is well known from previous works.

In one illustrative examples of the compounds 2,4-pyrimidinediamine according to the present invention are compounds of structural formula (I):

including their salts, hydrates, solvate and N-oxides, in which:

the structural links of the L1and L2each individually and independently from each other are selected from the group containing the direct link and the linker;

R2and R4describedbelow;

R5is selected from the group consisting of R6(C1-C6) alkyl, optionally substituted by one or more identical or different groups R8; (C1-C4) alkenyl, optionally substituted by one or more identical or different groups R8; (C2-C4) alkenyl, optionally substituted by one or more identical or different groups R8and (C2-C4) quinil, optionally substituted by one or more identical or different groups R8;

Each of the groups R6is selected independently from the group consisting of hydrogen, an electronegative group, -ORd, -SRd(C1-C3) halogenations groups, (C1-C3) perhalogenated-group, -NRcRc, halogen, (C1-C3) halogenoalkane, (C1-C3) PE is halogenoalkane, -CF3, -CH2CF3, -CF2CF3, -CN, -NC, -OCN, -SCN, -NO, -NO2, -N3,

-S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc; -S(O)2NRcRc, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)NRcRc, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)NRcRc, -C(NH)NRcRc, -OC(O)Rd, -SC(O)Rd, -OC(O)ORd, -SC(O)ORd, -OC(O)NRcRc, -SC(O)NRcRc, -OC(NH)NRcRc, -SC(NH)NRcRc, -[NHC(O)]nRd, -[NHC(O)]nORd, -[NHC(O)]nNRcRcand -[NHC(NH)]nNRcRc, (C5-C10) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8, (C6-C16) arylalkyl, optionally substituted by one or more identical or different groups R8, 5-10-membered heteroaryl, optionally substituted by one or more identical or different groups R8and 6-16-membered heteroaromatic, optionally substituted by one or more identical or different groups R8;

R8is selected from the group consisting of Ra, Rb, Ra, optionally substituted by one or more Odinak is new or different groups R aor Rb, -ORa, optionally substituted by one or more identical or different groups Raor Rb, -B(ORa)2, -B(NRcRc)2, -(CH2)m-Rb, -(CHRa)m-Rb, -O-(CH2)m-Rb,

-S-(CH2)m-Rb, -O-CHRaRb, -O-CRa(Rb)2, -O-(CHRa)m-Rb,

-O-(CH2)m-CH[(CH2)mRb]Rb, -S-(CHRa)m-Rb, -C(O)NH-(CH2)m-Rb,

-C(O)NH-(CHRa)m-Rb, -O-(CH2)m-C(O)NH-(CH2)m-Rb,

-S-(CH2)m-C(O)NH-(CH2)m-Rb, -O-(CHRa)m-C(O)NH-(CHRa)m-Rb,

-S-(CHRa)m-C(O)NH-(CHRa)m-Rb, -NH-(CH2)m-Rb, -NH-(CHRa)m-Rb,

-NH[(CH2)mRb], -N[(CH2)mRb]2, -NH-C(O)-NH-(CH2)m-Rb,

-NH-C(O)-(CH2)m-CHRbRband-NH-(CH2)m-C(O)-NH-(CH2)m-Rb;

each of the groups Raindependently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, (C4-C11) cycloalkyl, (C5-C10) aryl, phenyl, (C6-C16) arylalkyl, benzyl, 2-6-membered heteroalkyl, 3-8-membered cyclogeranyl, morpholinyl, piperazinil, homopiperazin the Nile, piperidinyl, 4-11-membered cyclohexanoltramadol, 5-10-membered heteroaryl and 6-16-membered heteroaromatic;

each of the groups Rbrepresents a suitable group which is independently selected from the group consisting of =O, -ORd(C1-C3) halogenations-group

-OCF3, =S, -SRd, =NRd, =NORd, -NRcRc, halogen, -CF3, -CN, -NC, -OCN, -SCN, -NO, -NO2, =N2, -N3, -S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)NRcRc, -C(NH)NRcRc, -C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRcRc, -OC(O)Rd, -OC(O)ORd, -OC(O)NRcRc, -OC(NH)NRcRc, -OC(NRa)NRcRc, -[NHC(O)]nRd, -[NRaC(O)]nRd, -[NHC(O)]nORd, -[NRaC(O)]nORd, -[NHC(O)]nNRcRc, -[NRaC(O)]nNRcRc, -[NHC(NH)]nNRcRcand -[NRaC(NRa)]nNRcRc;

each of the groups Rcindependently represents a protective group, or Raor alternatively, each of the groups Rctaken together with the nitrogen atom to which it is attached, with the formation of a 5-8-membered cyclogeranyl or Goethe is of aurila, which may optionally include one or more identical or different additional heteroatoms and which may optionally be substituted by one or more identical or different groups Raor suitable groups Rb;

each Rdgroup independently represents a protective group, or Ra;

each indexmindependently represents an integer from 1 to 3; and

each indexnindependently represents an integer from 0 to 3.

One of the ways to use R5is F and R6is hydrogen.

Another aspect of the present invention includes prodrugs of the compounds 2,4-pyrimidinediamine. Such prodrugs can be active in their proletarienne form or inactive until conversion to the active drug form under certain physiological or other conditions. In the prodrugs according to the present invention, one or more functional groups of the compounds 2,4-pyrimidinediamine included in percomponent (promoieties), which hatshepsuts from molecules under the conditions of application, usually by hydrolysis, enzymatic cleavage, or by some other mechanism decomposition with the formation of functional groups. For example, primary or secondary amino group can be included in amigny percomponent, which is cleaved under conditions with primary or secondary amino group. Thus, the prodrugs according to the present invention include special types of protective groups, which are called "programmy" ("progroups") and masking one or more functional groups of the compounds 2,4-pyrimidinediamine, which are under use conditions with the formation of the active drug compounds 2,4-pyrimidinediamine. The functional group included in the compounds 2,4-pyrimidinediamine, which can be masked using progroup to include in percomponent include, but are not limited to, the following: amines (primary and secondary), hydroxyl, sulfanyl (thiols), carboxy, CARBONYLS, phenols, catechol, diols, alkynes, phosphates, etc. At present we know a huge number of progroup suitable for masking these functional groups with the purpose of education percomponent able to split with the conditions of use. All these progroup, by themselves or in combinations, can be included in the prodrugs according to the present invention. Specific examples of percomponent forming a primary or secondary amino groups, which can be included in the prodrugs according to the present invention, include, but are not limited to, the following group is AMI: amides, carbamates, imine, urea, FastHenry, factorily and sullenly. Specific examples of percomponent forming sulfanilimide groups that can be included in the prodrugs according to the present invention, include, but are not limited to the following groups: thioethers, such as S-methyl derivative (montio, ditio, exitio-, iminodiacetate), Silovye the thioethers, complex thioethers, thiocarbonate, THIOCARBAMATE, asymmetric disulfides, etc. Specific examples of percomponent forming in the decomposition of hydroxyl groups that can be included in the prodrugs according to the present invention, include, but are not limited to the following groups: sulfonates, esters and carbonates. Specific examples of percomponent forming carboxyl groups that can be included in the prodrugs according to the present invention, include, but are not limited to the following groups: esters (including complex Silovye esters, ethers examinados acid and thioethers), amides and hydrazides.

In one illustrative examples of prodrugs in accordance with the present invention are compounds of structural formula (I), in which the protective group Rcand Rdis progroups.

In another illustrative example, the prodrugs according to the present invention depict ablaut a compound of structural formula (II):

including their salts, hydrates, solvate and N-oxides, in which:

R2, R4, R5, R6L1and L2represent groups that are mentioned previously in the description of formula (I);

R2bis progroups;

R4bis progroups or alkyl group, such as stands, as described later in the examples section.

Another aspect of the present invention includes compositions comprising one or more compounds and/or prodrugs according to the present invention and a suitable carrier, excipient or diluent. The exact nature of the carrier, excipient or diluent will depend upon the desired use of the composition of substances used in veterinary practice to substances used for the treatment of humans.

Another aspect of the present invention includes intermediate compounds used in the synthesis of compounds of 2,4-pyrimidinediamine and prodrugs according to the present invention. In one of the examples of intermediate compounds is represented by 4-pyrimidinamine structural formula (III):

including their salts, hydrates, solvate and N-oxides, in which R4, R5, R6and L2represent the groups mentioned previously in the description of structural formula (I); LG represents for eseau group, for example,- S(O)2Me, -SMe, or a halogen group (for example,, F, Cl, Br, I); and R4crepresents hydrogen, ProGraph, alkyl group, or another group described in this text.

In another example, intermediate compounds represented by 2-pyrimidinamine according to structural formula (IV):

including their salts, hydrates, solvate and N-oxides, in which R2, R5, R6and L1represent the groups mentioned previously in the description of structural formula (I); LG is a substituted group, such as-S(O)2Me, -SMe, or a halogen group (for example,F, Cl, Br, I).

In another example, the intermediate compound 4-amino - or 4-hydroxy-2-pyrimidinamine in accordance with structural formula (V):

including their salts, hydrates, solvate and N-oxides, in which R2, R5, R6and L1represent the groups mentioned previously in the description of structural formula (I); R7represents amino or hydroxyl group, and R2crepresents hydrogen or progroup.

In another example, intermediate compounds represented by N4-substituted cytosine in accordance with structural formula (VI):

including their salts, hydrates, solvate and N-oxides, to the which R 4, R5, R6and L2represent the groups mentioned previously in the description of structural formula (I), and R4cis a group, similar to those mentioned in the description of formula (III).

Another aspect of the present invention includes methods of synthesis of compounds of 2,4-pyridinediamine and prodrugs according to the present invention. In one example of the method involves the reaction of 4-pyrimidinamine structural formula (III) with an amine of the formula HR2cN-L1-R2where L1, R2and R2crepresent groups that are mentioned previously in the description of structural formula (IV), with the formation of 2,4-pyrimidinediamine structural formula (I), or prodrugs according to structural formula (II).

In another example, the method involves the reaction of 2-pyrimidinamine structural formula (IV) with an amine of formula R4-L2-Other4cin which L4, R4and R4crepresent groups that are mentioned previously in the description of structural formula (III), with the formation of 2,4-pyrimidinediamine structural formula (I), or prodrugs according to structural formula (II).

In another example, the method involves the reaction of 4-amino-2-pyrimidinamine structural formulas (V) (in which R7is an amino group) with an amine of formula R4-L2-Other4cin what toroi L 4, R4and R4crepresent groups that are mentioned previously in the description of structural formula (III), with the formation of 2,4-pyrimidinediamine structural formula (I), or prodrugs according to structural formula (II). Alternatively, 4-amino-2-pyrimidinamine can react with the compound of the formula R4-L2-LG, in which R4and L2represent groups that are mentioned previously in the description of structural formulas (I)and LG is replaced with the group.

In another example, the method involves the reaction of halogenation of 4-hydroxy-2-pyrimidinamine structural formulas (V) (R7is a hydroxyl group) with the formation of 2-pyrimidinamine structural formula (IV) with subsequent reaction of the specified pyrimidinamine with the appropriate amine, as described above.

In another example, the method involves the reaction of halogenation N4-substituted cytosine structural formula (VI) with the formation of 4-pyrimidinamine structural formula (III) with subsequent reaction of the specified pyrimidinamine with the appropriate amine, as described above.

The compounds 2,4-pyrimidinediamine according to the present invention are potent inhibitors of degranulation of immune cells, such as Metacity, basophils, neutrophils and/or eosinophils. Thus, another aspect of this is subramania includes methods of regulation and, in particular, inhibition of the degranulation of these cells. The proposed method consists in making degranulating cells in contact with the compound 2,4-pyrimidinediamine or prodrugs according to the present invention, or an acceptable salt, hydrate, MES, N-oxides of these compounds and/or combinations thereof in a quantity sufficient for effective regulation or inhibition of the degranulation of the cells. The method can be applied toin vitroorin vivoas treatment or prevention of diseases characterized by, caused by or associated with cell degranulation.

Not pretending to communicate with any theory to explain the principle of the available biochemical data confirm that the compounds 2,4-pyrimidinamine have an inhibiting effect on degranulation, at least in part, by blocking or inhibiting signal transduction cascades (cascades), launched as a result of crosslinking Fc receptors with high affinity for IgE (“FcεRI) receptors and/or IgG (“FcγRI”) receptors. Actually, the compounds 2,4-pyrimidinediamine are potent inhibitors of degranulation mediated and FcεRI and FcγRI receptor. As a consequence, the compounds 2,4-pyrimidine can be used for inhibition of signaling cascades specified Fc-re is atarov in the cells of all types, expressing such FcεRI and/or FcγRI receptors, including, but not limited to the following cells: macrophages, Metacity, basophils, neutrophils and/or eosinophils.

These methods also allow you to adjust and, in particular, to inhibit the processes proceeding in the forward direction, which are the result of activation of these signaling cascades Fc-receptors. Such direct processes include, but are not limited to, the following: FcεRI and/or FcγRI-mediated degranulation, cytokine production and/or production and/or secretion of lipid mediators such as leukotrienes and prostaglandins. The method generally consists in making cells of the categories described above, expressing the Fc-receptor, in contact with the compound 2,4-pyrimidinediamine or prodrugs according to the present invention or of a corresponding salt, hydrate, MES, N-oxides of these compounds and/or combinations thereof in a quantity sufficient for effective regulation or inhibition of signaling cascade Fc receptors and/or the direct process, affected by the activation of this signaling cascade. The method can be applied toin vitroorin vivoas treatment or prevention of diseases characterized by, caused by or associated with a signaling cascade Fc-receptors, such as diseases caused by the s-selection of chemical mediators of granules in the process of degranulation, the selection and/or synthesis of cytokines and/or secretion and/or synthesis of lipid mediators, such as leukotrienes and prostaglandins.

Another aspect of the present invention includes methods of treatment and/or prevention of diseases characterized by, caused by or associated with the release of chemical mediators in the activation of signaling cascades Fc-receptors, such as, for example, the signaling cascades of FcεRI and/or FcγRI receptor. These methods can be used both in animals and in humans. These methods generally consist in the introduction of an animal or human connection 2,4-pyrimidinediamine or prodrugs according to the present invention or of a corresponding salt, hydrate, MES, N-oxides of these compounds and/or combinations thereof in a quantity sufficient for effective treatment or prevention of disease. As discussed above, activation of the FcεRI signaling cascade or FcγRI receptors in certain immune cells leads to the release and/or synthesis of various chemicals that are of pharmacological mediators of a wide range of diseases. Any of these diseases can be treated or to be prevented in accordance with the methods according to the present invention.

For example, in mastocyte and basophils activation of the FcεRI signaling cascade or FcγRI receptor is in leads to an immediate ( i.e.within 1-3 min after the activation of receptors) the allocation of preformed mediators of atopic reactions and/or reactions of type I hypersensitivity (e.g., histamine, proteases, such as tryptase and so on) through the process of degranulation. Such atopic reactions and/or reactions of type I hypersensitivity include, but are not limited to, the following: anaphylactic reaction on the environment and other allergens (e.g. pollen, insect venom and/or animals, food, medications, contrast dye, etc.), anaphylactoid reactions, hay fever, allergic conjunctivitis, allergic rhinitis, allergic asthma, atopic dermatitis, eczema, hives, impaired function of the mucosa, tissues, as well as a number of gastrointestinal disorders.

Followed immediately by release of preformed mediators via degranulation results in the release and/or synthesis of other chemical mediators, including, among others, platelet activating factor (PAF), prostaglandins and leukotrienes (e.g., LTC4), andde novosynthesis and secretion of cytokines, such as TNFα, IL-4, IL-5, IL-6, IL-13, etc. the First of these two processes occurs approximately 3-30 min after activation of the receptor; and follow-up - after about 30 min to 7 h after activation of receptors. These mediators “late stage” midrange is still partially responsible for chronic symptoms above atopic reactions and hypersensitivity reactions (type I) and in addition are chemical mediators of inflammation and inflammatory diseases (i.e. osteoarthritis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, idiopathic inflammatory bowel disease, syndrome of increased irritability of the stomach, spastic colitis, etc.), poor scarring (i.e. scleroderma, pronounced fibrosis, the formation of keloids, post-surgical scars, pulmonary fibrosis, vascular spasm, migraine, reperfusion injury and post myocardial infarction) and Sjogren syndrome. All these diseases can be treated or to be prevented in accordance with the methods according to the present invention.

Additional diseases that can be treated or prevented using the methods according to the present invention include diseases associated with abnormal basophilic and/or mastocytic cells. Examples of such diseases include, but are not limited to, the following: diseases of the skin, as, for example, scleroderma, heart disease, such as myocardial infarction, pulmonary diseases, as, for example, change or conversion of the muscles of the lungs or chronic obstructive pulmonary disease (COPD), and diseases of the intestine, such as the syndrome of inflammation of the bowel (spastic colitis).

The compounds 2,4-pyrimidinediamine according to the present invention are also potent inhibitors of tyrosine kinase and, in particular, Syk kinase. Thus, another aspect of this is bretania includes methods of regulation and, in particular, inhibition of the activity of Syk kinase. The method generally consists in making Syk kinase or cells containing Syk-kinase, in contact with the compound 2,4-pyrimidinediamine or prodrugs according to the present invention or of a corresponding salt, hydrate, MES, N-oxides of these compounds and/or composition in a quantity sufficient for effective regulation or inhibition of the activity of Syk kinase. In one example of Syk-kinase presents as a dedicated or recombinant Syk kinase. In another example, Syk-kinase presents as endogenous or recombinant Syk-kinase, expressed by the cell, as, for example, in the case of mastocyte or basophil. The method can be applied toin vitroorin vivoas treatment or prevention of diseases characterized by, caused by or associated with the activity of Syk kinase.

Not trying to be limited to any one theory to explain the mechanism of action, it is believed that the compounds 2,4-pyrimidinediamine according to the present invention have an inhibiting effect on degranulation of the cells and/or release of other chemical mediators mainly due to inhibition of Syk-kinase, which is activated by the glycosilated gamma-chain receptor FcεRI (see, e.g., figure 2). This glycosilated gamma-chain is shared on the natives Fc-receptors, including FcγRI, FcγRIII and FcαRI. For all of these receptors, the process of intracellular signal transduction mediated by the General glycosilated gamma-chain. Linking and aggregation of these receptors leads to recruitment and activation tyrosinekinase, such as Syk kinase. As a result of these common signaling action, these compounds 2,4-pyrimidinediamine can be used for regulation and, in particular, inhibition of signaling cascades Fc-receptors with homodimers gamma chain, such as FcεRI, FcγRI, FcγRIII and FcαRI, and reactions of cells obtained through these receptors.

It is known that the Syk-kinase plays a critical role in other signaling cascades. For example, Syk-kinase is an effector of signal receptors of b cells (BCR) (Turneret al.,2000, Immunology Today 21:148-154) and is an essential component of the signaling pathway of beta(1)beta(2) beta(3) integrin in neutrophils (Mocsaiet al.,2002, Immunity 16:547-558). As these compounds 2,4-pyrimidinediamine are powerful inhibitors of Syk kinase, can be used for regulation and, in particular, any inhibition of signaling cascades, in which Syk-kinase plays a role, for example, in the signal cascades Fc-receptor, BCR and integrin, as well as reactions of cells obtained through these receptors. Regulation or inhibition of specific responses in cells partially hung the t from a specific cell type and signaling cascade receptors as is well known in the literature. Some examples of reactions of cells that can be adjusted or inhibition by compounds 2,4-pyrimidinediamine include respiratory burst, cell adhesion, degranulation of cells, proliferating cells, cell migration, phagocytosis (e.g.,in macrophages), the flow of calcium ions (for example, in mastocyte, basophils, neutrophils, eosinophils and B-cells), platelet aggregation and maturation of cells (such as B-cells).

Thus, another aspect of the present invention includes methods of regulation and, in particular, inhibition of signal transduction cascades involving Syk-kinase. The method generally consists in making Syk-dependent receptor or cells expressing Syk-dependent receptor into contact with the compound 2,4-pyrimidinediamine or prodrugs according to the present invention, or a corresponding salt, hydrate, MES, N-oxides of these compounds and/or combinations thereof in a quantity sufficient for effective regulation or inhibition of the signal transduction cascade. These methods can also be used for regulation and, in particular, direct inhibition of processes or reactions of cells resulting from the activation of specific Syk-dependent cascade of signal transduction. The methods of the s can be used for any regulation of signal transduction cascades, in which the role of Syk-kinase is unknown or installed at a later date. Methods can be usedin vitroorin vivoas treatment or prevention of diseases characterized by, caused by or associated with activation of Syk-dependent cascade of signal transduction. Some examples of such diseases include diseases described earlier.

The data obtained in the cell-based analysis, together with data obtained in animals, also confirm that the compounds 2,4-pyrimidinediamine in accordance with the present invention can be used for the treatment or prevention of autoimmune diseases and/or symptoms of these diseases. The appropriate methods in General comprise administration to a patient suffering from an autoimmune disease or at risk of developing an autoimmune disease, 2,4-pyrimidinediamine or prodrugs according to the present invention, or an acceptable salt, N-oxide, hydrate, MES, or combinations thereof, in amounts effective for the treatment or prevention of autoimmune disease and/or related symptoms. Autoimmune diseases amenable to treatment or prevention using the compounds 2,4-pyrimidinediamine include disease, often associated with reactions-anaphylactic hypersensitivity (II, III and/or IV ti is (a), and/or diseases mediated, at least in part, by activating FcγR signaling cascade in monocytes. Such autoimmune diseases include, but are not limited to disease, often characterized as an autoimmune disorder of a single organ or single cell type and disease, often characterized as involving systemic autoimmune disorder. Some examples of diseases, often characterized as an autoimmune disorder of a single organ or single cell type, include Hashimoto thyroiditis, autoimmune hemolytic anemia, autoimmune atrophic gastritis of pernicious anemia, autoimmune encephalomyelitis, autoimmune orchitis, syndrome?, autoimmune thrombocytopenia, sympathetic ophthalmia, asthenic bulbar paralysis, graves ' disease, primary biliary cirrhosis, chronic aggressive hepatitis, ulcerative colitis and membranous glomerulopathy. Some examples of diseases, often characterized as involving systemic autoimmune disorders include systemic lupus erythematous, rheumatoid arthritis, Sjogren syndrome, Reiter syndrome, polymyositis-dermatomyositis, systemic sclerosis, Nowotny polyarteritis, multiple sclerosis and bullous pemphigoid.

5. BRIEF DESCRIPTION of DRAWINGS

Figure 1 clearly illustratedproduce IgE under the influence of allergens and the subsequent allocation preformed and other chemical mediators of mastocytes;

Figure 2 illustrates the signal transduction cascade of FcεR1 receptors, leading to degranulation of mastocytes and/or basophils; and

Figure 3 illustrates the proposed areas of action of compounds that selectively inhibit FcεRI mediated by the receptors degranulation in the opposite direction, as well as compounds that inhibit the degranulation mediated FcεRI receptors, and degranulation caused by ionomycin.

6. DETAILED DESCRIPTION of PREFERRED embodiments of the INVENTION

6.1 Definition

For the purposes of this text, the following terms have the following meanings.

Alkyl” alone or as part of another connection refers to a saturated or unsaturated monovalent hydrocarbon radical is branched, unbranched or cyclic structure and an agreed number of carbon atoms (for example,, C1-C6 means the number of carbon atoms of from one to six), obtained by division of one hydrogen atom from a single carbon atom of the original alkane, alkene or alkyne. Typical alkyl groups include, but are not limited to, the following: methyl; ately, as, for example, etanol, ethynyl, ethinyl; cuts, as, for example, propane-1-yl, propan-2-yl, cyclopropane-1-yl, prop-1-EN-1-yl, prop-1-EN-2-yl, prop-2-EN-1-and is, cycloprop-1-EN-1-yl; cycloprop-2-EN-1-yl, prop-1-Jn-1-yl, prop-2-in-1-yl, etc.; butyl, such as butane-1-yl, butane-2-yl, 2-methyl-propane-1-yl, 2-methyl-propane-2-yl, cyclobuta-1-yl, but-1-EN-1-yl, but-1-EN-2-yl, 2-methyl-prop-1-EN-1-yl, but-2-EN-1-yl, but-2-EN-2-yl, buta-1,3-Dien-1-yl, buta-1,3-Dien-2-yl, cyclobuta-1-EN-1-yl, cyclobuta-1-EN-3-yl, cyclobuta-1,3-Dien-1-yl, but-1-in-1-yl, buta-1-in-3-yl, but-3-in-1-yl and so on; and the like. Assuming the specified saturation levels, uses the term “alkenyl”, “alkenyl” and/or “quinil”as specified below. In preferred variants of the invention, the alkyl groups are (C1-C6) alkyl.

Alkenyl” alone or as part of another connection refers to a saturated branched alkyl, unbranched or cyclic structure obtained by division of one hydrogen atom from a single carbon atom alkane source. Typical alkaline groups include, but are not limited to, the following: methanol; etenil; propanil, such as propan-1-yl, propan-2-yl (isopropyl), cyclopropane-1-yl, etc.; butonly, such as butane-1-yl, butane-2-yl (second-butyl), 2-methyl-propane-1-yl (isobutyl), 2-methyl-propane-2-yl (tert-butyl), CYCLOBUTANE-1-yl and so on; and the like. In preferred embodiments of the invention alkaline groups are (C1-C6) alkenyl.

lceil ” alone or as part of another connection refers to unsaturated alkyl branched, unbranched or cyclic structure having at least one double carbon-carbon bond, obtained by division of one hydrogen atom from a single carbon atom of the original alkene. The group may haveCIS-orTRANSthe configuration in the vicinity of the double bond (double bonds). Typical alkeneamine groups include, but are not limited to, the following: ethynyl; propenyl, such as prop-1-EN-1-yl, prop-1-EN-2-yl, prop-2-EN-1-yl, prop-2-EN-2-yl, cycloprop-1-EN-1-yl; cycloprop-2-EN-1-yl; butenyl, as, for example, but-1-EN-1-yl, but-1-EN-2-yl, 2-methylprop-1-EN-1-yl, but-2-EN-1-yl, but-2-EN-2-yl, buta-1,3-Dien-1-yl, buta-1,3-Dien-2-yl, cyclobuta-1-EN-1-yl, cyclobuta-1-EN-3-yl, cyclobuta-1,3-Dien-1-yl and so on; and the like. In preferred embodiments of the invention alkeneamine groups represent a (C2-C6) alkenyl.

Quinil” alone or as part of another connection refers to unsaturated alkyl branched, unbranched or cyclic structure having at least one triple carbon-carbon bond, obtained by division of one hydrogen atom from a single carbon atom source alkyne. Typical alkyline groups include, but are not limited to trail the who: ethinyl; propinyl, such as prop-1-Jn-1-yl, prop-2-in-1-yl, etc.; routinely, such as but-1-in-1-yl, but-1-in-3-yl, but-3-in-1-yl and so on; and the like. In preferred embodiments of the invention Alchemilla group represent a (C2-C6) quinil.

Alkerdeel” alone or as part of another connection refers to a saturated or unsaturated divalent hydrocarbon group, branched, unbranched or cyclic structure and an agreed number of carbon atoms (ieC1-C6 means the number of carbon atoms of from one to six), obtained by division of one hydrogen atom from each of two different carbon atoms of the original alkane, alkene or alkyne, or by the separation of two hydrogen atoms from a single carbon atom of the original alkane, alkene or alkyne. Two center monovalent radicals or each valency of the Central divalent radical can form a connection with the same or different atoms. Typical alkylguanine groups include, but are not limited to, the following: meander; atillery, such as ethane-1,1-diyl, ethane-1,2-diyl, ethen-1,1-diyl, ethen-1,2-diyl; propellery, such as propane-1,1-diyl, propane-1,2-diyl, propane-2,2-diyl, propane-1,3-diyl, cyclopropane-1,1-diyl, cyclopropane-1,2-diyl, prop-1-EN-1,1-diyl, prop-1-EN-1,2-diyl, prop-2-EN-1,2-diyl, prop-1-EN-1,3-diyl, C is coprop-1-ene-1,2-diyl, cycloprop-2-EN-1,2-diyl, cycloprop-2-ene-1,1-diyl, prop-1-Jn-1,3-diyl etc.; boutillier, such as butane-1,1-diyl, butane-1,2-diyl, butane-1,3-diyl, butane-1,4-diyl, butane-2,2-diyl, 2-methyl-propane-1,1-diyl, 2-methyl-propane-1,2-diyl, CYCLOBUTANE-1,1-diyl; CYCLOBUTANE-1,2-diyl, CYCLOBUTANE-1,3-diyl, buta-1-ene-1,1-diyl, buta-1-ene-1,2-diyl, buta-1-ene-1,3-diyl, buta-1-ene-1,4-diyl, 2-methyl-prop-1-EN-1,1-diyl, 2-methylidene-propane-1,1-diyl, buta-1,3-diene-1,1-diyl, buta-1,3-diene-1,2-diyl, buta-1,3-diene-1,3-diyl, buta-1,3-Dien-1,4-diyl, cyclobuta-1-ene-1,2-diyl, cyclobuta-1-ene-1,3-diyl, cyclobuta-2-EN-1,2-diyl, cyclobuta-1,3-diene-1,2-diyl, cyclobuta-1,3-diene-1,3-diyl, but-1-Jn-1,3-diyl, but-1-in-1,4-diyl, buta-1,3-Dien-1,4-diyl etc; and the like. Assuming the specified saturation levels, uses the term “alkerdeel”, “alkerdeel” and/or “alkindi”. If it is assumed that involved two valence of one and the same carbon atom, uses the term "alkylidene". In preferred embodiments of the invention ascidiella group represents a (C1-C6) alkerdeel. Preferred saturated acyclic alkanolamine group, in which the centers of the radicals are in extreme carbon atoms,for example,meander (methane), ethane-1,2-diyl (ethane-); propane-1,3-diyl (LPG); butane-1,4-diyl (butane); and the like (also referred to as alkylene which are definedbelow).

” alone or as part of another connection refers to an unbranched saturated or unsaturated alkylamines group with two extreme centers monovalent radical obtained by division of one hydrogen atom from each of two outermost carbon atoms, unbranched original alkane, alkene or alkyne. The designation of a double or triple bond, if it exists, in a separate alkylen group are shown in brackets. Typical alkylene groups include, but are not limited to, the following: methane; ethylene group, as, for example, ethane-, Aten, Aten-; propylene group, as, for example, propane, prop[1]Yong-, disappear[1,2]diene, prop[1]in etc.; butylene group, as, for example, butane-, bout[1]Yong-bottles[2]Yong-, buta[1,3]diene, bout[1]in-, bout[2]in-, buta[1,3]Dion - and so on; and the like. Assuming the specified saturation levels, uses the term “alkane-,” “alkene” and/or “alkyne-”. In preferred embodiments of the invention group alkylen represents a (C1-C6)- or (C1-C3) alkylene. Also preferred unbranched saturated alkane groups, for example methane-, ethane-, propane-, butane and the like.

"Heteroalkyl","heteroalkyl","heteroalkyl", "heteroalkyl", "heteroalkyl" and "heteroalkyl" by themselves or as part of other compounds belong to the group of Akilov, al is anilov, alkenyl, alkinyl, ALCALDIA or alkylene respectively, in which one or more carbon atoms independently of each other replaced by identical or different heteroatoms or heteroatomic groups. Typical heteroatoms and/or heteroatomic groups which can replace the carbon atoms include, but are not limited to, the following: -O-, -S-, -S-O-, -NR'-, -PH-, -S(O)-, -S(O)2-, -S(O) NR'-, -S(O)2NR' -, and the like, including combinations thereof, where each R' radical is independently a hydrogen atom or (C1-C6) alkyl group.

"Cycloalkyl" and "heteroseksualci" alone or as part of another compounds are cyclic versions of "alkyl"and "heteroalkyl"groups, respectively. If heteroalkyl group, a heteroatom can occupy the position in which it adjoins the rest of the molecule. A typical group of cycloalkyl include, but are not limited to, the following: cyclopropyl; cyclobutyl, as, for example, cyclobutenyl and cyclobutenyl; cyclopentyl, as, for example, cyclopentenyl and cyclopentenyl; cyclohexyl, as, for example, cyclohexanol and cyclohexane; and the like. A typical group of heterocyclization include, but are not limited to, the following: tetrahydrofuranyl (for example,, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl and so on), piperidinyl (for example,, piperidine-1-yl, n is piridin-2-yl and so on), morpholinyl (for example,, morpholine-3-yl, morpholine-4-yl and so on), piperazinil (for example,, piperazine-1-yl, piperazine-2-yl, etc. and the like.

"Acyclic heteroatomic bridge" refers to a divalent bridge in which the main chain atoms are exclusively heteroatoms and/or heteroatomic groups. Typical acyclic heteroatomic bridges include, but are not limited to, the following: -O-, -S-, -S-O-, -NR'-, -PH-, -S(O)-, -S(O)2-, -S(O) NR'-, -S(O)2NR' -, and the like, including combinations thereof, where each R' radical is independently a hydrogen atom or (C1-C6) alkyl group.

"The original aromatic ring system" refers to an unsaturated cyclic or polycyclic ring system having a conjugated π-electron system. In the definition of "original aromatic ring system" is specifically included a condensed ring system in which one or more rings are aromatic and one or more rings are saturated or unsaturated, such as, for example, fluorene, indan, inden, finale, tetrahydronaphthalen etc. Typical source of aromatic ring systems include, but are not limited to, the following: aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysin, corona, fluoranthene, fluorene, exact, hexagen hexalen, indocin,s-indocin, indan, inden, naphthalene, octazen, octave, octalene, oval, Penta-2,4-diene, pentacene, pentalene, Pentagon, fixed, finale, phenanthrene, pizen, pleiadene, pyrene, pesantren, Rubicon, tetrahydronaphthalen, triphenylene and the like, as well as various hidroizolare of these compounds.

"Aryl" alone or as part of another connection refers to a monovalent aromatic hydrocarbon group with a prescribed number of carbon atoms (for example,, C5-C15 represents the number of carbon atoms from 5 to 15), obtained by division of one hydrogen atom from a separate carbon atom of the original aromatic ring system. Typical aryl groups include, but are not limited to the following: group derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, Exacta, hexagen, hexylene and Indiana, Indiana, indane, indene, naphthalene, octazen, octavina, octalene, evalena, Penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, pesantren, rubiana, triphenylene, Trenitalia and the like, as well as various hidroizolare of these compounds. In preferred variants of the invention, the aryl group represents a (C5-15) aryl, with the most preferred (C5-C10) structure. The most preferred Allami are cyclopentadienyl, phenyl and naphthyl.

"Arylaryl" alone or as part of another connection refers to a monovalent hydrocarbon group obtained by division of one hydrogen atom from a separate carbon atom of the ring system in which two or more identical or non-identical initial aromatic ring systems are linked directly to each other via a single bond, in which the number referred to direct ring compounds is one less than the number of the original aromatic ring systems. Typical aryl-aryl groups include, but are not limited to, the following: biphenyl, triphenyl, phenyl-naphthyl, binaphthyl, biphenyl-naphthyl and the like. If aryl-aryl group has the specified number of carbon atoms, this number refers to the carbon atoms constituting each of the original aromatic ring. For example, (C5-C15) arylaryl represents an aryl-aryl group, in which each aromatic ring consists of 5 to 15 carbon atoms,for example,biphenyl, triphenyl, binaphthyl, venilated etc. it is Preferable that each of the original aromatic ring system, aryl-aryl groups was independent (C5-C15) aromatic system, more preferably (C5-C10) aromatic system. is also preferred are the aryl-aryl group, in which all of the original aromatic ring system are identical,for example,biphenyl, triphenyl, binaphthyl, trileptal etc.

"Biaryl" alone or as part of another connection refers to aryl-aryl group having two identical original aromatic ring system, which are connected directly with each other via a single bond. Typical burilnye groups include, but are not limited to, the following: biphenyl, binaphthyl, bentall and the like. Preferably, the aromatic ring system represented (C5-C15) aromatic ring, more preferably (C5-C10) aromatic ring. Particularly preferably, beilina group represented biphenyl.

"Arylalkyl" alone or as part of another connection refers to an acyclic alkyl group in which one of the hydrogen atoms associated with carbon atom, typically a terminal orsp3carbon atom, a substituted aryl group. Typical arylalkyl groups include, but are not limited to, the following: benzyl, 2-Penilaian-1-yl, 2-Penilaian-1-yl, naphthylmethyl, 2-Nettleton-1-yl, 2-naphthalate-1-yl, naphthalenyl, 2-naphthenate-1-yl and the like. In the case of alkyl compounds of the following terms are used: arylalkyl, arylalkyl and/or arylalkyl. In prepact the positive variants of the invention kilakila the group represents (C6-C21) arylalkyl, for example,, alonely, alkanniny or alkynylaryl fragment arylalkyl group represents a (C1-C6) structure, and aryl fragment - (C5-C15) structure. In the most preferred embodiments of the invention arylalkyl group is (C6-C13) structure,for example,, alonely, alkanniny or alkynylaryl fragment arylalkyl group is (C1-C3) structure, and aryl fragment - (C5-C10) structure.

"Source heteroaromatic ring system" refers to the original aromatic ring system in which one or more carbon atoms independently from each other substituted by the same or different heteroatoms or heteroatomic groups. Typical heteroatoms or heteroatomic groups replace the carbon atoms include, but are not limited to, the following: N, NH, P, O, S, S(O), S(O)2, Si, etc. In the definition of "source heteroaromatic ring systems" are specifically included a condensed ring system in which one or more rings are aromatic and one or more rings are saturated or unsaturated, such as, for example, benzodioxan, benzofuran, chroman, chrome, indole, indoline, Xanten, etc. In the definition of "source heteroaromatic ring system" also includes the famous ring containing General group substitution, as, for example,benzopyran and 1-methyl-1,2,3,4-tetrazol. From the definition of "original heteroaromatic ring systems" are specifically excluded benzene ring condensed with the formation of cyclic alkylene glycols, such as cyclic glycol. Typical source heteroaromatic ring systems include, but are not limited to, the following: acridine, benzimidazole, benzisoxazole, benzodioxan, benzodioxole, benzofuran, benzopyran, benzothiadiazole, benzothiazole, benzotriazole, benzoxazin, benzoxazol, benzoxazolyl, carbazole, β-carboline, chroman, chrome, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochroman, isoindole, isoindoline, isoquinoline, isothiazol, isoxazol, naphthiridine, oxadiazol, oxazol, pyrimidin, phenanthridine, phenanthroline, fenesin, phthalazine, pteridine, purine, Piran, pyrazin, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, hinzelin, quinoline, hemolysin, cinoxacin, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and the like.

"Heteroaryl" alone or as part of another connection refers to a monovalent heteroaromatic group with a prescribed number of ring atoms (for example,, "5 to 14-membered" means the number of ring atoms from 5 to 14), obtained by division of one hydrogen atom from a separate atom source heteroa the case of the ring system. Typical heteroaryl groups include, but are not limited to, the following: groups derived from acridine, benzimidazole, benzisoxazole, benzodioxane, benzodioxole, benzofuran, benzopyrone, benzothiadiazole, benzothiazole, benzotriazole, benzoxazine, benzoxazole, benzoxazolone, carbazole, β-carboline, chromane, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochroman, isoindole, isoindoline, isoquinoline, isothiazole, isoxazol, naphthiridine, oxadiazole, okesola, pyrimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, Piran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, heatline, quinoline, hemolysin, cinoxacin, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and the like, as well as various gidroizolov of these compounds. In preferred variants of the invention, the heteroaryl group is a 5 to 14-membered heteroaryl, while most preferred is a 5-10-membered heteroaryl.

"Heteroaryl-heteroaryl" alone or as part of another connection refers to a monovalent heteroaromatic group, obtained by division of one hydrogen atom from a separate atom of the ring system, in which the OI two or more identical or non-identical source heteroaromatic ring system directly connected to each other by a single bond, in which the number of such direct ring compounds is one less than the number employed source heteroaromatic ring systems. Typical heteroaryl-heteroaryl groups include, but are not limited to, the following: bipyridyl, trapidil, pyridylmethyl, bipyridyl etc. for a given number of atoms these numbers refer to the number of atoms in each of the source heteroaromatic ring systems. For example, a 5 to 15-membered heteroaryl-heteroaryl is heteroaryl-heteroaryl group in which each of the original heteroaromatic ring systems consists of 5-15 atoms,for example,bipyridyl, trapidil etc. it is Preferable that each source heteroaromatic ring system represented independent 5-15 membered heteroaromatic system, preferably 5-10-membered heteroaromatic system. Also preferred heteroaryl-heteroaryl group in which all source heteroaromatic ring system are identical.

"Bilateral" alone or as part of another connection refers to heteroaryl-heteroaryl group comprising two identical source heteroaromatic ring system, connected directly to each other by a single bond. Typical bilaterally the s groups include, but not limited to, the following: bipyridyl, biphenyl, beginline and the like. Preferably heteroaromatic ring system represented a 5 to 15-membered heteroaromatic ring, more preferably 5-10-membered heteroaromatic ring.

"Heteroaromatic" alone or as part of another connection refers to an acyclic alkyl group in which one of the hydrogen atoms associated with carbon atom, typically a terminal or orsp3carbon atom, a substituted heteroaryl group. In the case of alkyl compounds use heteroarylboronic", "heteroaromatic" and/or "heteroarylboronic". In preferred embodiments of the invention heteroallyl group represents 6-21-membered heteroaromatic,for example,, alonely, alkanniny or alkynylaryl fragment of heteroallyl represents alkyl with the structure of (C1-C6), and heteroaryl fragments - 5 to 15-membered heteroaryl. In the most preferred embodiments of the invention heteroallyl is a 6 to 13-membered heteroaromatic,for example,, alonely, alkanniny or alkynylaryl fragment of heteroallyl represents alkyl with the structure of (C1-C3), and heteroaryl fragment - 5-10-membered heteroaryl.

"Halogen" and and " halo" alone or as part of another connection in General belong to the group of fluorine, chlorine, bromine and iodine.

"Halogenated" alone or as part of another connection refers to an alkyl group in which one or more hydrogen atoms are replaced by halogen. Thus, the term "halogenated" means monohalogenated, dihalogenoalkane, trihalogen etc., including perhalogenated. For example, the expression "(C1-C2) halogenated" includes vermeil, deformity, trifluoromethyl, 1-foretel, 1,1-dottorati, 1,2-dottorati, 1,1,1-triptorelin, perforated etc.

The above groups may include prefixes and/or suffixes, which are widely used to create additional well-known alternative bands. For example, "alkyloxy" or "alkoxy" refers to a group of the formula-OR", "alkylamine" refers to a group of the formula-other" and "dialkylamino" refers to a group of the formula-NR"R"where each R" represents an independent alkyl. As another example, halogenoalkane" or "halogenations" refers to a group of the formula-OR"', where R"' represents halogenated.

"Protective group" refers to a group of atoms which, when attached to a reactive functional group in the molecule, mask, reduce or prevent reactivity functionally the group. Typically, the protective group can be selectively removed in the process of synthesis. Examples of protective groups can be found in the book. Green and Vatsa "Protective groups in organic chemistry", 3rd edition, 1999, published by j. Wylie & Sanz, new York (Greene and Wuts,Protective Groups in Organic Chemistry, 3rdEd., 1999, John Wiley & Sons, NY), as well as in the book. Harrison and others, "A brief overview of the methods of synthetic organic"so 1-8, 1971-1996, publishing house of J. Wylie & Sanz, new York (Harrisonet al.,Compendium of Synthetic Organic Methods, Vols. 1-8, 1971-1996, John Wiley & Sons, NY). Typical amino compounds of the protective group include, but are not limited to, the following: formyl, acetyl, TRIFLUOROACETYL, benzyl, benzyloxycarbonyl (“CBZ”),tert-butoxycarbonyl ("BOC"), trimethylsilyl ("TMS"), 2-trimethylsilyl-econsultancy ("TEC"), trityl and substituted triteleia group, allyloxycarbonyl, 9-fluorenylmethoxycarbonyl ("FMOC"), nitroferricyanide ("NVOC") and the like. Representative hydroxyl protective groups include, but are not limited to, those where the hydroxyl group is acylated or alkilirovanny, as, for example, benzyl and tritely esters, and alkalemia esters, tetrahydropyranyl esters, trialkylsilyl esters (for example,group TMS or TIPPS) and allyl ethers.

"The prodrug" refers to a derivative of the active compound 2,4-pyrimidine is mine (drugs), which requires a transformation under the conditions of application, as, for example, inside the body, with the aim of identifying the active 2,4-pyrimidinediamine. Prodrugs are often, but not necessarily, pharmacologically inactive until converted into the active drug. Prodrugs are typically obtained by masking a functional group, which is part of the drug 2,4-pyrimidinediamine with the aim to activate progroup (defined below) to form percomponent, which then undergoes a transformation, such as splitting, under specified conditions with the aim of identifying functional groups and, therefore, active drugs 2,4-pyrimidinediamine. Splitting percomponent can occur spontaneously, as, for example, by hydrolysis under the influence of the catalyst or other agent, as, for example, enzyme, light, acids or bases, as well as the change or the impact of any physical parameter or environment, for example temperature. The agent may be endogenous (internal) from the point of view of applications, such as, for example, an enzyme present in the cells for which the prodrug is intended, or acidic conditions in the stomach, or it may be exogenous (externally).

A wide variety of progroup and percomponent fit is for masking functional groups in the active components, containing compounds 2,4-pyrimidinediamine to obtain prodrugs are well known in practice. For example, hydroxyl functional group can be masked as sulfonate, ester or percomponent carbonate, which can be hydrolysedin vivoobtaining a hydroxyl group. Aminecontaining functional group can be masked as an amide, carbamate, Imin, urea, phosphinyl, phosphoryl or percomponent of sulfenyl, which can be hydrolysedin vivoobtaining aminecontaining group. The carboxyl group can be masked as an ester (including Silovye esters and thioesters), percomponent amide or hydrazide, which can be hydrolysedin vivoobtaining a carboxyl group. Nitrogen protective group and nitrogen prodrugs can include lower alkyl groups, as well as amides, carbamates, etc. other typical examples of suitable progroup and corresponding percomponent are obvious to experts in this field.

"Programa" refers to the type of the protective group, which when used with the aim of masking functional groups in the active drug containing 2,4-pyrimidinediamine to form percomponent turns medication into a prodrug. Progroup usually attached to the functional group of drugs is and bylinks that can be split under specified conditions. Thus, ProGraph is the part percomponent, which is cleaved to release the functional group under specified conditions. As a specific example aminosteroid percomponent having the formula-NH-C(O)CH3that contains progroup-C(O)CH3.

"Fc-receptor" belongs to the family of molecules on the cell surface that binds the Fc portion of immunoglobulin (containing specific constant region). Each Fc-receptor binds immunoglobulin specific type. For example, Fcα receptor (“FcαR”) binds IgA, FcεR-receptor binds IgE, and FcγR receptor binds IgG.

Family FcαR includes polymeric Ig receptor involved in epithelial migration IgA/IgM, melody specific RcαRI-receptor (also referred to as CD89), Fcα/µR-receptor and at least two alternative IgA receptor (as a recent review see Monteiro and van de Winkel, 2003, Annual review of immunology, advanced electronic publishing (Monteiro &van de Winkel, 2003, Annu. Rev. Immunol, advanced e-publication)). Receptor FcαRI appears on neutrophils, eosinophils, monocytes/macrophages, dendritic cells and copperbeech cells. FcαRI includes one alpha chain and FcR gamma-glycosilated, which nestmates activation (ITAM) in the cytoplasmic domain and phosphorylates Syk-kinase.

Family FcεR includes two types of receptors: named FcεRI and FcεRII (also known as CD23). FcεRI is a receptor with high affinity (binds IgE with an affinity of about 1010M-1), which is found on mastocyte, basophilic and eosinophilic cells that attach Monomeric IgE to the cell surface. FcεRI has one alpha chain, one of the beta chain and glycosilated gamma chain discussed above. FcεRII is a receptor with low affinity, ekspressirovannoj on mononuclear phagocytes, B-lymphocytes, eosinophils and platelets. FcεRII is a single polypeptide chain and does not contain glycosilated gamma chain.

The FcγR family includes three types: named FcγRI (also known as CD64), FcγRII (also known as CD32) and FcγRIII (also known as CD16). FcγRI is a receptor with high affinity (binds IgG1 with an affinity of about 108M-1), which is found on mastocyte, basophilic, mononuclear, neutrophilic, eosinophilic, and dendritic phagocytic cells that attaches Monomeric IgG to the cell surface. FcγRI includes one alpha chain and dimer gamma chain, which is included in FcαRI and FcεRI.

FcγRII is a receptor with low affinity, expressed on neutrophils, monocytes, eosinophils, platelets and B lymphocytes. FcγRII on the et one alpha chain and does not contain glycosilated gamma chain above.

FcγRIII is a receptor with low affinity (binds IgG1 with an affinity of about 5×105M-1), expressed on NK, eosinophilic, mikrofalowe, neutrophilic cells and mastocytic. It forms one alpha chain and gamma-glycosilated, which is included in FcαRI, FcεRI and FcγRI.

Experts in this field agree that the proposed structure of the subunit and the binding properties of these various Fc receptors, as well as the types of cells that expressed by them, not fully described. The above discussion mainly reflects the current state of the question regarding these receptors (see, for example,Immunobiology: the Immune system in health and disease, 5th edition, Janway and others, 2001, Fig. 9, 30 on page 371 (Immunobiology: The Immun System in Health & Disease, 5thEdition, Janeway et al., Eds, 2001, ISBN 0-8153-3642-x, Figure of 9.30 at pp. 371)and is not intended to be limited by a multitude of signaling cascades receptors, which may be regulated components described in this application.

"Degranulation via Fc-receptor" or "degranulation due to Fc receptor"refers to degranulation that isbythe signal transduction cascade Fc-receptor-initiated crosslinking of Fc-receptor.

"Degranulation due to IgE" or "degranula the Oia through Fc εRI" refers to degranulation that isbythe signal transduction cascade IgE receptor-initiated crosslinking of IgE associated with FcεR1. Stitching can be caused by allergen-specific IgE or a multivalent binding agent, such as anti-IgE antibody. Figure 2 mastocyte and/or basophilic cells show that the FcεRI signaling cascade leading to degranulation, can be divided into two stages: inverse and direct. Reverse phase includes all the processes that occur prior to mobilization of calcium ions (shown as “Ca2+” figure 2; see also figure 3). Direct phase includes the mobilization of calcium ions and all its subsequent direct processes. Compounds that inhibit the degranulation via FcεRI, can act at any point along the signal transduction cascade, a mediator which is FcεRI. Compounds that selectively inhibit the degranulation via FcεRI in the opposite direction, act to inhibit this part of the FcεRI signaling cascade in the opposite direction from the point at which the excited mobilization of calcium ions. In cell samples of compounds that selectively inhibit the degranulation via FcεRI in the reverse direction inhibit degranulation of cells, such as Metacity or basophilic cells, which advance is described or stimulated by the allergen, typical IgE, or binding agent (such as anti-IgE antibody), but not significantly inhibit degranulation of cells that are activated or stimulated degranulation agents, bypassing FcεRI signaling pathway, such as, for example, calcium ionophor the ionomycin and A23187.

"Degranulation caused IgG" or "degranulation via FcγRI" refers to degranulation that isbythe signal transduction cascade initiated by crosslinking of IgG associated with FcγRI. Stitching can be caused by allergen-specific IgG or a multivalent binding agent, such as anti-IgG antibody or antibody fragment. As signaling cascade FcεRI, FcγRI signaling cascade in mastocyte and basophilic cells also leads to degranulation, which can be divided into the same two stages: inverse and direct. Like the degranulation via FcεRI, compounds that selectively inhibit the degranulation through FcγRI in the opposite direction, operate in the opposite direction from the point at which the excited mobilization of calcium ions. In cell samples of compounds that selectively inhibit the degranulation through FcγRI in the opposite direction, inhibit the degranulation of cells, such as Metacity or basophilic cells that are activated or stimulated and lergen-specific IgG, or binding agent (such as anti-IgG antibody or its fragment), but not significantly inhibit the degranulation of cells that are activated or stimulated degranulation agents, bypassing FcγRI signaling pathway, such as, for example, calcium ionophores of ionomycin and A23187.

"Degranulation caused by iodoform" or "degranulation by ionophore" refers to degranulation of the cells, such as mastif or basophilic cell that appears when exposed to such ionophor calcium, such as ionomycin or A23187.

"Syk-kinase" refers to the well-known tyrosinekinase protein of spleen preceptor 72 kDa (cytoplasmic), expressed in B-cells and other hematopoietic cells. Syk-kinase consists of two consecutive consensus domains of Src-homology 2 (SH2)that are associated with phosphorylated motifs immunoreceptor based on tyrosine (“ITAM”), linker domains and catalytic domains (review of the structure and function of Syk-kinase are shown in Sadaet al., 2001, J. Biochem. (Tokyo) 130:177-186); and Turneret al., 2000, Immunology Today 21:148-154). Syk-kinase has been studied intensively as an effector of signal receptor b cells (BCR) (see above Turneret al., 2000). Syk-kinase is critical for phosphorylation of tyrosine complex proteins that regulate important pathways leading on the immunoreceptor, such as the cascades mobilization of Ca2+and mitogen activated protein kinase (MAPK) (see, e.g., figure 2) and degranulation. Syk-kinase also plays a critical role in integrin signaling in neutrophils (see, for example,Mocsaiet al.2002, Immunity 16:547-558).

As is customary in the present work, Syk-kinase includes the kinase of any species, including, but not limited to, humans, monkeys, cows, pigs, rodents, etc. that belongs to the family of Syk. This group is specifically included isoforms, splicing variants, allelic variants, mutants, both natural and artificial origin. Amino acid sequence such Syk-kinase are well known and are available in GENBANK (Bank of genetic material). Typical examples of mRNAs encoding different isoforms of human Syk kinase can be found in GENBANK under No. gi|21361552|ref|NM__003177,2|,

gi|496899|emb|Z29630,1|HSSYKPTK[496899]

gi|15030258|gb|BC011399,1|BC011399[15030258], which is included in this work as a reference.

Experienced practitioners will appreciate that the tyrosine kinase belonging to other families, can have active sites or binding pockets with three-dimensional structure similar to that of Syk. As a result of this structural similarity is considered that such kinases, referred to in this application "Syk-imitators"may serve as catalysts phosphorylation of substrates that f is stollerusa using Syk-kinase. Thus, it becomes clear that such Syk-simulators, cascades of signal transduction, which are influenced by such Syk-simulators, and biological reactions from exposure to such Syk-imitators and signaling pathways that are dependent on Syk imitators, can be adjusted and even inhibition using compounds 2,4-pyrimidinediamine described in this application.

"Signaling cascade dependent on Syk" refers to the cascade of signal transduction, which has the effect of Syk-kinase. Some examples of such signaling pathways that are dependent on Syk include FcαRI, FcεRI, FcγRI, FcγRIII, BCR and signaling cascades integrin.

The term "autoimmune disease" refers to diseases, often associated with non-anaphylactic reactions hierarchylevelname (reactions hierarchylevelname II, III and/or type IV), which are primarily the result of its own humoral and/or mediated by cells of the immune response by the patient to one or more immunogenic substance endogenous and/or exogenous nature. Such autoimmune diseases differ from diseases associated with anaphylactic reactions hierarchylevelname (type I or IgE mediated).

6.2 Connection of 2,4-pyrimidinediamine

Compounds according to the present invention are generally compounds 2,4-pyrimidinediamine correspond to the s structural formula (I):

including their salts, hydrates, solvate and N-oxides, in which:

L1and L2each independently from each other selected from the group consisting of one direct connection and one linker;

R2and R4are the groups described in the following embodiments of this invention, and examples;

R5selected from the group consisting of R6(C1-C6) alkyl, optionally substituted by one or more identical or different R8groups, (C1-C4) alkenyl, optionally substituted by one or more identical or different R8groups, (C2-C4) alkenyl optionally substituted by one or more identical or different R8groups and (C2-C4) quinil, optionally substituted by one or more identical or different R8groups;

each R6radical independently selected from the group consisting of hydrogen, an electronegative group, -ORd, -SRd(C1-C3) halogenations, (C1-C3) perhalogenated, -NRcRc, halogen, (C1-C3) halogenoalkane, (C1-C3) perhalogenated, -CF3, -CH2CF3, -CF2CF3, -CN, -NC, -OCN, -SCN, -NO, -NO2, -N3,

-S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)NR Rc, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)NRcRc, -C(NH)NRcRc, -OC(O)Rd, -SC(O)Rd, -OC(O)ORd, -SC(O)ORd, -OC(O)NRcRc, -SC(O)NRcRc, -OC(NH)NRcRc, -SC(NH)NRcRc, -[NHC(O)]nRd, -[NHC(O)]nORd, -[NHC(O)]nNRcRcand -[NHC(NH)]nNRcRc, (C5-C10) aryl, optionally substituted by one or more identical or different R8groups, phenyl, optionally substituted by one or more identical or different R8groups, (C6-C16) arylalkyl, optionally substituted by one or more identical or different R8groups, 5-10-membered heteroaryl, optionally substituted by one or more identical or different R8groups and 6-16-membered heteroaromatic, optionally substituted by one or more identical or different R8groups;

R8selected from the group consisting of Ra, Rb, Rasubstituted by one or more identical or different groups Raor Rb, -ORasubstituted by one or more identical or different groups Raor Rb, -B(ORa)2, -B(NRcRc)2, -(CH2)m-Rb, -(CHRa)m-Rb, -O-(CH2)m-Rb, -S-(CH2)m-Rb,-O-CHR aRb, -O-CRa(Rb)2,

-O-(CHRa)m-Rb,

-O-(CH2)m-CH[(CH2)mRb]Rb, -S-(CHRa)m-Rb, -C(O)NH-(CH2)m-Rb,

-C(O)NH-(CHRa)m-Rb, -O-(CH2)m-C(O)NH-(CH2)m-Rb,

-S-(CH2)m-C(O)NH-(CH2)m-Rb, -O-(CHRa)m-C(O)NH-(CHRa)m-Rb,

-S-(CHRa)m-C(O)NH-(CHRa)m-Rb, -NH-(CH2)m-Rb, -NH-(CHRa)m-Rb,

-NH[(CH2)mRb], -N[(CH2)mRb]2, -NH-C(O)-NH-(CH2)m-Rb,

-NH-C(O)-(CH2)m-CHRbRband-NH-(CH2)m-C(O)-NH-(CH2)m-Rb;

each Raindependently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl, cyclohexyl, (C4-C11) cycloalkyl, (C5-C10) aryl, phenyl, (C6-C16) arylalkyl, benzyl, 2-6-membered heteroalkyl, 3-8-membered cyclogeranyl, morpholinyl, piperazinil, homopiperazine, piperidinyl, 4-11-membered cyclohexanoltramadol, 5-10-membered heteroaryl and 6-16-membered heteroaromatic;

each Rbis a suitable group independently selected from the group consisting of =O, -ORd(C1-C3) halogenations, -OCF3, =S, -SRd, =NRd, =NORd, -NRcRchalogen, -CF3, -CN, -NC, -OCN, -SCN, -NO, -NO2, =N2, -N3,

-S(O)Rd, -S(O)2Rd, -S(O)2ORd, -S(O)NRcRc, -S(O)2NRcRc, -OS(O)Rd, -OS(O)2Rd, -OS(O)2ORd, -OS(O)2NRcRc, -C(O)Rd, -C(O)ORd, -C(O)NRcRc, -C(NH)NRcRc,

-C(NRa)NRcRc, -C(NOH)Ra, -C(NOH)NRcRc, -OC(O)Rd, -OC(O)ORd, -OC(O)NRcRc, -OC(NH)NRcRc, -OC(NRa)NRcRc, -[NHC(O)]nRd, -[NRaC(O)]nRd, -[NHC(O)]nORd, -[NRaC(O)]nORd, -[NHC(O)]nNRcRc, -[NRaC(O)]nNRcRc, -[NHC(NH)]nNRcRcand -[NRaC(NRa)]nNRcRc;

each Rcindependently represents Raor, alternatively, each Rctaken together with the nitrogen atom to which it is linked, with the formation of a 5-8-membered cyclogeranyl or heteroaryl, which may include one or more identical or different additional heteroatoms and which may be substituted by one or more identical or different groups Raor suitable groups Rb;

each Rdindependently represents Ra;

eachmindependently represents an integer from 1 to 3; and

eachnindependently researched the mo represents an integer of 0 to 3.

In the compounds of structural formula (I) L1and L2independently of one another represent a direct bond or a linker. Thus, as will be appreciated by qualified experts in this field, the substituents R2and/or R4can be connected directly with their respective nitrogen atoms, or, alternatively, distantierului from their respective nitrogen atoms by using a linker. The identity of the linker is not critical, and typical suitable linkers include, but are not limited to, (C1-C6) alkerdeel, (C1-C6) alkanes and (C1-C6) heteroalkyl, each of which may be optionally substituted by one or more identical or different R8groups, where R8corresponds, as previously defined for structural formula (I). In specific embodiments of the invention L1and L2independently from each other selected from the group consisting of one direct connection, (C1-C3) alkerdeel, optionally substituted by one or more identical or different groups Rasuitable Rbor R9groups and 1-3-membered heteroalkyl, optionally substituted by one or more identical or different groups Rasuitable Rbor R9groups, where R9selected from the group consisting of (C1-C3) alkyl, -OR a, -C(O)ORa, (C5-C10) aryl, optionally substituted by one or more identical or different Halogens, phenyl, optionally substituted by one or more identical or different Halogens, 5-10-membered heteroaryl, optionally substituted by one or more identical or different Halogens, and 6-membered heteroaryl, optionally substituted by one or more identical or different Halogens; and Raand Rbmatch, as it was previously defined for structural formula (I). Specific R9the group, which can be used to replace the L1and L2include-ORa, -C(O)ORa, phenyl, halogenfree and 4-halogenfrei, where Racorresponds, as previously defined for structural formula (I).

In another specific embodiment of the invention each of the L1and L2independently from each other selected from the group consisting of methane, ethane and propane, each of which may be optional odnosnie group, R9that was described above.

In all the above versions of the invention, the specific Ragroups that can be included in R9group selected from the group consisting of hydrogen, (C1-C6) alkyl, phenyl and benzyl.

In another specific embodiment of the invention, each of the th of L 1and L2represents a direct link, such that the compounds 2,4-pyrimidinediamine, according to the present invention correspond to the structural formula (Ia):

including their salts, hydrates, solvate and N-oxides, in which R2, R4, R5and R6correspond to those indicated above in the description of structural formula (I). Additional specific applications of the compounds 2,4-pyrimidinediamine according to the present invention set forth below.

In the first example, compounds of structural formula (I) and (Ia) L1L2, R5, R6, R8, Ra,

Rb, Rc, Rd,mandnare as described above, R2iswhere each group R31independently of the other is stands or (C1-C6) alkyl, and R4is. X is chosen from the group consisting of N and CH, Y is chosen from the group consisting of O, S, SO, SO2, SONR36, NH, NR35and NR37Z is chosen from the group consisting of O, S, SO, SO2, SONR36, NH, NR35and NR37. Each of R35independently selected from the group consisting of hydrogen and R8or, alternatively, two groups of R35related to the same carbon atom, taken together with the formation of oxo (=O), NH or NR38the group, and the other two R35groups, each independently of one another, are selected from the group consisting of hydrogen and R8. Each group R36independently selected from the group consisting of hydrogen and (C1-C6) alkyl. Each group R37independently selected from the group consisting of hydrogen and progroup. R38is selected from the group consisting of (C1-C6) alkyl and (C5-C14) aryl.

In particular, Y is O, Z is NH and X is N. R5may be a halogen and R6is hydrogen.

In the second example, compounds of structural formula (I) and (Ia) L1L2, R5, R6, R8, Ra, Rb, Rc, Rd,m,n, R35, R36, R37, R38X, Y and Z are as described above, R2iswhere each group R31independently of the other represents a methyl or (C1-C6) alkyl, and R4represents. In particular, Y is O, Z is NH and X is N. R5may be a halogen and R6represents hydrogen. In one particular case, Y is O, Z is NH, X is N and each of the groups R31represents methyl.

In the third example, compounds of structural formula (I) and (Ia) L1L2, R5, R6, Rsup> 8, Ra, Rb, Rc, Rd,m,n, R31, R35, R36, R37, R38X, Y and Z are as described above, R2representsorand R4representsorand yy is a number from 1 to 6. In particular, Y is O, Z represents NH and X represents N. R5may be a halogen, and R6represents hydrogen.

In the fourth example, the compounds of structural formula (I) and (Ia) L1L2, R5, R6, R8,

Ra, Rb, Rc, Rd,m,n, R35, R36, R37, R38X, Y and Z are as described above, R2representsorand R4representsor. Substitution in the region of the phenyl ring of R2can occur at positions 2, 3, 4, 5 or 6. In particular, Y is O, Z represents NH and X represents N. R5may be a halogen, and R6represents hydrogen.

In the fifth example, the compounds of structural formula (I) and (Ia) L1L2, R5, R6, R8, Ra, Rb, Rc, Rd,m,n, R35 , R36, R37, R38X, Y and Z are as described above, R2represents a phenyl group, twice substituted by two groups of Rband R4represents. Substitution in the region of the phenyl ring of R2can occur at positions 2,3, 2,4, 2,5, 2,6, 3,4, 3,5, 3,6, 4,5, 4,6 or 5.6 excluding the following compounds:

N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine;

N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine;

N2-(3,4-dichlorophenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine;

N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(3-fluoro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine;

N2-(3,5-dichlorophenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine and

N2-(3-chloro-4-trifloromethyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine.

In particular, Y is O, Z represents NH and X represents N. R5may be a halogen, and R6represents hydrogen. In certain cases, each of the groups Rbindependently selected from (C1-C6) alkoxy, (C1-16) alkyl, (C1-C6) perhalogenated, halogen, carboxylic acid, ester of carboxylic acid, carboxamides, sulfonamides, imidazo the s.

In the sixth example, the compounds of structural formula (I) and (Ia) L1L2, R5, R6, R8, Ra, Rb, Rc, Rd,m,n, R35, R36, R37, R38X, Y and Z are as described above, R2represents a phenyl group, three times substituted by three groups of Rband R4represents. Substitution in the region of the phenyl ring of R2can occur at positions 2,3,4, 2,3,5, 2,3,6, 2,4,5, 2,4,6, 2,5,6, 3,4,5, 3,4,6, 3,5,6 or 4,5,6 excluding the following compounds:

N2-(3-chloro-4-methoxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine;

N2-(3-chloro-4-hydroxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine and

N2-(3,5-dimethyl-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine.

In particular, Y is O, Z represents NH and X represents N. R5may be a halogen, and R6represents hydrogen. In certain cases, each of the groups Rbindependently selected from (C1-C6) alkoxy, (C1-16) alkyl, (C1-C6) perhalogenated, halogen, carboxylic acid, esters of carboxylic acids, carboxamides, sulfonamides.

In certain examples, the compounds listed in the patent applications U.S. under the registration and accommodation 10/631029 (filing date - July 29, 2003) and 10/355543 (filing date - 31 January 2003), respectively, are not included in the composition of the compounds included in the present application.

In the seventh example, the compounds of structural formula (I) and (Ia) R5, R6L1and L2are as described above, R2is selected from the group consisting of (C1-C6) alkyl, optionally substituted by one or more identical or different groups R8, (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8, cyclohexyl, optionally substituted by one or more identical or different groups R8, 3-8-membered cyclogeranyl, optionally substituted by one or more identical or different groups R8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and a 5 to 15-membered heteroaryl, optionally substituted by one or more identical or different groups R8, R4represents, R6arepresents a (C5-C10) aryl, optionally substituted by one or more identical or different groups R8or phenyl, neobyazatel is substituted by one or more identical or different groups R 8and R8represents a group described above.

In the eighth example, the compounds of structural formula (I) and (Ia) R5, R6, R8L1and L2are as described above, R2is selected from the group consisting ofandwhere each of the groups R21independently represents a halogen atom or alkyl, optionally substituted by one or more identical or different groups of a halogen, the group R22and R23individually and independently from each other represent a hydrogen atom, a methyl or ethyl group optionally substituted by one or more identical or different groups of a halogen, and R4represents (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8.

In the ninth example, the compounds of structural formula (I) and (Ia) R5, R6, R8L1and L2are as described above, R2is selected from the group consisting of (C1-C6) alkyl, optionally substituted by one or more identical or different groups R8, (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8, cyclohexyl, optionally substituted by one or more of the likeme identical or different groups R 8, 3-8-membered cyclogeranyl, optionally substituted by one or more identical or different groups R8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and a 5 to 15-membered heteroaryl, optionally substituted by one or more identical or different groups R8, R4representsor;

R35represents hydrogen or R8; and

R45represents (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8.

In the tenth example, the compounds of structural formula

R2selected from the group consisting of (C1-C6) alkyl, optionally substituted by one or more identical or different groups R8, (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8, cyclohexyl, optionally substituted by one or more identical or different groups R8, 3-8-membered cyclogeranyl, optionally substituted by one or more of the same and or different groups R 8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and a 5 to 15-membered heteroaryl, optionally substituted by one or more identical or different groups R8, R4is selected from the group consisting of hydrogen, (C1-C6) alkyl, optionally substituted by one or more identical or different groups R8, (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8, cyclohexyl, optionally substituted by one or more identical or different groups R8, 3-8-membered cyclogeranyl, optionally substituted by one or more identical or different groups R8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and a 5 to 15-membered heteroaryl, optionally substituted by one or more identical or different groups R8and R55is selected from the group consisting of (C1-C6) alkyl, optionally substituted by one or more identical or the hypoxia groups R 8, (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8, cyclohexyl, optionally substituted by one or more identical or different groups R8, 3-8-membered cyclogeranyl, optionally substituted by one or more identical or different groups R8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and a 5 to 15-membered heteroaryl, optionally substituted by one or more identical or different groups R8.

In the eleventh example, the compounds of structural formula (I) and (Ia) R5, R6, R8L1and L2are as described above, R2representsand R4is selected from the group consisting of hydrogen, (C1-C6) alkyl, optionally substituted by one or more identical or different groups R8, (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8, cyclohexyl, optionally substituted by one or more identical or different groups R8, 3-8-membered cyclogeranyl, not battelino substituted by one or more identical or different groups R 8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and a 5 to 15-membered heteroaryl, optionally substituted by one or more identical or different groups R8.

In the twelfth example, the compounds of structural formula (I) and (Ia) R5, R6, R8L1and

L2are as described above, R2representsor, R4is selected from the group consisting of hydrogen, (C1-C6) alkyl, optionally substituted by one or more identical or different groups R8, (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8, cyclohexyl, optionally substituted by one or more identical or different groups R8, 3-8-membered cyclogeranyl, optionally substituted by one or more identical or different groups R8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and 5-15-Chlenov is heteroaryl, optionally substituted by one or more identical or different groups R8and individually, a group R35represents hydrogen or a suitable group R8.

In the thirteenth example, the compounds of structural formula (I) and (Ia) R5, R6, R8L1and

L2are as described above, R2is selected from the group consisting of (C1-C6) alkyl, optionally substituted by one or more identical or different groups R8, (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8, cyclohexyl, optionally substituted by one or more identical or different groups R8, 3-8-membered cyclogeranyl, optionally substituted by one or more identical or different groups R8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and a 5 to 15-membered heteroaryl, optionally substituted by one or more identical or different groups R8, R4representsand R35represents hydrogen or a suitable group R8.

the fourteenth example, the compounds of structural formula (I) and (Ia) R 5, R6, R8L1and L2are as described above, R4represents a substituted phenyl group, substituted by identical or different groups R8and R2represents,

where “yy” = from 1 to 6. In one case, a phenyl group, R4is twice or three times substituted by identical or different groups R8and, in particular, halogen atoms. In particular, R4can be substituted in positions 3 and 4 in relation to the connection point N4 amine, in particular, halogen atoms and/or alkoxy groups.

In the fifteenth example, the compounds of structural formula (I) and (Ia) R5, R6, R8L1and

L2are as described above, R4represents a substituted phenyl group, substituted by identical or different groups R8and R2represents. In one case, a phenyl group, R4is twice or three times substituted by identical or different groups R8and, in particular, halogen atoms. In particular, R4can be substituted in positions 3 and 4 on the accession N4 amine, in particular, halogen atoms and/or alkoxy groups.

In the sixteenth example, the compounds of structural formula (I) and (Ia) R5, R6, R8L1and L are as described above, R4represents a substituted phenyl group, substituted by identical or different groups R8and R2represents. In one case, a phenyl group, R4is twice or three times substituted by identical or different groups R8and, in particular, halogen atoms. In particular, R4can be substituted in positions 3 and 4 in relation to the connection point N4 amine, in particular by halogen atoms and/or alkoxy groups.

In the seventeenth example, the compounds of structural formula (I) and (Ia) R5, R6, R8L1and

L2are as described above, R4represents a substituted phenyl group, substituted by identical or different groups R8and R2representswhere R35represents alkylalkoxy group and, in particular, is a. In one case, a phenyl group, R4is twice or three times substituted by identical or different groups R8and, in particular, halogen atoms. In particular, R4can be substituted in positions 3 and 4 in relation to the place of attachment of amine N4 specifically by halogen atoms and/or alkoxy groups.

In the eighteenth example of the connection structure of the Noi formula (I) and (Ia) R 5, R6, R8L1and L2are as described above, R4represents a substituted phenyl group, substituted by identical or different groups R8and R2representswhere R35represents an alkyl group and, in particular, is. In one case, a phenyl group, R4is twice or three times substituted by identical or different groups R8and, in particular, halogen atoms. In particular, R4can be substituted in positions 3 and 4 in relation to the place of attachment of amine N4 specifically by halogen atoms and/or alkoxy groups.

In the nineteenth example of the compounds of structural formula (I) and (Ia) R5, R6, R8L1and L2are as described above, R4representsand R2representsand, in particular, is substituted in positions 3 or 4 isoxazol. Y is selected from the group consisting of O, S, SO, SO2, SONR36, NH and NR37. Z is selected from the group consisting of O, S, SO, SO2, SONR36, NH and NR37. Each radical R35independently selected from the group consisting of hydrogen and

R8or alternatively, two R35groups associated with the same at the IOM carbon taken together with the formation of oxo (=O), NH or NR38groups, and each of the remaining two groups of R35if they are, independently from each other are selected from the group consisting of hydrogen and R8. Each group R36independently selected from the group consisting of hydrogen and (C1-C6) alkyl. Each group R37independently selected from the group consisting of hydrogen and progroup. R38is selected from the group consisting of (C1-C6) alkyl and (C5-C14) aryl.

In certain cases, R37is selected from the group consisting of aryl, arylalkyl, heteroaryl, Ra, Rb-CRaRb-O-C(O)R8, -CRaRb-O-PO(OR8)2, -CH2-O-PO(OR8)2, -CH2-PO(OR8)2, -C(O)-CRaRb-N(CH3)2, -CRaRb-O-C(O)-CRaRb-N(CH3)2, -C(O)R8, -C(O)CF3and-C(O)-NR8-C(O)R8.

In one case, Y is oxygen, Z is an NH and one or more R35radicals are alkyl group and, in particular, methyl group. In certain cases, two R35radical form heme-valkiry fragment, in particular heme-valkiry fragment, located adjacent to NH, as shown in the diagram.

In the twentieth example of the compounds of structural formula (I) and (Ia) R5, R6/sup> , R8L1and L2are as described above, R4representswhere each of R35radicals described above and, in particular, is a halogen atom such as fluorine, and R2represents a substituted phenyl group, substituted by identical or different groups R8. In one case, a phenyl group, R2is twice or three times substituted by identical or different groups R8and, in particular, halogen atoms. In particular, R2can be substituted in positions 3 and 5 on joining N2 amine specifically by halogen atoms and/or alkoxy groups.

In the twenty-first example, the compounds of structural formula (I) and (Ia) R5, R6, R8,

L1and L2are as described above, R4representswhere Y and Z are as described above and R2representsand, in particular, is substituted in positions 3 or 4 isoxazol. In one case, thirty-ninth example relative to R4the radical Y is NH and Z is an O, for example.

In the twenty-second example, compounds of structural formula (I) and (Ia) R5, R6, R8,

L1and L2meet the t described above, R4represents,orwhere R8and Rcare as described above and R2represents a phenyl group substituted in position 3 or 4 group. In one case, a group OR8, R8represents a hydrogen atom.

In the twenty-third example of the compounds of structural formula (I) and (Ia) R5, R6, R8,

L1and L2are as described above, R4representsand R2represents a substituted phenyl group which is substituted by at least two identical or different groups R8in accordance with the above. Suitable examples include compounds 340, 343, 349, 350 and 351.

In the twenty-fourth example of the compounds of structural formula (I) and (Ia) R5, R6, R8L1and L2are as described above, R4representsand R2represents.

In the twenty-fifth example of the compounds of structural formula (I) and (Ia) R5, R6, R8L1and L2are as described above, R4representsand R2represents where Y and R35are as described above. Suitable examples include compounds 368, 381, 382, 383 and 384.

In the twenty-sixth example of the compounds of structural formula (I) and (Ia) R5, R6, R8,

L1and L2are as described above, R4is selected from the group consisting of (C1-C6) alkyl, optionally substituted by one or more identical or different groups R8, (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8, cyclohexyl, optionally substituted by one or more identical or different groups R8, 3-8-membered cyclogeranyl, optionally substituted by one or more identical or different groups R8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and a 5 to 15-membered heteroaryl, optionally substituted by one or more identical or different groups R8and R2representswhere R35described above. Suitable examples include compounds 205 and 206.

In the twenty-seventh example of the compounds of structural formula (I) and (Ia)R 5, R6, R8L1and L2are as described above, R4representsand R2represents a phenyl group substituted by one or more identical groups R8. Suitable examples include compounds 328, 329, 330, 341, 553, 554, 555, 556, 559 and 560.

In the twenty-eighth example of the compounds of structural formula (I) and (Ia) R5, R6, R8L1and L2are as described above, R4is selected from the group consisting of (C1-C6) alkyl, optionally substituted by one or more identical or different groups R8, (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8, cyclohexyl, optionally substituted by one or more identical or different groups R8, 3-8-membered cyclogeranyl, optionally substituted by one or more identical or different groups R8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and a 5 to 15-membered heteroaryl, optionally substituted by one or more identical or different groups R8and R2not only is em a where Y corresponds to the above or is a group NR35and R35described above. Suitable examples include compounds 1070, 1071, 1073, 1074, 1075, 1076, 1078, 1080, 1085, 1091 and 1092.

In the twenty-ninth example of the compounds of structural formula (I) and (Ia) R5, R6, R8L1and L2are as described above, R4representswhere R2represents a substituted phenyl group, or indazole, which are substituted by one or more identical or different groups R8as explained above. Suitable examples include compounds 1251, 1252, 1253, 1254, and 1255.

In the thirtieth example, compounds of structural formula (I) and (Ia) R5, R6, R8L1and L2are as described above, R4representswhere each of the groups R35independently described above and R2represents. Suitable examples include compounds 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 1281, 1283, 1283, 1284, 1285, 1287, 1288, 1289, 1290 and 1291.

In the thirty-first example of the compounds of structural formula (I) and (Ia) R5, R6, R8,

L1and L2are as described above, R4representszrepresents hydrogen or a lower alkyl group, each of the groups Rxand Ryindependently represents a lower alkyl group or together form cycloalkyl, and Rprepresents a halogen atom or a lower alkyl group, and R2described above. Suitable examples include compounds 402, 403, 407, 408, 409 and 410.

In the thirty-second example of the compounds of structural formula (I) and (Ia) R5, R6, R8,

L1and L2are as described above, R2representsand

R4represents. Each of the groups R11and R12independently of one another selected from the group consisting of alkyl, alkoxy group, halogen, halogenoalkane group, aminoalkyl and hydroxyalkyl.

In the thirty-third example of the compounds of structural formula (I) and (Ia) R5, R6, R8,

L1and L2are as described above, R2is selected from (C1-C6) alkyl, optionally substituted by one or more identical or different groups R8, (C3-C8) cycloalkyl, optionally substituted by one or more identical or different groups R8, cyclohexyl, optionally substituted by one or more of the same or the difference is significant groups of R 8, 3-8-membered cyclogeranyl, optionally substituted by one or more identical or different groups R8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and a 5 to 15-membered heteroaryl, optionally substituted by one or more identical or different groups R8,or;

R4representsor;

R5, R6, R8, Ra, Rb, Rc, Rd,mandnare as described above.

Each of the groups R21, R22and R23independently from one another corresponds to the above and, in particular, is an alkyl group;

Each individual group, R28represents a halogen or alkoxy group;

R29represents (C1-C6) alkyl or (C3-C9) cycloalkyl;

R30represents an alkyl group or halogen;

X is selected from the group consisting of N and CH;

Y, Z, R35, R36, R 37and R38are as described above.

Each of the groups R46, R47and R48independently selected from the group consisting of hydrogen, alkyl, alkoxy group, hydroxyl, halogen, isoxazol, piperazine derivatives group, N-alkylpiperazine, morpholine-group and the CH3NHC(O)CH2O-, provided that none of the groups R46, R47and R48is not hydrogen, and that if one of the groups R46, R47or R48represents isoxazol, piperazine derivatives group, N-alkylpiperazine, morpholine group or the group CH3NHC(O)CH2O-then the rest of the group R46, R47or R48are hydrogen;

R50represents an alkyl group or -(CH2)qOH;

qis an integer from 1 to 6;

R52represents an alkyl group or substituted alkyl group;

ptakes on the values 1, 2 or 3; and

x= 1-8.

In the thirty-fourth example of the compounds of structural formula (I) and (Ia) R2, R4, R5L1and L2are as described above in accordance with structures (I) and (Ia), provided that R2is not 3,4,5-trimethoxyphenyl, 3,4,5-three(C1-C6) alkoxyphenyl or

where R21, R22and R23match the description of the groups R1, R2and R3, preveden the mu in U.S. patent No. 6235746, description of which is included as a reference. In the specific case of this first example, R21represents hydrogen, the group of halogen, straight or branched (C1-C6) alkyl, optionally substituted by one or more identical or different groups R25, hydroxyl, (C1-C6) alkoxy group, optionally substituted by one or more identical or different groups phenyl, or R25the thiol (-SH), (C1-C6) alkylthio group, optionally substituted by one or more identical or different groups phenyl, or R25, amino (-NH2), -Other26or-NR26R26; each group R22and

R23independently of one another are straight or branched (C1-C6) alkyl, optionally substituted by one or more identical or different groups R25; R25is selected from the group consisting from the group of halogen, hydroxyl, (C1-C6) alkoxy group, thiol, (C1-C6) alkylthio groups, (C1-C6) alkylamino groups and (C1-C6) dialkylamino group; and each of the groups R26independently represents a (C1-C6) alkyl, optionally substituted by one or more identical or different groups phenyl, or R25or a group-C(O)R27where R27represents (C1-C6) alkyl, optionally substituted by one or more identical or different propamidine or R 25.

In another particular example, R21represents a methoxy group, optionally substituted by one or more identical or different groups of halogen and/or R22and each of the groups R23independently of one another is stands or ethyl, optionally substituted by one or more identical or different groups of halogen.

In the thirty-fifth example of the compounds of structural formula (I) and (Ia) R5, R6, R8L1and L2are as described above;

R2represents, R4represents, R5, R6, R30, R35andxare as described above. In certain examples,xis a number from 2 to 4. In other examples, R35represents a methyl group. In additional examples R30represents chlorine, methyl or trifluoromethyl. In other examples R5represents fluorine and R6represents hydrogen.

In the thirty-sixth example 2,4-pyrimidinediamine includes compounds according to structure I and I(a), where R2is selected from the group consisting of (C1-C6) alkyl, optionally substituted by one or more identical or different groups R8, (C3-C8) cycloalkyl, not battelino substituted by one or more identical or different groups R 8, cyclohexyl, optionally substituted by one or more identical or different groups R8, 3-8-membered cyclogeranyl, optionally substituted by one or more identical or different groups R8, (C5-C15) aryl, optionally substituted by one or more identical or different groups R8, phenyl, optionally substituted by one or more identical or different groups R8and a 5 to 15-membered heteroaryl, optionally substituted by one or more identical or different groups R8. R4represents, R5, R6and R8are as described above. In the specific examples R5represents a fluorine atom, and R6represents a hydrogen atom. In certain examples R2is a twice or three times substituted phenyl group.

In the thirty-seventh example of the invention relates to compounds of 2,4-pyrimidinediamine in accordance with structural formula I and I(a), where R2representsor, R4representsand R5, R6, R22and R23, R46, R47and R48correspond described to enter the, while each of the groups R21independently of one another represents an alkyl group. In certain examples R5represents a fluorine atom, and R6represents a hydrogen atom.

In the thirty-eighth example of the present invention relates to compounds of 2,4-pyrimidinediamine in accordance with structural formula I and I(a), where R2represents

R4is

or;

R5, R6, R8, R21, R23, R28, R35, R36, R37, R38, Y, Z, Ra, Rb, Rc, Rd,mandnare as described above and X is selected from the group consisting of N and CH. In a particular example, R28represents a methoxy group. In another example, R23represents methyl. In the specific examples R21represents a methyl group. In other examples, each of the groups R28represents chlorine. In additional examples R21represents a methyl group and at least one group

R28represents chlorine. In another example, R28represents a methoxy group.

In the thirty-ninth example of the present invention provides compounds of pyrimidinediamine in with the accordance with structural formula I and I(a), where R2represents

R4isor, R5, R6, R8, R21each R28, R29, Ra, Rb, Rc, Rd,mandnX, Y, Z, each of the groups R35each of the groups R36each of the groups R37and R38are as described above.

In certain examples R29represents atert-boutelou group. In other examples, R21represents a methyl group. In certain examples, each of the groups R28represents chlorine. In an additional example, R21represents a methyl group and at least one of the groups R28represents chlorine.

In the forties example, the invention relates to compounds of 2,4-pyrimidinediamine in accordance with structural formula I and I(a), where R2represents

R4represents, R5, R6, R8, R21each of the groups R28, Ra, Rb, Rc, Rd,m,n,pX, Y, Z, each of the groups R35each of the groups R36each of the groups R37and R38are as described above. In the specific examples R21is sobiratelniye group. In other examples, each of the groups R28represents chlorine. In other examples R21represents a methyl group and at least one of the groups R28represents chlorine. In one case,ptakes on the values 1 or 2.

In the forty-first example of the invention relates to compounds of 2,4-pyrimidinediamine in accordance with structural formula I and I(a), where R2represents, R4representsor, R5, R6, R8, R21each of the groups R28, Ra, Rb, Rc, Rd,m,n,qX, Y, Z, R35, R36, R37, R38, R50and R52are as described above.

In certain cases, R50represents-CH2CH2-OH or methyl. In another case, R52represents trifluoromethyl. In one case, at least one of the groups R28represents chlorine. In one case, R50represents methyl and at least one of the groups R28represents chlorine.

In the forty-second example and with reference to the first through forty-first examples of the group R5pyrimidine ring represents a halogen atom, such as fluorine, and R6pyrimidine is oliza represents a hydrogen atom.

In the forty third example, L1and L2are covalent bonds in the examples described above.

Specifically described, the combination of the above examples of specific implementations of the present invention from the first to the forty-third.

Specialists in this field will appreciate that described in this application, the compounds 2,4-pyrimidinediamine may include functional groups that can be masked by programi in order to create prodrugs. Such prodrugs are typically, but not necessarily, not pharmacologically active up until not go into its active medicinal form. Indeed, many of the active compounds 2,4-pyrimidinediamine described in table 1, include percomponent, which are hydrolyzable or split in other ways by the conditions of use. For example, the group of ester usually undergo hydrolysis, catalyzed by acid, to obtain the original carboxylic acids, if they are in the acid environment of the stomach, or hydrolysis, catalyzed by base, if they are in the basic environment of the intestine or blood. Thus, for oral use 2,4-pyrimidinediamine, which include esters, can be considered prodrugs of the corresponding carboxylic acid, regardless of whether formaking ether pharmacologically active. Based on data from table 1, numerous 2,4-pyrimidinediamine in accordance with the present invention containing ester, active in their essential "proletarienne" form.

In the prodrugs of the present invention any of the available functional component can be masked using progroup to obtain prodrugs. Functional groups in the compounds 2,4-pyrimidinediamine that using progroup can be masked for inclusion in percomponent include, but are not limited to, the following: amines (primary and secondary), hydroxyl, sulfanyl (thiols), carboxy, etc. In the practice known countless progroup suitable for masking such functional groups to obtain percomponent, which are under the preferred conditions of use. All these progroup, separately or in combination, can be included in the prodrugs according to the present invention.

In one illustrative examples of prodrugs in accordance with the present invention are compounds corresponding to structural formula (I)in which Rcand Rdcan be progroup in addition to the previously described alternatives.

Specialists in this field will be clear that many of the compounds and prodrugs according to the present from which retenu, as different samples of the compounds specifically described and/or illustrated herein may exhibit the phenomena of tautomerism, conformational isomerism, geometric isomerism and/or optical isomerism. For example, the compounds and prodrugs according to the present invention can include one or more chiral centers and/or double bonds and, consequently, may exist as stereoisomers, such as, for example, the isomers with double bonds (i.e., geometric isomers), enantiomers and diastereoisomers and their mixtures such as racemic mixtures. As another example, consider the compounds and prodrugs according to the present invention, which can exist in several tautomeric forms including the enol form, ketoform and mixtures thereof. As different names, formulas and structures of compounds in the specification and claims can represent only one of the possible tautomeric forms, conformational isomerism, optical isomerism or geometric isomerism. It should be understood that the invention encompasses any tautomeric forms, any form of conformational isomerism, optical isomerism and/or geometric isomerism compounds or prodrugs of one or more of the advantages described herein, as well as mixtures of these various different isomeric forms. In the cases of the found rotation around the nucleus structure of 2,4-pyrimidinediamine becomes possible education atrophic isomers, also specifically included in the compounds according to the present invention.

In addition, experts in this field should understand that when included in the lists of alternative alternate members, who are due to valence or for other reasons cannot be used to replace a specific group, you should use only those members of the list, which is suitable for replacement of a particular group. For example, it is clear that while all of these alternative substituents for Rbcan be used to replace alkyl groups, some of the alternative substituents, such as =O, cannot be used to replace a phenyl group. It is necessary to consider that these are the only possible combinations of pairs of groups of deputies.

Compounds and/or prodrugs according to the present invention can be identified according to their chemical structure or chemical name. If the chemical structure and chemical name contradict each other, determining if the identification of specific compounds is a chemical structure.

Depending on the nature of the various substituents of the compounds and prodrugs of 2,4-pyrimidinediamine, the components of the invention may be in the form of salts. Such salts include salts suitable for pharmaceutical use ("pharmaceutical is Eski acceptable salts"), salts suitable for veterinary use, etc. Such salts can be derived from acids or bases, which is well known in practice.

In one example implementation of the salt is pharmaceutically acceptable. Typically, pharmaceutically acceptable salts are those salts which retain a substantial portion of one or more desirable pharmacological functions of the original component and which is suitable for administration to humans. Pharmaceutically acceptable salts include the acid additive salts formed with inorganic acids or organic acids. Inorganic acids suitable for the formation of pharmaceutically acceptable acid additive salts include, for example, but not limited to, the following: kaleidostone acid (for example,hydrochloric acid, Hydrobromic acid, uudistoodetena acid etc), sulfuric acid, nitric acid, phosphoric acid and the like. Organic acids suitable for forming pharmaceutically acceptable acid additive salts include, for example, but not limited to, the following: acetic acid, triperoxonane acid, propionic acid, hexanoic acid, cyclopentylpropionic acid, glycolic acid, oxalic acid, pyruvic acid, lactic acid, malonic acid, succinic sour is a, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, palmitic (hexadecanoyl) acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic (In-phenylacrylate) acid, mandelic acid, alkylsulfonate acid (for example,methansulfonate, econsultation, 1,2-ethane-disulfonate, 2-hydroxyethanesulfonic etc), arylsulfonate acid (for example,benzolsulfonat acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonate acid, 4-toluensulfonate), cycloalkylcarbonyl acid (for example, camphorsulfacid), 4-methylbicyclo[2,2,2]-Oct-2-ene-1-carboxylic acid, glucoheptonate acid, 3-phenylpropionate acid, trimethylhexane acid, tertiary Butylochka acid, louisanna acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic (octadecanoic) acid, Mukanova acid and the like.

Pharmaceutically acceptable salts also include salts formed by the replacement of a proton acid, present in the original compound, a metal ion (for example,, ion alkaline, alkaline earth metal or aluminum), ammonium ion or by agreement with an organic base (for example,, ethanolamine, diethanolamine, triethanol the other, N-methylglucamine, morpholine, piperidine, dimethylamine, diethylamine etc).

The compounds 2,4-pyrimidinediamine according to the present invention, as well as their salts, can be in the form of a hydrate, solvate and N-oxides, are well known in practice.

6.3 synthesis Techniques

The compounds and prodrugs of the invention under examination can be synthesized by various methods using commercially available starting materials and/or starting materials prepared with conventional synthetic methods. Various methods that can be used for the synthesis of compounds of 2,4-pyrimidinediamine and prodrugs according to the present invention, is described in U.S. patent No. 5958 935, application for U.S. patent No. 10/355543, filed January 31, 2003 (publication U.S. US20040029902-A1), the European patent WO 03/063794, published August 1, 2003, application for U.S. patent No. 10/631029 filed July 29, 2003 and the European patent WO 2004/014382, published February 19, 2004, the contents of which are incorporated in this application by reference. All compounds having structural formula (I), (Ia) and (II)can be prepared by simple modifications of these methods.

The variety of possible ways of synthesis that can be used for synthesizing compounds of 2,4-pyrimidinediamine according to the present invention, description is but below in schemes (I)to(XI). In schemes (I)-(XI) compounds with the same numbers have similar patterns. These methods are traditionally used for synthesizing the prodrugs, the corresponding structural formula (II).

In one example implementation, the compounds can be synthesized from substituted or unsubstituted orallow or thiouracil, as shown in the following scheme (I):

Scheme (I)

In scheme (I) R2, R4, R5, R6L1and L2match previous definition of structural formula (I), X represents a halogen (for example,, F, Cl, Br or I), and Y and Y'each independently from each other selected from the group consisting of O and S. on the Basis of the scheme (I), uracil or thiouracil2dehalogenase in 2 - and 4-positions using standard halogenation substances POX3(or other standard halogenation substances) under standard conditions to obtain 2,4-bangaloreindia4. Depending on the substituent R5in the pyrimidine4the halide in the C4 position is more reactive toward electron-donor substances than the halide at position C2. This difference in reactivity can be used for synthesizing 2,4-pyrimidinediamine corresponding to structural formula (I), by reaction of 2,4-bangaloreindia4with one equivalent of am is to 10producing 4N-substituted-2-halogen-4-pyrimidinamine8followed Amin6,obtaining 2,4-pyrimidinediamine corresponding to structural formula (I). 2N,4N-Bis(substituted)-2,4-pyrimidinediamine12and14can be obtained by reaction of 2,4-bangaloreindia4abundant compounds6or10respectively.

In most cases, as shown in the diagram, the halide C4 more reactive toward electron-donor substances. However, as should be clear to the experts, the properties of the substituent R5can change the reactivity. For example, if R5represents trifluoromethyl, the resulting reaction produces a mixture of 50:50 4N-substituted-4-pyrimidinamine8and the corresponding 2N-substituted-2-pyrimidinamine. Regardless of what the substituent R5the regiospecificity of the reaction can be controlled by adjusting the solvent and other synthesis conditions (such as temperature), which is well known from the practice.

The reaction illustrated in scheme (I)may proceed faster in the case of microwave heating of the reaction mixture. In this case, you can use the following conditions: heating to 175°C in ethanol for 5-20 min in the reactor Smith (production company Personal Chemistry) in a sealed tube at a pressure of 20 bar).

The original Mat is the rials uracil or thiouracil 2can be purchased commercially or prepared using standard methodology used in organic chemistry. As an example, commercial orallow and thiouracils that you can use as starting materials for the reactions according to scheme (I), you can use uracil, supplied by Aldrich (catalog No. 13,078-8;

registration number CAS 66-22-8); 2-thio-uracil (Aldrich catalog 11,558-4; registration number CAS 141-90-2); 2,4-ditional (catalog number Aldrich 15,846-1; registration number CAS 2001-93-6); 5-acetoacetyl (Chem. Sources'l 2000, registration number CAS 6214-65-9); 5-azidoethyl; 5-aminouracil (catalog number Aldrich 85,528-6; registration number CAS 932-52-5); 5-bromouracil (catalog number Aldrich 85,247-3; registration number CAS 51-20-7); 5-(TRANS-2-bromovinyl)uracil (Aldrich catalog 45,744-2; registration number CAS 69304-49-0); 5-(TRANS-2-chloride)-uracil (registration number CAS 81751-48-2); 5-(TRANS-2-carboxyvinyl)uracil; uracil-5-carboxylic acid (hydrate 2,4-dihydroxypyrimidine-5-carboxylic acid; Aldrich catalog 27,770-3; registration number CAS 23945-44-0); 5-florouracil (catalog number Aldrich 22,458-8; registration number CAS 1820-81-1); 5-cianorte (Chem. Sources'l 2000; registration number CAS 4425-56-3); 5-ethyluracil (catalog number Aldrich 23,044-8; registration number CAS 4212-49-1); 5-attaluri (registration number CAS 37107-81-6); 5-ft is rouracil (catalog number Aldrich 85,847-1; registration number CAS 51-21-8); 5-iodouracil (catalog number Aldrich 85,785-8; registration number CAS 696-07-1); 5-methyluracil (thymine; Aldrich catalog 13,199-7; registration number CAS 65-71-4); 5-nitrouracil (catalog number Aldrich 85,276-7; registration number CAS 611-08-5); uracil-5-sulfamic acid (Chem. Sources'l 2000; registration number CAS 5435-16-5); 5-(trifluoromethyl)uracil (Aldrich catalog 22,327-1; registration number CAS 54-20-6); 5-(2,2,2-triptorelin)uracil (registration number CAS 155143-31-6); 5-(pentafluoroethyl)uracil (registration number CAS 60007-38-3); 6-aminouracil (catalog number Aldrich A5060-6; registration number CAS 873-83-6); uracil-6-carboxylic acid (orotic acid; Aldrich catalog 0-840-2; registration number CAS 50887-69-9); 6-methyluracil (catalog number Aldrich D11,520-7; registration number CAS 626-48-2); uracil-5-amino-6-carboxylic acid (5-aminocrotonate acid; Aldrich catalog 19,121-3; registration number CAS #7164-43-4); 6-amino-5-nitrosourea (6-amino-2,4-dihydroxy-5-nitrosopyrimidine; Aldrich catalog 27,689-8; registration number CAS 5442-24-0); uracil-5-fluoro-6-carboxylic acid (5-torontoa acid; catalog Aldrich 42,513-3; registration number CAS 00000-00-0); and uracil-5-nitro-6-carboxylic acid (5-microanatomy acid; Aldrich catalog 18,528-0; registration number CAS 600779-49-9). Additional 5-, 6 -, and 5,6-substituted orally and/or thiouracil can be purchased in the General Intermediates of Canada, Inc., (Edmonton, PCs Alberta, Canada) (www.generalintermediates.com) and/or Interchim, France) (www.interchim.com)producing chemicals, or can be prepared using standard methodology.Belowgiven the large number of links to manuals, which set out appropriate synthetic methods.

Amines6and10can be purchased from commercial sources or, alternatively, can be synthesized using standard techniques. For example, the required amines can be synthesized from the nitro precursor, using standard chemical methods. Examples of specific reactions described in the "Examples"section. Cm. also Vogel, 1989,Practical Organic Chemistry, Addison Wesley Longman, Ltd. and John Wiley & Sons, Inc.

From practice it is known that in some cases, amines 6 and 10 and/or the substituents R5and/or R6on the uracil or thiouracil2may include functional groups that require protection during synthesis. Specific features of any protective group (s) will depend on the nature of the functional group that you want to protect, and this will be taken into account by the experts in this field. Guidance on the selection of suitable protective groups, as well as synthetic strategies for their addition and removal can be found for example in: Greene, and heard to report with glee,Protective groups in organicSint shall see, 3rd edition ed: John Wiley & sans, new York, 1999 (Greene &Wuts,Protective Groups in Organic Synthesis, 3d Edition, John Wiley & Sons, Inc., New York (1999)) and in the references mentioned hereinafter (hereinafter "green and heard to report with glee").

A specific example of implementation of the reaction scheme (I), in which the source material is 5-fluorouracil (catalog number Aldrich 32,937-1)shown below in scheme (Ia):

Scheme (Ia)

In scheme (Ia), R2, R4L1and L2consistent with their previous definition for scheme (I). According to the scheme (Ia) 5-fluorouracil3galogenidov using POCl3to obtain 2,4-dichloro-5-herperidin5which is then reacted with excess amine6or10with the receipt of N2,N4-bis-substituted 5-fluoro-2,4-pyrimidinediamine11or13respectively. Alternatively, asymmetric 2N,4N-disubstituted-5-fluoro-2,4-pyrimidinediamine9can be obtained by reaction of 2,4-d sodium dichloro-5-herperidin5with one equivalent of amine10(with the formation of 2-chloro-N4-substituted-5-fluoro-4-pyrimidinamine7), and then with one or more equivalents of amine6.

In another example of implementation of the compounds 2,4-pyrimidinediamine according to the present invention can be synthesized from substituted or unsubstituted cytosine below in schemes (IIa) and (IIb):

Schema is (IIa)

Scheme (IIb)

In schemes (IIa) and (IIb) R2, R4, R5, R6L1L2and X correspond to the previous defined for scheme (I)and PG represents a protective group. On the basis of schemes (IIa), ekzoticeski Amin C4 cytosine20first, protected by a suitable protecting group PG with the formation of N4-protected cytosine22. For specific guidance regarding protective groups used in this context,seeVorbrüggen and Ruh-Pohlenz, 2001,Handbook of Nucleoside Synthesis, John Wiley & Sons, NY, pp. 1-631. Protected cytosine22halogenous at position C2 in standard conditions using standard reagent halogenoalkane with the formation of 2-chloro-4N-protected-4-pyrimidinamine24. Reaction with amine 6, followed by removal of the protection ekzoticheskogo C4 amine and reaction with the amine10that leads to the formation of 2,4-pyrimidinediamine corresponding to structural formula (I).

Alternatively, on the basis of the scheme (IIb), cytosine20can react with the amine10or protected amine21 with the receipt of N4-substituted cytosine23or27respectively. These substituted cytosine can then be, as described above, galogenirovannyie, taken under protection (in the case of N4-substituted cytosine27) and subjected to interaction with the min 6obtaining 2,4-pyrimidinediamine corresponding to structural formula (I).

Commercially available cytosine, which can be used as starting materials in schemes (IIa) and (IIb)include, but are not limited to the above: cytosine (catalog number Aldrich 14,201-8; registration number CAS 71-30-7); N4-acetylcytosine (catalog number Aldrich 37,791-0; registration number CAS 14631-20-0); 5-ferritin (catalog number Aldrich 27,159-4; registration number CAS 2022-85-7) and 5-(trifluoromethyl)cytosine. Other suitable cytosine applicable as starting materials in schemes (IIa), can be purchased at the General Intermediates of Canada, Inc. (Edmonton, PCs Alberta, Canada)(www.generalintermediates.com)and/or Interchim, France) (www.interchim.com or prepared using standard techniques.Belowgiven a large number of links to reference guides synthetic methods for their preparation.

In another example of implementation of the compounds 2,4-pyrimidinediamine consider the invention can be synthesized from substituted or unsubstituted 2-amino-4-pyrimidinyl, as shown below in scheme (III):

Scheme (III)

In scheme (III), R2, R4, R5, R6L1L2and X correspond to their description on the scheme (I), and Z is a substituted group,belowread more consider the connection with the scheme IV. On the basis of the scheme (III), 2-amino-4-pyrimidine30reacts with the amine6(or, optionally, protected amine21) to obtain N2-substituted-4-pyrimidinone32which is then subjected to galogenirovannyie, as described above, to obtain the N2-substituted-4-halo-2-pyrimidinamine34. Additional removal protection (for example, if the protected amine21was used in the first stage), followed by reaction with amine10that leads to the formation of 2,4-pyrimidinediamine corresponding to structural formula (I). In the alternative case, pyrimidines30may react with allermuir substance31.

Suitable and commercially available 2-amino-4-pyrimidinone30that you can use as starting materials in scheme (III)include, but are not limited to, the following: hydrate 2-amino-6-chloro-4-pyrimidinone (catalog number Aldrich A4702-8; registration number CAS 00000-00-0) and 2-amino-6-hydroxy-4-pyrimidine (catalog number Aldrich A5040-1; registration number CAS 56-09-7). Other 2-amino-4-pyrimidinone 30, applicable as starting materials in scheme (III), can be purchased at the General Intermediates of Canada, Inc., (Edmonton, PCs Alberta, Canada) (www.generalintermediates.com) and/or Interchim, France) (www.interchim.com), or prepared using standard techniques.Belowgiven a large number of links to reference guides with staticheskim methods of their preparation .

In the alternative case of compound 2,4-pyrimidinediamine according to the present invention can be synthesized from substituted or unsubstituted 4-amino-2-pyrimidinone, as shown below in scheme (IV):

Scheme (IV)

In scheme (IV) R2, R4, R5, R6L1and L2meet their designations on the scheme (I)and Z represents a substitutable group. On the basis of the scheme (IV), C2-hydroxyl-4-amino-2-pyrimidinone40more reactive towards nucleophiles than the C4-amine, so that the reaction with the amine6leads to the formation of N2-substituted-2,4-pyrimidinediamine42. Subsequent reaction with the compound44that includes good substitutable group Z or Amin10that leads to the formation of 2,4-pyrimidinediamine corresponding to structural formula (I). Connection44can include almost any substitutable group which may be substituted C4-amine N2-substituted-2,4-pyrimidinediamine42. Suitable substituted groups Z include, but are not limited to, the following: halogen, methanesulfonate group (mesilate-group; "OMs"), tripterocalyx group ("OTf") andp-toluensulfonate group (tosyloxy-group; "OTs"), benzosulfimide group (mesilat"), mechanicalinternational group ("nosilec"). Other suitable for ishaemia groups are well known to specialists in this field.

Substituted 4-amino-2-pyrimidine used as starting material may be obtained commercially or synthesized using standard techniques.Belowgiven a large number of links to reference guides synthetic methods for their preparation.

In yet another example implementation of the compounds 2,4-pyrimidinediamine according to the present invention can be obtained from 2-chloro-4-aminopyrimidine or 2-amino-4-chloropyrimidine, as shown below in scheme (V):

Scheme (V)

In scheme (V), R2, R4, R5, R6L1L2and X represent previously described in scheme (I), and Z corresponds to its designation in the diagram (IV). On the basis of the scheme (V), 2-amino-4-chloropyrimidine50reacts with the amine10with the formation of 4N-substituted-2-pyrimidinamine52which, following reaction with the connection31or Amin6forms 2,4-pyrimidinediamine corresponding to structural formula (I). In the alternative case 2-chloro-4-aminopyrimidine54may react with compound44and then with an amine to obtain the compounds corresponding to structural formula (I).

Examples of commercially available starting materials for use in scheme (V) include, but are not limited to varieties of pyrimidines50 and54including 2-amino-4,6-dichloropyrimidine (catalog number Aldrich A4860-1; registration number CAS 56-05-3); 2-amino-4-chloro-6-methoxypyridazine (catalog number Aldrich 51,864-6; registration number CAS 5734-64-5); 2-amino-4-chloro-6-methylpyrimidin (catalog number Aldrich 12,288-2; registration number CAS 5600-21-5); and 2-amino-4-chloro-6-methylthiopyrimidine (catalog number Aldrich A4600-5; registration number CAS 1005-38-5). Additional source material on the basis of pyrimidine can be purchased in the General Intermediates of Canada, Inc. (Edmonton, PCs Alberta, Canada) (www.generalintermediates.com) and/or Interchim, France) (www.interchim.com or prepared using standard methodology.Belowgiven a large number of links to reference guides synthetic methods for their preparation.

In the alternative case of 4-chloro-2-pyrimidinamine50can be prepared as shown below in scheme (Va):

Scheme (Va)

In the diagram (Va) R5and R6correspond to the designations in the structural formula (I). In the diagram (Va) dicarbonyl53reacts with guanidine obtaining 2-pyrimidinamine51. The reaction nagkakamali type m-chloroperbenzoic acid, cryptocercus acid or a complex of hydrogen peroxide with urea leads to the formation of N-oxide55that then halogenous to obtain 4-chloro-2-pyrimidinamine5 . The corresponding 4-halo-2-pyrimidinamine can be obtained by using a suitable halogenation agents.

In yet another example implementation of the invention compounds 2,4-pyrimidinediamine according to the present invention can be prepared from substituted or unsubstituted of uridines, as shown below in scheme (VI):

Scheme (VI)

In scheme (VI), R2, R4, R5, R6L1L2and X correspond to the designations on the scheme (I), and the upper index PG represents a protective group, considered in connection with the scheme (IIb). According to the scheme (VI), uridine60has such a reactive center C4 that the reaction with the amine10or protected amine21leads to the formation of N4-substituted cytidine62or64respectively. Removing protection from N4-substituted62or64using an acid catalyst (when "PG" represents the acid-unstable protective group) gives N4-substituted cytosine28that can then be galogenidov in the C2-position and subjected to interaction with the amine 6 with obtaining 2,4-pyrimidinediamine corresponding to structural formula (I).

In the same way as the source material can also be used cytidine, as shown below in scheme (VII):

Scheme (VII)

In scheme (VII), R2R 4, R5, R6L1L2and X correspond to the designations on the scheme (I), and the upper index PG represents a protective group as mentioned above. On the basis of the scheme (VII), like uridine60citizen70has such a reactive center C4 that the reaction with the amine10or protected amine 21 leads to the formation of N4-substituted cytidine62or64respectively. These cytidine62and64then processed as described above for scheme (VI), with 2,4-pyrimidinediamine corresponding to structural formula (I).

Although schemes (VI) and (VII) are described as an example with robotersysteme, an experienced specialist in this field it is clear that you can use corresponding 2'-deoxyribo - and 2',3'-dideoxynucleoside, as well as nucleosides, including sugar or analogues of sugars, which differs from ribose.

Numerous uridine and cytidine suitable for use as starting material in schemes (VI) and (VII), known in the art and include, for example, and without limitation, 5-trifluoromethyl-2'-deoxycytidine (Chem. Sources, No. ABCR F07669; registration number CAS 66,384-66-5); 5-bromouridine (Chem. Sources'l 2000, registration number CAS 957-75-5); 5-iodine-2'-deoxyuridine (catalog number Aldrich 1-775-6; registration number CAS 54-42-2); 5-ferritin (catalog number Aldrich 32,937-1; registration number CAS 316-46-1); -iodouridine (catalog number Aldrich 85,259-7; registration number CAS 1024-99-3); 5-(trifluoromethyl)uridine (Chem. Sources'l 2000; registration number CAS 70-00-8); 5-trifluoromethyl-2'-deoxyuridine (Chem. Sources'l 2000; registration number CAS 70-00-8). Additional uridine and cytidine that can be used as a starting material in schemes (VI) and (VII), can be purchased at the General Intermediates of Canada, Inc. (Edmonton, PCs Alberta, Canada) (www.generalintermediates.com) and/or Interchim, France) (www.interchim.com or prepared using standard methodology.Belowgiven a large number of links to reference guides synthetic methods for their preparation.

The compounds 2,4-pyrimidinediamine according to the present invention can also be synthesized from substituted pyrimidines, such as chlorine substituted pyrimidines, as shown below in schemes (VIII) and (IX):

Scheme (VIII)

Scheme (IX)

In the diagrams (VIII) and (IX) R2, R4L1L2and Racorrespond to the designations in the structural formula (I), and "Ar" represents an aryl group. On the basis of the scheme (VIII), the reaction of 2,4,6-trichloropyridine80(catalog number Aldrich T5,620-0; CAS No. 3764-01-0) with the amine6leads to the formation of a mixture of three compounds: substituted pyrimidine mono-, di - and triamino81, 82and83that can be separated and the separation of the s using high-performance liquid chromatography (HPLC) or other conventional techniques. Mono - and diamines81and82can further react with amines6and/or10with the formation of N2,N4,N6-triple-substituted-2,4,6-pyrimidinediamine84and85respectively.

N2,N4-bis-substituted-2,4-pyrimidinediamine can be prepared in a manner analogous shown in scheme (VIII), using as starting materials 2,4-dichloro-5-methylpyrimidin or 2,4-dichloropyrimidine. In this case, one-deputizing pyrimidinamine corresponding to the connection81that is not formed. Instead, the reaction takes place direct formation of N2,N4-bis-substituted-2,4-pyrimidinediamine.

On the basis of the scheme (IX), 2,4,5,6-tetrachloropyridine90(catalog number Aldrich 24,671-9; CAS No. 1780-40-1) interacts with excess amine6obtaining a mixture of three compounds:91,92and93that may be divided and allocated by using HPLC or other conventional techniques. As shown, N2,N4-bis-substituted-5,6,-dichloro-2,4-pyrimidinediamine92then in the presence of halide C6 can react, for example, with the nucleophilic substance94getting connection95. In the alternative case, the connection92can be converted into N2,N4-bis-substituted-5-chloro-6-aryl-2,4-pyrimidinediamine97withthe Suzuki reaction (Suzuki). 2,4-Pyrimidinediamine95can be converted into 2,4-pyrimidinediamine99through reaction with Bn3SnH.

Experts in this field is clear, what 2,4-pyrimidinediamine according to the present invention, synthesized using the methods described above, or using other well known techniques can also be used as a starting material and/or intermediate products for the synthesis of additional compounds 2,4-pyrimidinediamine invention. A specific example shown in the following scheme (X):

Scheme (X)

In the diagram (X) R4, R5, R6L2and Racorrespond to the designations in the structural formula (I). Each Ra'independently represents Raand may be the same or different from Ra. Based on the schema (X), carboxylic acid or ester100can be converted to amide104through reaction with the amine102. In Amina 102 Ra'may be the same or different from Raacid or ester100. Similarly ether carbonate salt106can be converted to carbamate108.

The second specific example shown in the following scheme (XI):

Scheme (XI)

In scheme (XI), R4, R5, R6L2and Rccorrespond to the designations in the structural formula (I). On the basis of the scheme (XI), amide110or116can be converted to amine114or118accordingly, b is thanks to the reduction of the borane with complex metilsulfate of borane 112. Other suitable reactions for synthesizing compounds 2,4-pyrimidinediamine of the starting material 2,4-pyrimidinediamine understandable to experts in this field.

Despite the fact that many of the synthetic schemes discussed above do not reflect the use of protective groups, it is clear that in some cases the substituents R2, R4, R5, R6L1and/or L2may include functional groups that require protection. The exact properties of the used protective group will depend, among other things, on the properties of the functional group that you want to protect, and from the conditions used for the reaction in a particular synthetic scheme, which is obvious for specialists in this field. Guidance on selection of protective groups and mechanisms to attach and remove, convenient for the particular application, can be found, for example, in Greene &Wuts, above.

Prodrugs of the corresponding structural formula (II)can be prepared using a conventional modification of the methods described above. Otherwise, such prodrugs can be prepared using reactions are adequately protected 2,4-pyrimidinediamine corresponding to structural formula (I)with a suitable progroups. The conditions for such reactions and to remove the protection from the reaction product to obtain prodrugs of the corresponding FD is the mule (II), the well known.

In the literature a large number of teaching methods, mainly applicable for synthesizing as pyrimidines and starting materials described in schemes (I)to(IX). For specific guidance, the reader may consult the following sources: Brown, D. J., "The Pyrimidines", inThe Chemistry of Heterocyclic Compounds, Volume 16(Weissberger, A., Ed.), 1962, Interscience Publishers (A Division of John Wiley & Sons), New York (“Brown I”); Brown, D. J., "The Pyrimidines", inThe Chemistry of Heterocyclic Compounds, Volume 16, Supplement I(Weissberger, A. and Taylor, E. C., Ed.), 1970, Wiley-Interscience, (A Division of John Wiley & Sons), New York (Brown II); Brown, D. J., "The Pyrimidines", inThe Chemistry of Heterocyclic Compounds, Volume 16, Supplement II(Weissberger, A. and Taylor, E. C., Ed.), 1985, An Interscience Publication (John Wiley & Sons), New York (“Brown III”); Brown, D. J., "The Pyrimidines" inThe Chemistry of Heterocyclic Compounds, Volume 52(Weissberger, A. and Taylor, E. C., Ed.), 1994, John Wiley & Sons, Inc., New York, pp. 1-1509 (Brown IV”); Kenner, G. W. and Todd, A., inHeterocyclic Compounds, Volume 6, (Elderfield, R. C., Ed.), 1957, John Wiley, New York, Chapter 7 (Pyrimidines); Paquette, L. A.,Principles of Modern Heterocyclic Chemistry, 1968, W. A. Benjamin, Inc., New York, pp. 1-401 (uracil synthesis pp. 313, 315; pyrimidine synthesis pp. 313-316; amino pyrimidine synthesis pp. 315); Joule, J. A., Mills, K. and Smith, G. F.,Heterocyclic Chemistry, 3rdEdition, 1995, Chapman and Hall, London, UK, pp. 1-516; Vorbrüggen, H. and Ruh-Pohlenz, C.,Handbook of Nucleoside Synthesis, John Wiley & Sons, New York, 2001, pp. 1-631 (protection of pyrimidines by acylation pp. 90-91; silylation of pyrimidines pp. 91-93); Joule, J. A., Mills, K. and Smith, G. F.,Heterocyclic Chemistry, 4thEdition, 2000, Blackwell Science Ltd, Oxford, UK, pp. 1-589; andComprehensive Organic Synthesis, Volumes 1-9 (Trost, B. M. and Fleming, I., Ed.), 1991, Pergamon Pess, Oxford, UK.

Specialists in this field will be clear that in schemes I through XI, the N4 nitrogen may be substituted by a group R4cas noted throughout the text of the description of the present invention and in the examples.

6.4 Inhibition of signaling cascades Fc-receptor

Active compounds 2,4-pyrimidinediamine according to the present invention inhibit the signaling cascade Fc receptor, which leads, among other things, degranulation of the cells. As a concrete example of inhibition of these compounds cascades of signals FcεRI and/or FcγRI, resulting in degranulation of immune cells such as neutrophil, eosinophil cells, Metacity and/or basophilic cells. And Metacity, and basophilic cells play a Central role in disorders caused by allergens, including, for example, allergic rhinitis and asthma. Based on figure 1, under the influence of allergens, which, among other things, can be pollen or parasites, allergen-specific IgE antibodies are synthesized In a-cells that are activated by IL-4 or IL-13) and other messengers, to go to the synthesis of specific antibodies of the IgE class. These allergen-specific IgE antibodies bind to FcεRI with high affinity. After binding of the antigen associated with FcεR1 antibody IgE bound and aktiviruetsya path signal transduction receptor, IgE, which leads to degranulation of the cells and subsequent selection and/or synthesis of a variety of chemical mediators, including histamine, proteases (for example, tryptase and himizu), lipid mediators such as leukotrienes (e.g., LTC4), factors of platelet activation (PAF) and prostaglandins (e.g., PGD2), as well as a series of cytokines, including TNF-α, IL-4, IL-13, IL-5, IL-6, IL-8, GMCSF, VEGF and TGF-β. The selection and/or synthesis of these mediators from mastocytes and/or basophilic cells is a cause of early or late responses caused by allergens, and is directly connected with the processes proceeding in the forward direction, leading to a prolonged inflammatory state.

Molecular processes in the path of signal transduction receptor FcεRI, which cause the secretion of preformed mediatorsbydegranulation and selection and/or synthesis of other chemical mediators are well known and are illustrated in figure 2. Based on figure 2, FcεRI is heterotetrameric receptor, composed of IgE-binding alpha subunits, beta subunits, and two gamma subunits (gamma-glycosilated). The crosslinking of FcεRI-bound IgE by using multivalent binding substances (including, for example, IgE-specific allergen or anti-IgE antibodies, or fragments) causes rapid Association and activation of Src-dependent Lyn-kin is PS. Lyn phosphorylates the activation motifs of immunoreceptor caused by tyrosine (“ITAMS), extracellular beta - and gamma-subunits, which leads to the recruitment of additional Lyn-kinase to the beta subunit and Syk kinase to gamma-glycosilated. These related receptor kinases, which are activated by intra - and intermolecular phosphorylation, phosphorylate other path components, such as Btk-kinase, LAT and C-gamma (PLC-gamma) phospholipase. Activated PLC-gamma initiates a path that leads to activation of C-kinase protein and mobilization of Ca2+that is necessary for degranulation. Stitching FcεR1 also activates the three main classes of protein kinases, mitogen-activated (MAP),that is,ERK1/2, JNK1/2 and p38. Activation of these pathways is important in the transcriptional regulation of proinflammatory mediators, such as TNF-α and IL-6, and leukotriene CA (LTC4) lipid mediator.

Although not shown, it is believed that signaling cascade receptor FcγRI has several common elements with the signal cascade receptor FcεRI. What is essential is that like FcεRI, the receptor FcγRI includes gamma-glycosilated, which is phosphorylated and recruits Syk-kinase, as in the case of FcεRI, and activation of the signalling cascade receptor FcγRI leads, among other things, degranulation. Other Fc receptors, which are involved in gamma-glycosilated and may be subject to the active compounds 2,4-pyrimidinediamine, include, inter alia, FcαRI and FcγRIII.

The ability of the compounds 2,4-pyrimidinediamine according to the present invention to inhibit the signaling cascade Fc receptor easy to determine or confirm in thein vitroanalysis. Samples, convenient to confirm the inhibition of degranulation, FcεRI mediated described in the "Examples"section. In one typical sample of cells able to undergo the degranulation mediated FcεRI, as, for example, Metacity or basophils, first grown in the presence of IL-4, stem cell factor (SCF), IL-6 and IgE to increase expression of FcεRI exposed to test compounds 2,4-pyrimidinediamine according to the present invention and stimulated with anti-IgE antibodies (or, in the alternative case of IgE-dependent allergen). After incubation the number of chemical mediator or other chemical reagent, isolated and/or synthesized in the activation of the FcεRI signaling cascade can be determined using standard techniques and can be equated to the number of mediator or reagent isolated from control cells (that is,cells that are stimulated, but not exposed to the test compound). The concentration of test compound that causes a 50%reduction in the number of mediatorial reagent, measured relative to control cells, equal IC50the test compounds. The origin of mastocytes or basophilic cells used in the sample will depend, in particular, the preferred use of the compounds, which is obvious for specialists in this field. For example, if the connection will be used for the treatment or prevention of a particular disease, peculiar people, a convenient source of mastocytes or basophilic cells is a person or other animal that is considered to be acceptable or known clinical model for a particular disease. Thus, depending on the specific application Metacity or basophilic cells can be obtained from various animal sources from the lower mammals, such as mice and rats to dogs, sheep and other mammals, commonly used in clinical trials, and the higher mammals, such as monkeys, chimpanzees, apes, and even people. Specific examples of cells suitable for sample preparationin vitroinclude, including, basophilic cells of rodents or humans, line basophilic cell leukemia in rats, the main Metacity mice (such as bone marrow mastocyte mice “BMMC”) and primary cultured from the blood of the umbilical cord mastocyte person (“CHMC”) or other tissues, such as the Kani lungs. Methods of isolating and culturing cells of these types are well known or presented in the "Examples" section (see, for example,That Demoet al., 1999, Cytometry 36(4):340-348 and one of several applications that are simultaneously pending patent office, registration number 10/053,355, filing date - November 8, 2001, a summary of which is included in the references to this paper). Of course, the immune cells of other types, which degranulate after activation of the FcεRI signaling cascade may also be used, including, for example, eosinophils.

Experts in this field agree that quantified the mediator or the reagent is not required. The only requirement is that the mediator or agent has been isolated and/or synthesized in the initiation or activation of the signalling cascade Fc receptor. For example, based on figure 1, activation of the FcεRI signaling cascade in mastocyte and/or basophilic cells leads to numerous phenomena proceeding in the forward direction. For example, activation of the FcεRI signaling cascade immediately (i.e. within 1-3 min after activation of the receptor)withdegranulation highlighted a variety of preformed chemical mediators and reagents. Thus, in one example implementation of the invention quantified the mediator or Reagan which may be characteristic of granules ( that is,usually be present in the granules, but not in the cytoplasm of the cell). Examples granulometrically mediators or reagents that can be quantified to determine and/or confirm the activity of the compounds 2,4-pyrimidinediamine according to the present invention, include, including, granulometricheskie enzymes, such as hexosaminidase and tryptase, and granulometricheskie components, such as histamine and serotonin. Samples to quantify such factors are well known and in many cases commercially available. For example, the allocation of tryptase and/or hexosaminidase can be quantified using growing cells with cleaved substrates that fluoresce after splitting, determining the number of received fluorescence conventional methods. Such split fluorogenic substrates are commercially available. For example, fluorogenic the substrate Z-Gly-Pro-Arg-AMC (where Z=benzyloxycarbonyl and AMC=7-amino-4-methylcoumarin, produced by the company BIOMOL Research Laboratories, Inc., Plymouth Meeting, PA 19462, Catalog No. P-142) and Z-Ala-Lys-Arg-AMC (Enzyme Systems Products, a Division of ICN Biomedicals, Inc., Livermore, CA 94550, Catalog No. AMC-246) can be used to quantify the amount of allocated tryptase. Fluorogenic substrate 4-methylumbelliferyl-N-acetyl-β-D-glucosaminide (supplier: Sigma, St. Louis, MO, Catalog #69585) can be used in the IAOD to quantify the number of selected hexosaminidase. Histamine release can quantify, using commercially available enzyme-linked immunosorbent assay ELISA, as for example, ELISA analysis Immunotech histamine No. IM2015 (Beckman-Coulter, Inc.). Specific methods quantify the allocation of tryptase, hexosaminidase and histamine presented in the "Examples"section. Each of these samples may be used to determine or confirm the activity of the compounds 2,4-pyrimidinediamine according to the present invention.

As shown again in figure 1, degranulation represents only one of several reactions induced signaling cascade FcεRI. In addition, activation of this signaling pathway leads tode novothe synthesis and secretion of cytokines and chemokines, such as IL-4, IL-5, IL-6, TNF-α, IL-13 and MIP1-α, and release of lipid mediators such as leukotrienes (e.g., LTC4), factors of platelet activation (PAF) and prostaglandins. Therefore, the compounds 2,4-pyrimidinediamine according to the present invention can also be assessed in relation to their activity with the help quantify the amount of one or more of these selected mediators and/or synthesized using activated cells.

In contrast to the above discussed granulometrically components of these mediators "late phase" not allocated immediately after activation of the FcεRI signaling cascade. T is thus, when quantifizierung these mediators later stage should take measures to ensure that the culture of activated cells grown in a period of time sufficient to allow synthesis (if necessary) and allocation quantifizierung mediator. Usually PAF and lipid mediators, such as leukotriene C4, highlighted through 3-30 min after activation of the FcεRI. Cytokines and other mediators of the late phase are allocated approximately 4-8 hours after activation of the FcεRI. Times of cultivation, specific mediators known to specialists in this field. Specific guidance and samples presented in the "Examples"section.

The specific number of the selected mediator of the late phase it is possible to quantify, using any standard methods. In one example implementation of the present invention is the amount (quantity) you can quantify, using ELISA. The set of samples ELISA, convenient to quantify selected TNFα, IL-4, IL-5, IL-6 and/or IL-13 can be obtained, for example, the company Biosource International, Inc. Camarillo, CA 93012 (see, for example, catalog number No. KHC3011, KHC0042, KHC0052, KHC0061 and KHC0132). The set of samples ELISA, convenient to quantify isolated from cells leukotriene C4 (LTC4), can be purchased in the company Cayman Chemical Co., Ann Arbor, MI 48108 (see, for example, the catalog number No. 520211).

As a rule, the compounds of the active 2,4-pyrim is gentilino according to the present invention will have a concentration IC 50in relation to the degranulation mediated receptor FcεRI and/or level selection or synthesis of the mediator about 20 μm or less, in accordance with the measurement resultsin vitrosuch as one ofin vitrosamples discussed above or in the "Examples"section. Of course, specialists in this field it is clear that compounds that exhibit low values of IC50for example, about 10 μm, 1 μm, 100 nm, 10 nm, 1 nm or even lower, are particularly useful.

Specialists in this field will agree with the fact that different mediators discussed above, can cause different negative effects or different levels of the same negative impacts. For example, the lipid mediator LTC4 is a strong vasoconstrictor tool: his selenocystine in terms of narrowing of the blood vessels is approximately 1000 times greater than selenocystine histamine. As another example, in addition to mediating atopic reactions or hypersensitivity reactions type I that can result in cytokines, which are also capable of causing the transformation of tissues and cell proliferation. Thus, despite the use of compounds which inhibit the secretion and/or synthesis of one of the previously reviewed by chemical mediators, experts in this field soglasate is, that compounds that inhibit the secretion and/or synthesis of most, or even all of the above mediators, undoubtedly, will find wider application because of their ability to improve or completely suppress the majority or even all of the adverse effects caused by the individual mediators. For example, compounds that inhibit the secretion of mediators of all three types - granulometrically mediators, lipid and cytokine - effective in the treatment or prevention of hypersensitivity reactions immediate type I and related chronic symptoms.

Compounds according to the present invention, is able to inhibit the selection of a mediator more than one type (for example,granulometricheskogo mediator or mediator of the late phase), can be identified using the definitions of the indicator IC50regarding exemplary mediator each class, using a variety ofin vitrosamples discussed above (or other equivalentin vitrosamples). Compounds according to the present invention, which can suppress the mediators more than one type, will usually show the values of the IC50less than 20 microns mediators each of the tested type. For example, the connection with the value of the IC501 μm with respect to the allocation of histamine (IC50Geest is min and with the value of the IC501 nm relative to the synthesis of leukotriene LTC4 and/or selection

(IC50LTC4) is characterized as immediate release mediators (inherent in the granules), and the release of mediators of the late phase. As another specific example, the connection with the values IC50tryptase10 ám IC50LTC4- 1 μm and IC50IL-4- 1 μm, which inhibits instant selection of mediators (characteristic granules), as well as the secretion of lipid and cytokines mediators. Although in the above specific examples are used IC50one mediator - a representative from each class, the experts in this field would agree that the value of the IC50most or even all of mediators, comprising one or more classes can also be obtained. For specialists in this field will be obvious quantity (amount) and type (species) of mediators, for which data on the IC50must be set when the specific connection and application.

Such samples can be used to test the inhibition of the cascades transduction of signals initiated by other signal Fc receptors, such as FcαRI, FcγRI and/or FcγRIII with the usual modification. For example, the ability of compounds to inhibit the Tr is Nuccio signal FcγRI can be checked using samples similar to the one described above, except that FcγRI signaling cascade is activated, for example, by growing cells with IgG and allergen-specific IgG or antibody instead of IgE and allergen-specific IgE or antibodies. Specialists in this area known suitable types of cells, activating reagents and reagents to quantify required to test the inhibition of other Fc receptors, such as Fc receptors, members of the gamma-glycosilated.

One of the most useful class of compounds includes compounds of 2,4-pyrimidinediamine, which inhibit the secretion of mediators of granules type of immediate and late phase mediators with roughly equivalent values IC50. "Roughly equivalent" means that the values of the IC50for each mediator type differ from each other not more than 10 times. Another particularly useful class of compounds includes compounds of 2,4-pyrimidinediamine, which inhibit the secretion of mediators of granules immediate type and mediators of cytokine with roughly equivalent values IC50. In specific examples of implementation of the present invention such compounds inhibit the secretion of the following mediators with roughly equivalent values IC50: histamine, tryptase, hexosaminidase, IL-4, IL-5, IL-6, IL-13, TNFα and LTC4. Such connected what I particularly effective in addition, improvement or complete elimination of both early and late responses associated with atopic or reactions of immediate type hypersensitivity I.

Ideally, the ability to inhibit the secretion of mediators of all desirable types would be characterized by a single connection. However, there may be identified a mixture of compounds that provide the same result. For example, the first compound that inhibits the release granulometrically mediators can be used in combination with a second compound that inhibits the release and/or synthesis of mediators of cytokine.

In addition to the ways degranulation FcεRI or FcγRI discussed above, the degranulation of mastocytes and/or basophilic cells may be caused by other reagents. For example, ionomycin, representing ionophor calcium, which bypasses the mechanism of transduction of early signals FcεRI or FcγRI cells, directly causes the flow of calcium, which triggers degranulation. As follows from figure 2, activated PLCγ initiate pathways leading to, inter alia, the mobilization of calcium ions and subsequent degranulation. As shown in this figure, such a mobilization of Ca2+invoked at a later stage of the path of FcεRI signal transduction. As noted above and shown in figure 3, ionomycin directly calls mobiles is the situation of Ca 2+and the flow of Ca2+that leads to degranulation. Other ionophores that cause degranulation in this way include A23187. The ability of ionophores such as ionomycin, to cause degranulation to bypass the early stages of signaling cascades FcεRI and/or FcγRI, you can use them as screen counter to identify the active compounds according to the present invention, which particularly affect their activity in degranulation and the inhibition by blocking or suppressing early signaling cascades FcεRI or FcγRI, as discussed above. Compounds that specifically inhibit this early degranulation mediated FcεRI or FcγRI receptors, inhibit not only the degranulation and subsequent rapid release of histamine, tryptase, and other components containing granules, but also ways of activation prosopalgia, causing allocation of TNFα, IL-4, IL-13 and lipid mediators such as LTC4. Thus, compounds that specifically inhibit this early degranulation mediated FcεRI or FcγRI receptors, block or inhibit not only acute atopic reactions or hypersensitivity reactions type I, but also and late responses involving multiple mediators of inflammation.

Compounds according to the present invention that fully inhibit early Tehran is the transmission, indirect FcεRI and/or FcγRI-receptors are compounds that inhibit the degranulation mediated FcεRI and/or FcγRI receptors (having, for example,,the values of the IC50less than 20 μm with respect to the allocation granulometricheskogo mediator or component measurementsin vitroin the sample with cells that are stimulated binding reagent IgE or IgG), but not significantly inhibit the degranulation caused by ionophores. In one example implementation of the present invention compounds are considered as slightly inhibiting the degranulation caused by iodoform, if determined in vitro the value of the IC50degranulation caused by iodoform, does not exceed 20 μm. Of course, the active compounds that show even higher values IC50due iodoform degranulation or not suppress due inforom the degranulation, is particularly effective. In another example implementation of the present invention compounds are considered to be negligible any abscopal the degranulation caused by iodoform if they show more than a 10-fold difference values IC50degranulation mediated FcεRI and/or FcγRI and due iodoform degranulation, measuredin vitroin a sample. Samples suitable for determining the value of the IC50obuslovlen the th iodoform degranulation, include any of the previously discussed samples of degranulation, provided that the cells are stimulated or activated by iodoform calcium, such as ionomycin or A (A.G. Scientific, San Diego, CA), causing degranulation, instead of anti-IgE antibodies or allergen-specific IgE. Specific tests to assess the ability of a compound 2,4-pyrimidinediamine according to the present invention to inhibit caused by ionophores the degranulation presented in the "Examples"section.

Specialists in this field will be clear that compounds that exhibit a high degree of selectivity to the degranulation mediated FcεRI, find concrete application, since such compounds selectively affect the cascade of FcεRI and do not affect other mechanisms of degranulation. Similarly, compounds which exhibit a high degree of selectivity with respect to the degranulation mediated FcγRI receptors, find concrete application, since such compounds selectively affect the cascade of FcγRI and do not affect other mechanisms of degranulation. Compounds that exhibit a high degree of selectivity, generally 10 or more times more selective towards FcεRI mediated or FcγRI receptors degranulation than to degranulation caused by ionophores as, for example, degradation is ulacia, due to ionomycin.

Accordingly, the activity of the compounds 2,4-pyrimidinediamine according to the present invention can also be confirmed using biochemical or cellular samples the activity of Syk kinase. As shown in figure 2, in FcεRI signaling cascade in mastocyte and/or basophilic cells Syk-kinase phosphorylates LAT and PLC-gamma, which leads, among other things, degranulation. Any of these activities can be used to confirm the activity of the compounds 2,4-pyrimidinediamine according to the present invention. In one example implementation of the present invention this activity is confirmed by connecting a dedicated Syk-kinase or its active fragment of the compound 2,4-pyrimidinediamine in the presence of the substrate of Syk-kinase (for example,synthetic peptide or protein, if you know that it must be phosphorylated using Syk in the signaling cascade) assessment of phosphorylation of the substrate of Syk kinase. Alternatively the sample may be prepared using cells that Express Syk-kinase. Cells can Express Syk-kinase endogenous (internally) or they can be built to Express the recombinant Syk-kinase. Cells can also Express the neural substrate of Syk kinase. Cells suitable for preparation of such to the control samples, as well as methods of creating suitable cells, obvious to a person skilled in this field. Specific examples of biochemical or cellular samples, convenient to confirm the activity of the compounds 2,4-pyrimidinediamine presented in the "Examples"section.

In General, inhibitors of Syk kinase will have values IC50in relation to the activity of Syk kinase as, for example, the ability of Syk-kinase to fosforilirovanii synthetic or endogenous substratein vitroor cell sample, about 20 μm or less. Specialists in this field would agree that the compounds with smaller values IC50of , for example, 10 μm, 1 μm, 100 nm, 10 nm, 1 nm or even lower, are particularly effective.

6.5 applications and formulations

As noted earlier, the active compounds according to the present invention inhibit the signaling cascade Fc receptor and, in particular, Fc receptors, including gamma-glycosilated, such as signaling cascades FcεRI and/or FcγRI, which are, inter alia, to the selection and/or synthesis of chemical mediators from cellsbydegranulation or other processes. Also discussed that the active compounds are effective inhibitors of Syk kinase. Therefore, the active compounds according to the present invention can be used in differentin vitro, in vivoandex vivothe conditions of the La regulation or inhibition of Syk-kinase, signaling cascades, in which Syk-kinase plays a role in signal cascades of Fc receptors and biological reactions caused by such signaling cascades. For example, in one example implementation of the present invention compounds can be used to inhibit Syk kinasein vitroorin vivoactually in any cell type expressing Syk-kinase. They can also be used for regulatory cascades of signal transduction in which Syk-kinase plays a role. Such Syk-dependent cascades of signal transduction include, including, cascades of signal transduction FcεRI, FcγRI, FcγRIII, BCR and integrin. Connection you can also usein vitroorin vivofor regulation and, in particular, suppression of cellular or biological reactions caused by such Syk-dependent cascades of signal transduction. Such cellular or biological responses include, including, respiratory bursts, cellular adhesion, cellular degranulation, raspletanie cells, migration of cells, aggregation of cells, phagocytosis, synthesis and secretion of the cytokine, maturation cells and the flow of ions Ca2+. It is essential that these compounds could be used for the inhibition of Syk-kinasein vivoas a therapeutic approach towards the treatment or prevention of disease, or is completely or partially mediated by Syk activity-Ki is the basics. Some examples of diseases mediated Syk kinase, which can be treated or prevented by such compounds is described in more detail below.

In another example implementation of the present invention the active compounds can be used for regulation or inhibition of signaling cascades Fc receptor and/or FcεRI and/or FcγRI-mediated degranulation as a therapeutic approach towards the treatment or prevention of diseases characterized by, caused by and/or associated with the release or synthesis of chemical mediators such signaling cascades, or degranulation of Fc receptors. Such treatment can be assigned to animals in the veterinary conditions or people. As an example, diseases that are characterized by, caused or associated with such selection, synthesis or degranulation of mediator and, therefore, amenable to treatment or prevention with active compounds include, but are not limited to, the following: genetic predisposition to allergic diseases, anaphylactic hypersensitivity or allergic reactions, allergies (e.g., allergic conjunctivitis, allergic rhinitis, atopic asthma, atopic dermatitis and food Allergy), low grade scarring (i.e. scleroderma, increased fibrosis, the formation of keloids, poliopterus the district scars, pulmonary fibrosis, vasospasm, migraine, reperfusion injury and posleinfarktnoy period), diseases associated with tissue destruction (for example,chronic obstructive pulmonary disease (COPD), kariobangi and posleinfarktnoy period), diseases associated with inflammation of the tissues (for example,, irritable bowel syndrome, spastic colon and inflammatory bowel disease), inflammation and scarring.

In addition to a huge number of the above-mentioned diseases resulting cell analysis and animal testing data confirm that the compounds 2,4-pyrimidinediamine described in this invention are also useful in the treatment or prevention of autoimmune diseases, as well as various symptoms associated with such diseases. Types of autoimmune diseases, treatment or prevention of which is possible by using compounds 2,4-pyrimidinediamine, in total, include disorders associated with the tissue damage that result from humoral and/or mediated cell response immunogen or antigens of endogenous and/or exogenous nature. Such diseases are often characterized as diseases associated with penatrations hypersensitivity reactions (for example, II, III and/or type IV).

According to the discussion is the group of above, hypersensitivity reactions type I mainly arise from the allocation of pharmacologically active substances, such as histamine, mastocytoma and/or basophils as a result of contact with a specific exogenous antigen. As noted above, these reactions type I play a role in many diseases, which include allergic asthma, allergic rhinitis, etc.

Hypersensitivity reactions type II (also known as cytotoxic, cytolytic caused by complement or stimulated cell hypersensitivity reactions) occur when the reaction of antibodies with antigenic components of cells or tissues with either antigen or hapten, which are inextricably linked with the cells or tissues. Diseases that are typically associated with hypersensitivity reactions type II include, but are not limited to, the following: autoimmune hemolytic anemia, congenital anemia of the newborn and the syndrome?.

Hypersensitivity reactions type III (also known as hypersensitivity reactions caused by toxic, soluble, or immune complexes) arise from deposits in blood vessels or tissues soluble circulating antigen-immunoglobulin complexes, which is accompanied by an acute inflammatory reactions in the natural immune complex deposits. Unlimited examples of the prototypical diseases resulting from reactions type III include reaction artusa, rheumatoid arthritis, serum sickness, systemic erythematous lupus, certain kinds of glomerulonephritis, multiple sclerosis and bullous pemphigoid.

Hypersensitivity reactions type IV (often referred to as a cell, cell-mediated, delayed, or tuberculin hypersensitivity reactions) are caused by sensitized T-lymphocytes, which are formed by contact with a specific antigen. Unlimited examples of diseases that involve reactions type IV, include contact dermatitis and allograft rejection.

Autoimmune diseases that are associated with any of the above penatrations hypersensitivity reactions may be treated or prevented using the compounds 2,4-pyrimidinediamine according to the present invention. In particular, these methods can be used for treatment or prevention of autoimmune diseases, often characterized as an autoimmune disorder, single organ or single cell type, which include, but are not limited to, the following: Hashimoto thyroiditis, autoimmune hemolytic anemia, autoimmune atrophic gastritis of pernicious anemia, autoimmune the first encephalomyelitis, autoimmune orchitis syndrome?, autoimmune thrombocytopenia, metastatic ophthalmia, bulbospinal paralysis, graves ' disease, primary biliary cirrhosis, chronic aggressive hepatitis, ulcerative colitis and membranous glomerulopathy, as well as autoimmune disease, often characterized by the presence of systemic autoimmune disorders, which include, but are not limited to, the following: systemic lupus erythematous, rheumatoid arthritis, Sjogren syndrome, Reiter syndrome, polymyositis-dermatomyositis, systemic sclerosis, Nowotny polyarteritis, multiple sclerosis and bullous pemphigoid.

Specialists in this field would agree that many of these autoimmune diseases associated with severe symptoms, weakening symptoms which represents a significant advance in the treatment, even in cases when you are unable to improve the condition of the underlying disease. Many of these symptoms and the stage of the underlying disease, are the result of activating FcγR signaling cascade in monocytes. Because the connections 2,4-pyrimidinediamine according to the present invention are potent inhibitors such FcγR signaling pathways in monocytes and other cells, the described methods can be used in the treatment and/or prevention of many unwanted SIM the volume, related to the above-mentioned autoimmune diseases.

As an example, rheumatoid arthritis (RA) usually causes swelling, pain, loss of mobility and increased sensitivity damaged joints in the whole body. For RA is characterized by chronically inflamed synovial membrane, densely populated by lymphocytes. Membrane synovial membrane, which typically has a thickness in a single cell layer becomes saturated cells and takes the form similar to lymphoid tissues, including dendritic cells, T-, b - and NK-cells, macrophages and clusters of plasmacytes. This process, combined with the abundance of immunopathologic mechanisms, which include the formation of antigen-immunoglobulin complexes, ultimately leads to disruption of the integrity of the joints that leads to deformation, the permanent loss of functioning and/or erosion of the bone of the joint or in the immediate vicinity of the joint. The described methods can be used to treat or relieve the state of any individual, several or all of the symptoms of RA. Thus, within the context of the RA methods of treatment (described in more General terms,below), which help to reduce symptoms or improve symptoms often associated with RA, regardless of concomitant treatment success basically the disease (RA) and/or reducing the number of circulating rheumatoid factor ("RF").

As another specific example, systemic lupus erythematous ("SLE"), which is often associated with symptoms such as fever, pain in the joints (arthralgia), arthritis and Ceresit (pleuritis or pericarditis). Within the context of SLE methods of treatment, which help to reduce symptoms or improve symptoms often associated with SLE, regardless of concomitant success in the treatment of the underlying disease (SLE).

As another specific example, multiple sclerosis (MS), the damage from which includes impaired visual acuity of the patient; the development of double vision; impaired mobility, which affects the ability to walk and act hands; incontinence stomach and bladder; spasticity; and limited sensitivity to touch, pain and temperature). Within the context of the MS methods of treatment to improve the condition or delay in the development of any specific or several damaging factors, often associated with MS, regardless of the concomitant success in the treatment of major diseases (MS).

When used for treatment or prevention of diseases such active compounds may be assigned individually, as mixtures of one or more active compounds or in the form of a mixture and the and combination with other substances, effective in the treatment of such disorders and/or symptoms associated with such diseases. These active compounds are also administered in mixture or combination of substances, which are used to treat other disorders or diseases, such as steroids, membrane stabilizers, 5LO inhibitors, inhibitors of the synthesis and receptor leukotriene inhibitors of isotype switching to IgE or IgE synthesis, inclusion isotype IgG or IgG synthesis, β-agonists, tryptase inhibitors, aspirin, COX inhibitors, methotrexate, anti-TNF drugs, Rituxan, PD4 inhibitors, p38 inhibitors, PDE4 inhibitors, antihistamines, etc. These active compounds can be assignedper se(independently) in the form of prodrugs or as pharmaceutical preparations containing the active compound or prodrug.

Medicinal preparations containing active compounds according to the present invention (or their prodrugs), can be produced using a conventional mixing, dissolving, granulating, dragobrath otmuchivanie, emulsification, encapsulation, processes of entrainment, or lyophilization. These compounds may be prepared in the usual way, using one or more physiologically acceptable carriers, diluents, excipients or auxiliaries that facilitate processing of the active compounds in medicine that can be used for pharmaceutical purposes.

The active compound or the prodrug can be prepared as pharmaceutical compositionsper seor in the form of a hydrate, MES, N-oxide or pharmaceutically acceptable salt, as described above. Typically, such salts are more soluble in aqueous solutions than the corresponding free acids and bases, while you can get salt less soluble than the corresponding free acids and bases.

The pharmaceutical compositions according to the present invention may take the form convenient for almost any application, including, for example, external, eye, internal, transbukkalno, systemic, nasal, injection, transdermal, rectal, vaginal, etc. or shape suitable for the purpose in the form of inhalation or insufflation.

For external use active connection (connection) or prodrug (prodrugs) may be prepared in the form of solutions, gels, ointments, creams, suspensions, etc. that are well known in the literature.

Compositions for systemic injections include those that are intended for use in injection form,for example,subcutaneous, intravenous, intramuscular, intrathecal or intraperitoneal injection, as well as those designed for transdermal, through the mucous membrane, internal or pulmonary administration.

Eff is active injectable preparations include sterile suspensions, solutions or emulsions of the active compounds (compounds) in aqueous or oily solvents. The compositions can also include forming substances, such as suspendisse agent, a stabilizing agent and/or dispersing agent. Finished dosage forms for injection can be presented in the form of individual doses, for example in ampoules or in containers with multidose, and may contain added preservatives.

In an alternative embodiment, the injectable composition may be administered in powder form, in which to restore the original consistency before use added convenient solvent, including, but not limited to, sterile, not sotiriadou pyrogen water, buffer, dextrose, etc. To this end the active connection (connection) can be dried using any known techniques such as lyophilization, and before use, to return to its original form.

To apply through the mucous membrane in the composition used wetting agents, corresponding to the existing biological barrier. Such compounds are known in the literature.

For oral administration the pharmaceutical compositions may take the form of, for example, pellets (tablets), tablets or capsules prepared by conventional means with pharmaceutically acceptable use of fillers, such as the connection is the following substances (for example, pre gelatinization corn starch, polyvinylpyrrolidone or hypromellose); fillers (e.g. lactose, microcrystalline cellulose or calcium phosphate); lubricants (e.g. magnesium stearate, talc or silica); dezintegriruetsja substances (e.g., potato starch or starch glycolate sodium); or wetting agents (e.g. sodium lauryl sulphate). Tablets can be coated using well known methods such substances, such as sugar, film or enteric-soluble coating.

Liquid preparations for internal use can be in the form of, for example, elixirs, solutions, syrups or suspensions, or may be supplied as a dry product before use, dissolve in water or another appropriate solvent. Such liquid preparations can be prepared by ordinary methods using pharmaceutically acceptable additives such as suspendresume agents (e.g. sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g. lecithin or gum); anhydrous solvents (for example, almond oil, oily esters, ethyl alcohol, cremophor™ or fractionated vegetable oils); and preservatives (e.g. methyl or propyl-p-hydroxybenzoate or COP the new acid). If necessary, the preparations may also contain buffer salts, preservatives, flavoring, coloring and sweetening agents.

As is well known, the preparations for internal use can be conveniently prepared to obtain a controlled release of the active compound or prodrug.

For transbukkalno application of the compositions can take the form of tablets or lozenges made in the traditional way.

For rectal or vaginal application of the active compound (compounds) can be prepared as solutions (for retention enemas)suppositories (candles) or ointments containing suppozitornyj base, such as cocoa butter or other glycerides.

For intranasal or application via inhalation or insufflation active connection (connection) or prodrug (prodrugs) may conveniently be supplied in the form of aerosol spray cans of overpressure or spray with easy-to-use compressed fluid, for example DICHLORODIFLUOROMETHANE, trichloromethane, dichlorotetrafluoroethane, fluorocarbons, carbon dioxide or other suitable gas. In the case of aerosols under pressure dosage can be determined by using the valve for the issuance of measuring the amount of the drug. Capsules and cartridges, IP is alzhemier in inhaler or apparatus for injection (for example, capsules and cartridges consisting of gelatin) can be prepared so as to contain a powder mix of medicinal compounds and convenient powder form, such as lactose or starch.

A specific example of a composition in the form of aqueous suspensions, convenient for intranasal using commercially available intranasal aerosol device, includes the following ingredients: the active compound or prodrug (0.5 to 20 mg/ml); benzylaniline (0.1-0.2 mg/ml); Polysorbate 80 (ether polyoxyethylene fatty acids) (TWEEN® 80; 0.5 to 5 mg/ml); carboxymethylcellulose sodium or microcrystalline cellulose (1-15 mg/ml); phenylethanol (1-4 mg/ml) and dextrose (20-50 mg/ml). the pH of the final suspension can be adjusted in the range from about pH 5 to pH 7 with a typical pH of 5.5.

Another specific example of an aqueous suspension suitable for administration of compounds through inhalation, and, in particular, for the introduction of compounds of the present invention, contains 1-20 mg/ml of the compound or prodrug, 0.1 to 1% (vol./about.) Polysorbate 80 (TWEEN®80), 50 mm citrate and/or 0.9% sodium chloride.

For ophthalmic use active connection (connection) or prodrug (prodrugs) may be prepared in the form of a solution, emulsion, suspension, etc. suitable for ophthalmic use. In the literature there are many solvents, convenient for test and the use of compounds used as eye means. Specific non-limiting examples are described in U.S. patents№№ 6261547; 6197934; 6056950; 5800807; 5776445; 5698219; 5521222; 5403841; 5077033; 4882150 and 4738851.

For prolonged delivery of the active connection (connection) or prodrug (prodrugs) may be prepared in the form of delayed drug absorption, taken by implantation or intramuscular injection. The active ingredient can be prepared using suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil)or ion exchange resins, or sparingly soluble derivatives, for example, a sparingly soluble salt. Alternatively can be used produce a transdermal delivery system, such as an adhesive disc or sticker, which slowly release the active connection (connection) for subcutaneous absorption. This purpose can be used stimulants penetration to improve subcutaneous absorption of active compounds (compounds). Convenient transdermal patches are described, for example, in U.S. patents№№ 5407713; 5352456; 5332213; 5336168; 5290561; 5254346; 5164189; 5163899; 5088977; 5087240; 5008110 and 4921475.

Alternatively can be used by other systems of delivery of the drug. Liposomes and emulsions are well known examples of the solvent is th vector, which can be used for delivery of active compounds (compounds) or prodrug (prodrugs). Can also be used in certain organic solvents, such as dimethylsulfoxide (DMSO), although this usually leads to higher toxicity.

Pharmaceutical compositions optionally can be present in the form of packaging or dispensing device, which may contain one or more dosage forms, the active compound (compounds). In this package may be, for example, metal or plastic foil, such as a blister pack. The pack or dispenser may be accompanied by instructions for use.

6.6 Effective dosage

Active connection (connection) or prodrug (prodrugs) according to the present invention or their compositions will generally be used in amounts effective to achieve the intended results, for example in amounts effective for the treatment or prevention of specific diseases. Connection (connection) may be administered therapeutically to achieve therapeutic result or prophylactically to achieve prophylactic result. Under therapeutic result means the elimination or reduction of the primary disorder, regarding to the showing treatment is conducted, and/or the elimination or weakening of one or more symptoms associated with the primary disorder to such an extent that the patient felt improvement in health or condition, even if he continues to suffer with this disorder. For example, the appointment of active compounds to a patient suffering from allergies, provides a therapeutic result not only when the main allergic reaction eliminated or weakened, but also when the patient experiences a weakening of the severity or duration of symptoms of allergies due to exposure to the allergen. As another example, a therapeutic result in the case of asthma includes breathing improved after an asthmatic attack or reducing the frequency or severity of asthmatic episodes. Therapeutic result also includes suspension or delay of disease development, regardless of whether it was an improvement.

For prophylactic use, the connection can be prescribed to a patient at risk of developing one of the previously described diseases. For example, if it is unknown whether the patient is prone to allergic reactions to a particular drug, the connection can be assigned to drug administration to avoid or reduce an allergic reaction to this medication. Alternatively prophylactic purpose monoplanet, to avoid the patient's symptoms associated with the primary disorder. For example, the connection may be assigned suffering from allergies prior to expected exposure to the allergen. The connection can also be prophylactically assigned to healthy people who are repeatedly exposed to the agents associated with one of the above diseases, in order to avoid disorder. For example, the connection may be assigned a healthy person is repeatedly exposed to an allergen, is known for its ability to cause allergies, such as latex, with the intention of preventing the development of allergies in this man. Alternatively the connection can be assigned to a patient suffering from asthma, to activities which causes asthma attacks, to reduce their severity or completely avoid symptoms of asthma episodes.

The number assigned to the connection depends on many factors, including, for example, specific indicators, method of application, whether the treatment is prophylactic or therapeutic, the severity of the illness, and the age and weight of the patient, the bioaccumulation of specific active compounds, etc. the Accuracy of determination of the effective dose with ease is determined by a specialist.

Effective the dose can be estimated initially using samples in vitro. For example, initial dose in animals can be formulated so that the concentration of circulating in the blood or serum of the active compounds was similar to or exceeded the value of the IC50connection-specific in accordance with the measurement results of the samplein vitroas, for example,in vitroCHMC or BMMC, as well as in other samplesin vitrodescribed in the "Examples"section. The accuracy of calculating dosages to achieve such circulating blood or serum concentrations taking into account the potential of a particular connection is easily determined by a skilled physician. For more information the reader is referred to the source: Fingl &Woodbury, “General Principles,”In: Goodman and Gilman''s The Pharmaceutical Basis of Therapeutics, Chapter 1, pp. 1-46, latest edition, Pagamonon Press, and the references given in this book.

The initial dose can be assessed according to thein vivoanalysis using, for example, animal models. Animal models used to test the validity of the compounds to treat or prevent the above diseases are well known in the literature. Useful animal models for the study of hypersensitivity or allergic reactions are described in the sources: Foster, 1995, Allergy 50 (21 Suppl): 6-9, discussion 34-38 and Tumaset al., 2001, J. Allergy Clin. Immunol. 1076):1025-1033. Useful animal models for the study of allergic rhinitis described in the sources: Szelenyiet al., 2000, Arzneimittelforschung 50(11):1037-42); Kawaguchiet al., 1994, Clin. Exp. Allergy 24(3):238-244) and Sugimotoet al., 2000, Immunopharmacology 48(1):1-7. Useful animal models for the study of allergic conjunctivitis are described in the sources: Carreraset al., 1993, Br. J. Ophthalmol. 77(8):509-514; Saigaet al., 1992, Ophthalmic Res. 24(1):45-50; and Kunertet al., 2001, Invest. Ophthalmol. Vis. Sci. 42(11):2483-2489. Useful animal models for the study of the system mastocytosis described in the sources: O'keefeet al., 1987, J. Vet. Intern. Med. 1(2):75-80 and Bean-Knudsenet al., 1989, Vet. Pathol. 26(1):90-92. Useful animal models for the study of Hyper-IgE syndrome is described in the source: Clamanet al., 1990, Clin. Immunol. Immunopathol. 56(1):46-53. Useful animal models for the study of B-cell lymphoma is described in the sources: Houghet al., 1998, Proc. Natl. Acad. Sci. USA 95:13853-13858 and Hakimet al., 1996, J. Immunol. 157(12):5503-5511. Useful animal models for the study of atopic disorders such as atopic dermatitis, atopic eczema and atopic asthma, described in the sources: Chanet al., 2001, J. Invest. Dermatol. 117(4):977-983 and Sutoet al., 1999, Int. Arch. Allergy Immunol. 120(Suppl 1):70-75. Specialists with an ordinary level of skill can easily use this information to determine what Osinovka, suitable for assignment to a person. Additional useful animal models described in the "Examples"section.

The size of the dose can usually be in the range of from about 0.0001, or 0.001 or 0.01 mg/kg/day to about 100 mg/kg/day, but they can be larger or smaller depending, among other factors, the activity of the substance, its potential, method of appointment and the various factors described above. The size of the dose and reception intervals can be adjusted individually to provide levels of connectivity (connections) in the plasma is sufficient to maintain therapeutic or prophylactic effect. For example, the compounds can be assigned to receive once a week, several times a week (e.g. every other day), it every day or several times a day depending, among other things, on the method of application, with specific indications treatment and solution prescribing physician. In cases of local injection or selective admission, as, for example, an external application, the effective local concentration of the active compounds (compounds) may not be related to plasma concentration. Specialists in this field will be able to optimize effective local dosages without experimental verification.

Preferably, the connection (connection) provided therapeutics is s or prophylactic effect, without causing substantial toxicity. The toxicity of the compounds (compounds) can be determined using standard pharmaceutical procedures. The ratio between toxic and therapeutic (or prophylactic) effects of dose represents a therapeutic index drugs. Preference should be given to the connection (connection) with a high therapeutic index.

In addition to the description of the invention below, the following examples illustrating its action, but does not limit its application.

EXAMPLES

7.1 Connection of 2,4-pyrimidinediamine

A large number of N4-substituted-N2-monosubstituted-4-pyrimidinediamine was prepared using the methods described in this text. These compounds are shown in table 1.

7.2 Connection of 2,4-pyrimidinediamine according to the present invention inhibit the degranulation mediated by receptors FcεRI

The ability of the compounds 2,4-pyrimidinediamine according to the present invention to inhibit IgE-induced degranulation was demonstrated on the example of different cellular assays on cultured mastocyte person (CHMC) and/or cells obtained from the bone marrow of the mouse (BMMC). Inhibition of degranulation was measured under the low and high density cell population using quantitative the analysis selection granulometrically factors: tryptase, histamine and hexosaminidase. Inhibition of separation and/or synthesis of lipid mediators was assessed by measuring the allocation of leukotriene LTC4, and inhibition of separation and/or synthesis of cytokines was observed by quantitative analysis of TNF-α, IL-6 and IL-13; quantitative analysis of tryptase and hexosaminidase was carried out using fluorogenic substrates in accordance with the description given in the specific examples. Quantitative analysis of histamine, TNFα, IL-6, IL-13 and LTC4 was performed using the following commercial kits ELISA: histamine (provider Immunotech", catalogue No. 2015, Beckman Coulter), TNFα (supplier "Biosource", catalogue No. KHC3011), IL-6 (supplier "Biosource", catalogue No. KMC0061), IL-13 (supplier "Biosource", catalogue No. KHC0132) and LTC4 (provider Cayman Chemical, catalog No. 520211). Protocols for conducting various analyses are described below.

7.2.1 Cultivation mastocytes and basophils man

Mastocyte and human basophils cultured from CD34-negative progenitor cells in accordance with the following description (see also the methods described in the simultaneously filed patent application U.S. serial No. 10/053355, filing date November 8, 2001, described in this document by reference).

7.2.1.1 preparation of the complete nutrient medium STEMPRO-34

For the preparation of a complete nutrient medium (CM) STEMPR-34, 250 ml STEMPRO-34™ serum-free medium (SFM) (supplier: GibcoBRL, catalog No. 10640) was placed in a flask filtration. In the same flask was added 13 ml of a nutritional Supplement (NS) "STEMPRO-34 Nutrient Supplement" (supplier: GibcoBRL, catalog No. 10641) (the preparation process described in more detail below). Vessel under nutrient supplements were washed about 10 ml of serum-free medium (SFM) was added into the flask for filtering. After adding 5 ml L-glutamine (200 mm; supplier: Mediatech, catalogue number MT 25-005-CI) and 5 ml 100X penicillin/streptomycin (pen-strap”; supplier HyClone, catalog No. SV30010), the volume was brought to 500 ml by adding serum-free medium (SFM) and filtered the solution.

The greatest number of variables in the preparation of complete culture medium (CM) provides a method by which thawed and mixed nutrient Supplement (NS) before the introduction in serum-free medium (SFM). Defrost nutritional supplements (NS) must be made on a water bath at 37°C with a circular mixing without swirl or shake until dissolved. When mixing it is necessary to monitor whether there was nerastvorim lipids. If any, and the solution is not homogeneous, it is necessary again to put the additive in a water bath and continue the mixing process to obtain odnorodnoj the solution. Sometimes this component is dissolved immediately, sometimes after one or two cycles of mixing, and sometimes not dissolved. If after one or two hours a nutritional Supplement does not come in the form of a homogeneous solution, it should be rejected and unfreeze new. Do not use nutritional Supplement NS, which has a heterogeneous appearance after thawing.

7.2.1.2 the Increased population of CD34+cell

Initial and quite a small population of CD34-positive (or CD34+) cells (1-5 × l06cells) was increased to a relatively high population of CD34-negative progenitor cells (about 2-4 × l09cells) with the use of the nutrient medium and the methodology described below. CD34+ cells from a single donor) were supplied by "Allcells" (Berkeley, CA). Because of a certain degree of variation from the point of view of quality and quantity of CD34+ cells, usually supplied by the company, the obtained cell cultures were placed in a conical tube with a capacity of 15 ml and made up to volume of 10 ml in complete culture medium before use.

At day 0 was counted viable (refractile) cells, which are then placed in a centrifuge and spun at a speed of 1200 rpm to pelletization. After that, cells are re-translated into a slurry with a density of 275000 cells/ml in complete pitat the school environment (CM), containing 200 ng/ml of recombinant factor of human stem cells (SCF) (supplier: Peprotech, catalog No. 300-07) and 20 ng/ml human flt-3 ligand (supplier: Peprotech, catalog No. 300-19) (“CM/SCF/flt-3 (medium). On about the fourth or fifth day, the density of the culture was checked by counting cells and diluted in culture to a density of 275000 cells/ml of fresh nutrient medium, CM/SCF/flt-3 medium. About the seventh day of the culture was transferred into a sterile tube and count the cells. Cells were processed in a centrifuge at 1200 rpm and re-made into a slurry with a density of 275000 cells/ml in fresh culture medium, CM/SCF/flt-3 medium.

This cycle is repeated, starting from day 0, a total of from 3 to 5 times within a period of increasing population.

If necessary, re-transfer in the suspension of a large number of crops that are contained in multiple vials, the contents of all flasks were combined in a single vessel before counting cells. Thus, provided the accuracy of the counting of cells, as well as a unified approach to the entire population. Before you merge the contents of the flask were examined under a microscope for the presence of contamination to prevent possible contamination of the entire population.

Between the 17th and the 24th day of may deterioration of culture (i.e. dies from 5 to 10% of the t total number of cells) and the population growth slows down. During this period, the observation of the cells is carried out every day, because just the day culture can be completely destroyed. After the beginning of the deterioration of the cell count, treated in a centrifuge at 850 rpm for 15 min and re-transform into a slurry with a density of 350,000 cells/ml in complete culture medium CM/SCF/flt-3 medium, in order to get even one or two notches to the culture. For cells provide daily supervision in order to prevent the death of culture.

When the percentage of cell death culture of progenitor cells exceeds 15% in the culture notes the presence of a certain amount of decomposition products, CD34-negative precursor cells ready to differentiation.

7.2.1.3 Differentiation of CD34-negative progenitor cells in Metacity mucous

The second phase is to convert grown CD34-negative progenitor cells into differentiated mastocyte mucous. These mucous membranes of the cultured mastocyte person (“CHMS”) derived from CD34+cell isolated from umbilical cord blood and processed to produce a vast population of CD34-negative progenitor cells, as described above. To obtain the CD43-negative precursor cells cycle re-transfer in the suspension culture was identical visar is maintained, except that culture were sown with a density of 425000 cells/ml and on the fourth or fifth day was added about 15% of additional nutrient media without counting cells. In addition, cytokines the composition of the medium was changed so that it contains a factor of stem cells (200 ng/ml) and human recombinant IL-6 (200 ng/ml; supplier: Peprotech, catalog No. 200-06), restored to 100 μm/ml in sterile acetic acid (10 mm) (CM environment/SCF/IL-6”).

Phase I and II duration take about 5 weeks. Cell death and the presence of degradation products in the culture seen through from the first to the third week; in addition, from the second to the fifth week there is a period during which some part of the culture is already not in suspension and attached to the surface of the vessel in which it is grown culture.

As in phase I, if necessary, re-suspension culture on the seventh day of each cycle, the contents of all flasks were combined in a single vessel before counting the cells to ensure consistency among the entire population. Each flask was preliminarily examined under a microscope in order to detect contamination and to prevent contamination of the entire population.

When combining the contents of the flasks approximately 75% of the volume of the flask was poured into a common vessel, leaving in the flask for about 10 ml. and Then on to the forehead with the remaining liquid is sharply tapped in the transverse direction with the to release adherent to the cell surface. Re-tapping is made at right angles to the first, in order to finally budge cells.

Before pouring the remaining liquid in the vessel to calculate the flask was tilted at an angle of 45 degrees for a few minutes. Before seeding in the amount of 35-50 ml per flask (with density 425000 cells/ml) cells were processed in a centrifuge at 950 rpm for 15 minutes

7.2.1.4 Differentiation of CD34-negative progenitor cells in Metacity connective tissue

The increased population of CD34-negative progenitor cells prepared by the above method and processed with the aim of obtaining tryptase/hemato-positive phenotype (connective tissue). When used methods similar to the above for mastocytes mucous membranes, except for the addition of IL-4 instead of IL-6 in culture medium culture. The obtained cells typical of mastocytes connective tissue.

7.2.1.5 Differentiation of CD34-negative progenitor cells in basophils

Multiplied the population of CD34-negative progenitor cells prepared by the method described above in section 7.2.1.3, and used for the formation of an increased population of basophils. CD34-negative cells were processed according to the method similar) is defined above for mastocytes mucous membranes, except for the addition of IL-3 (20-50 ng/ml) instead of IL-6 in the culture medium of culture.

7.2.2 Activation CHMC (cultivated mastocyte person) with IgE at low density cells: analysis of tryptase and LTC4

In two 96-well round-bottom of the tablet (model Costar 3799) add 65 ál solutions of the prepared compounds or control samples prepared in the MT [137 mm NaCl, 2.7 mm KCl, 1.8 mm CaCl2,1.0 mm MgCl2, 5.6 mm glucose, 20 mm Hepes (N-2-hydroxyethylpiperazine-N-2-econsultancy acid) (pH of 7.4), 0.1% bovine albumin serum (Sigma A4503)], with 2% MeOH and 1% DMSO. Then follows the process of pelletization CHMC cells in a centrifuge (980 rpm, 10 min) and re-translation in suspension in a pre-heated environment of MT. Next pour in 65 μl of cells in each 96-well round-bottom plate. Depending on the degranulation activity of each individual donors CHMC put 1000-1500 cells in each well. Mix four times, followed by incubation for 1 hour at 37°C. for one hour required for incubation, prepare a solution of 6X anti-IgE [anti-human immunoglobulin rabbit IgE (1 mg/ml, supplier: Bethyl Laboratories, catalogue number A80-109A), diluted in a ratio of 1:167 in buffer solution MT]. Cells are stimulated by addition of 25 μl of a solution of 6X anti-IgE to the appropriate tablets. To the test tubes, not p is improper stimulation, add 25 ál of MT. After the addition of anti-IgE stirred twice. Incubated at 37°C for 30 minutes. During the 30-minute incubation dilute solution of 20 mm stock with substrate tryptase [(Z-Ala-Lys-Arg-AMC·TPUK; Enzyme Systems Products, #AMC-246)] 1:2000 in buffer solution for the quantitative analysis of tryptase [0.1 M Hepes (pH 7.5), 10% wt./about. glycerol, 10 μm heparin (Sigma H-4898) of 0.01% NaN3]. The tablets are treated in a centrifuge at 1000 rpm for 10 min to pelletization cells. Transfer 25 ál of the supernatant in a 96-well plate with a black bottom and add 100 µl freshly diluted solution of tryptase substrate to each well. Incubated for 30 minutes at room temperature. With the help of a spectrophotometer to read the tablets determine the optical density of the tablets at 355 nm/460 nm.

Quantitative analysis of leukotriene C4 (LTC4) is also carried out with the help of ELISA kits to properly diluted samples of the supernatant (determined empirically for a population of cells of each donor to the fact that the measurements of the samples were within the standard curve) according to the manufacturer's instructions.

7.2.3 Activation CHMC with IgE with high density of cells: analyses for degranulation (tryptase, histamine), leukotriene (LTC4) and cytokine (TNF, IL-13)

Cultivated mastocyte person (CHMC) sensibiliser during the AI 5 days with IL-4 (20 ng/ml), factor stem cells (200 ng/ml), IL-6 (200 ng/ml) and human IgE CP 1035K (supplier: Cortx Biochem, 100-500 ng/ml depending on generation) in the conditioned medium (CM). After sensitization of cells counted, processed in a centrifuge (1000 rpm, 5 to 10 minutes) and re-transformed into a suspension with a density of 1-2 ×106cells/ml in a buffer solution of MT. Add 100 ál of cell suspension into each well and 100 μl of solutions of the prepared formulations. The final concentration of the medium and 0.5% DMSO. Incubated at 37°C (5% CO2) for 1 hour. After an hour of processing reagents cells stimulate 6X anti-IgE. Tubes with cells mix and leave the tablet for incubation at 37°C (5% CO2) for one hour. After incubation for one hour, the cells are treated in a centrifuge (10 min, 1000 rpm) and select 200 μl of supernatant from each tube, while acting carefully, so as not to hurt the sediment. Tablet supernatant was placed on ice. When performing a 7-hour stage (see below) determine the activity of tryptase supernatant, diluted 1:500, re-suspended cells in 240 μl of medium CM,

containing 0.5% DMSO and the appropriate concentration. The CHMC cells incubated for 7 hours at 37°C (5% CO2). After incubation, the cells are centrifuged (1000 rpm, 10 minutes), select 225 ál from each tube and store the ri a temperature of -80°C to conduct ELISA assays. ELISA performed on appropriately diluted samples (determined empirically for a population of cells of each donor to the fact that the measurements of the samples were within the standard curve) according to the manufacturer's instructions.

7.2.4 Results

The results of the analysis populations CHMC low density are shown in table 1. All values in table 1 are expressed in the IC50(in μm). A large part of the analyzed compounds were IC50less than 10 μm, and many value IC50was observed in submicromolar range. All values in table 1 are expressed in the IC50(in μm). The sign “-” means that the IC50> 10 μm in the absence of any effects at concentrations of 10 μm, which could be measured. A large part of the analyzed compounds were IC50less than 10 μm, and many value IC50was observed in submicromolar range. The sign “+” means

IC50< 10 μm. Of the analyzed compounds value for BMMC were comparable with values observed in the case of CHMC.

7.3 Selective inhibition by compounds 2,4-pyrimidinediamine according to the present invention the reverse cascade IgE receptor

To confirm the fact that many compounds 2,4-pyrimidinediamine presented in the invention have the make their inhibitory ability by blocking or inhibiting the cascade transmission start signal IgE receptors some of the compounds were checked by the method of cellular analysis on the degranulation induced by ionomycin, as set forth below.

7.3.1 Activation CHMC low density ionomycin, analysis of tryptase

Analysis of degranulation mastocytes induced by ionomycin, was similar to the analysis of activation CHMC low density IgE (Section 7.2.2,above), except that during the incubation for 1 hour to prepare a solution of 6X ionomycin [5 mm ionomycin (Signma I-0634) in MeOH (basic solution), diluted in a ratio of 1:416,7 in MT-buffer (final concentration 2 μm)] and stimulated cells by the addition of 25 μl of a solution of 6X ionomycin in the appropriate tablets.

7.3.2 Results

The results of the analyses on the degranulation induced by ionomycin, presented in the form of indicators IC50(in µm)are shown in table 1. Of the analyzed active compounds (i.e., those which inhibit the degranulation induced by immunoglobulin IgE), a significant majority did not inhibit the degranulation induced by ionomycin, which confirms the selective inhibition data of the active compounds of the cascade transfer early (or reverse) signals IgE receptors. In table 1, all the values are IC50(in μm). The sign “-” means that the IC50> 10 μm in the absence of any doubt the impact at a concentration of 10 μm, which could be measured. The “+” sign means that the IC50< 10 μm.

7.4 Inhibition of Syk-kinase compounds 2,4-pyrimidinediamine in the process of biochemical tests

A series of compounds 2,4-pyrimidinediamine was analyzed to identify the ability to inhibition catalyzed Syk kinase phosphorylation of the substrate peptide by the method of biochemical analysis of fluorescence polarization with a dedicated Syk kinase. In this experiment, compounds were diluted to 1% DMSO in kinase buffer (20 mm HEPES, pH of 7.4, 5 mm MgCl2, 2 mm MnCl2, 1 mm dithiothreitol (DTT), 0.1 mg/ml acetylated bovine gamma globulin). The compound in 1% DMSO (0.2% DMSO final) was mixed with ATP/substrate solution at room temperature. Syk-kinase (Upstate, Lake Placid, NY) was added to a final reaction volume of 20 μl, and incubated the reaction for 30 minutes at room temperature. The final enzymatic reaction conditions: 20 mm HEPES, pH of 7.4, 5 mm

MgCl2, 2 mm MnCl2, 1 mm DTT, 0.1 mg/ml acetylated bovine gamma globulin, a 0.125 ng Syk-kinase, 4 mcm ATP (adenosine triphosphate), 2.5 μm peptide substrate (Biotin-EQEDEPEGDYEEVLE-CONH2, supplier: SynPep Corporation). EDTA (10 mm final concentration)/anti-phosphotyrosine antibody (1X - end)/fluorescent label phosphopeptide (0,5X - final) was added to the buffer solution postop is pted to terminate the reaction and obtain a total volume of 40 µl according to the manufacturer's instructions (firm Pan Vera Corporation). Tablet incubated for 30 minutes in the dark at room temperature. Tablets read on the device of fluorescence polarization for tablets "Polarion" (Polarion) company Tecan. Data were recalculated in accordance with the number of available phosphopeptide on the calibration curve from the competition with a competitor of phosphopeptide provided in the kit for the analysis of tyrosine kinase (green) (supplier: Pan Vera Corporation).

These data are shown in table 1, show that most of the investigated drugs inhibit phosphorylation of Syk-kinase with indicators of the IC50in submicromolar range. The vast majority of the investigated compounds inhibit phosphorylation of Syk-kinase with indicators of the IC50in the micromolar range. In table 1, all the values are IC50(in μm). The sign “-” means that the IC50> 10 μm in the absence of any effects at concentrations of 10 μm, which could be measured. The “+” sign means that the IC50< 10 μm.

5-fluoro-N2-(3-hydroxyphenyl)-N4-(3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,27(s, 1H), 9,18(s, 1H), 8,10(d, 1H, J=3,9 Hz), of 6.99(d, 2H, J=2.1 Hz), 6,92(d, 2H, J=2.4 Hz), 6,21(t, 1H, J=2.1 Hz), equal to 6.05(t, 1H, J=2.4 Hz), 3,68(s, 6H), 3,62(s, 6H); LC/MS: purity: 100%; MS(mass/charge): 401(MH+) td align="justify"> 1H NMR(CD3OD): d for 7.78(d, 1H, J=8,4 Hz), 7,07(users, 1H), of 6.96(users, 2H), 6.87 in(d, 2H, J=2.4 Hz), 6,10(t, 1H, J=2.4 Hz), 3,70(s, 6H), of 3.54(s, 3H), of 3.32(s, 3H), of 1.48(s, 6H); LC/MS: purity: 97%, MS(mass/charge): 468(MH+). LC/MS: purity: 80%, MS(mass/charge): 467(MH+). 455td align="justify"> -td align="justify"> - +
Table 1
Room
connection.
Connection namePhysical characteristicsLD Tryptase, CHMC, IgE, 3ptLD
Tryptase, CHMC, Iono, 3pt
fp_syk,
11pt
200(S)-5-fluoro-N2-(indazol-6-yl)-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR1(DMSO-d6): d 8,08 (d, 1H), 7,95(s, 1H), 7,58(d, 1H), 7,40(m, 1H), 7,25(m, 3H), 6,94(m, 1H), 4,80(m, 1H), 1,40(s, 3H); LC2/MC3: purity: 96%; MS(mass/charge): 406(MH+).+
201(S)-5-fluoro-N2-(1-methylindol-6-yl)-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 8,17(d, 1H), 8,08(s, 1H), 7,80(s, 1H), 7,52(m, 1H), 7,32(m, 1H),7,17(m, 2H), 6,94(m, 1H), 4,60(m, 1H), of 3.77(s, 3H), 1,45(s, 3H); LC/MS: purity: 94%; MS(mass/charge): 420(MH+).+
202(S)-N2-(3, 5dimethylphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 8,01(d, 1H), 7,28 (m, 2H), 7,20(s, 2H), 6,95(m, 1H), return of 6.58(s, 1H), 4,63(m, 1H), of 3.77(s, 3H), 2,07(s, 6H), of 1.42(d, 3H); LC/MS: purity: 92%; MS(mass/charge): 393(MH+). +
203N4-(3,4-Dihydro-3,3-dimethyl-2H,4H-benzo[1,4]oxazin-6-yl)-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 8,02(d, 1H), 6,98 (m, 2H), 6.90 to(m, 2H), to 6.80(m, 1H), 6,03 (s, 1H), and 3.72(s, 2H), 3,60 (s, 6H), of 1.05(s, 6H); LC/MS: purity: 96%; MS(mass/charge): 425(MH+).++
204(R)-N2-(3, 5dimethylphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 8,01(d, 1H), 7,28 (m, 2H), 7,20(s, 2H), 6,95(m, 1H), return of 6.58(s, 1H), 4,63(m, 1H), of 3.77(s, 3H), 2,07(s, 6H), of 1.42(d, 3H); LC/MS: purity: 92%; MS(mass/charge): 393(MH+).+
205(R)-5-fluoro-N2-[6-(2-hydroxyethyl)-2,3-dihydropyrrolo[1,2,3-d,e]benzoxazin-8-yl]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(MeOD-d4): d of 7.75(d, 1H), 7,38 (m, 1H), 7,02(m, 3H), 6,78(m, 2H), 4,54(m, 1H), 4,4 (m, 2H), 4,14(m, 2H), 3,62(m, 2H), 3,62(m, 2H), 2,80(m, 2H), 1,41(d, 3H); LC/MS: purity: 93%; MS(mass/charge): 491(MH+).+
206N4-(3,4-Dihydro-3,3-dimethyl-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[6-(2-hydroxyethyl)-2,3-dihydropyrrolo[1,2,3-d,e]benzoxazin-8-yl]-2,4-pyrimidinediamine1H NMR(MeOD-d4): d a 7.62(d, 1H),? 7.04 baby mortality (s, 1H), 6,98(m, 2H), 6.75 in(m, 1H), 6,59(m, 2H), 4,47(m, 1H), 4,4 (m, 2H), 4,14(m, 2H), 3,62(m, 4H), 2,80(m, 2H), with 1.07(s, 6H); LC/MS: purity: 98%; MS(mass/charge): 491(MH+).+
207(R)-N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine salt benzosulfimide acid1H NMR(MeOD-d4): d 7,98(d, 1H), 7,82 (m, 2H), of 7.48 (s, 1H), 7,41(m, 3H), 7,25(DD, 1H), 7,15(m, 3H), 6,94(d, 1H), 4,62(square, 1H), 3,82(s, 3H), of 1.50(d, 3H); LC/MS: purity: 97%; MS(mass/charge): 430(MH+).+
208(R)-N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine salt methanesulfonic acid1H NMR(MeOD-d4): d 7,98(d, 1H), of 7.48 (s, 1H), 7,25(DD, 1H), 7,15(m, 3H), 6,94(d, 1H), 4,62(square, 1H), 3,82(s, 3H), 2,68(s, 3H),of 1.50(d, 3H); LC/MS: purity: 98%; MS(mass/charge): 43(MH+). +
209(R)-N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine salt of (1S)-(+)-camphorsulfonic acid1H NMR(DMSO-d6): d 8,19(d, 1H), 7.62mm (m, 1H), 7,38 (m, 1H), 7,21(m, 1H), 7,12(m, 2H), 6,91(d, 1H), 4,62(square, 1H), 3,82(s, 3H), 3,40(square, 1H), 2.91 in(m, 1H), 2,61(m, 1H), of 2.38(m, 1H), 2,22(m, 1H), of 1.85(m, 2H), 1,40(d, 3H), 1,31(m, 2H), of 1.03(s, 3H), of 0.77 (s, 3H); LC/MS: purity: 97%; MS(mass/charge): 430(MH+).+
210(R)-5-fluoro-N2-(1-methylindol-6-yl)-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d is 8.16(d, 1H), 8,08(s, 1H), 7,80(s, 1H), 7,52(m, 1H), 7,32(m, 1H), 7,17(m, 2H), 6,94(m, 1H), 4,60(m, 1H), of 3.77(s, 3H), 1,45(s, 3H); LC/MS: purity: 97%; MS(mass/charge): 420(MH+).+
211(R)-N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine cleaners containing hydrochloride salt1H NMR(DMSO-d6): d to 8.12(d, 1H), 7,41(DD, 1H), 722(m, 3H), 6,97(m, 1H), br4.61(square, 1H), of 3.78(s, 3H), of 1.40(d, 3H); LC/MS: purity: 97%; MS(mass/charge): 430(MH+).++
212(R)-N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine salt of (1R)-(-)-camphorsulfonic acid1H NMR(DMSO-d6): d 8,19(d, 1H), 7.62mm (m, 1H), 7,38 (m, 1H), 7,21(m, 1H), 7,12(m, 2H), 6,91(d, 1H), 4,62(square, 1H), 3,82(s, 3H), 3,40(square, 1H), 2.91 in(m, 1H), 2,61(m, 1H), of 2.38(m, 1H), 2,22(m, 1H), of 1.85(m, 2H), 1,40(d, 3H), 1,31(m, 2H), of 1.03(s,3H), of 0.77 (s, 3H); LC/MS: purity: 98%; MS(mass/charge): 430(MH+).++
213(R)-N2-(3-Chloro-4-methoxy-6-were)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 8,17(s, 1H), 7,98(d, 1H), 7,43(m, 1H), 7,32(m, 1H), 7,15(s, 1H), 6,95(s, 1H), 6,72(d, 1H), 4,58(m, 1H), 3,90(s, 3H), 2,17(s, 3H), of 1.38(d, 3H); LC/MS: purity: 97%; MS(mass/charge): 444(MH+).++
214(S)-N2-(3-Chloro-4-methoxy-6-were)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-PIR is midengined 1H NMR(DMSO-d6): d 8,17(s, 1H), 7,98(d, 1H), 7,43(m, 1H), 7,32(m, 1H), 7,15(s, 1H), 6,95(s, 1H), 6,72(d, 1H), 4,58(m, 1H), 3,90(s, 3H), 2,17(s, 3H), of 1.38(d, 3H); LC/MS: purity: 99%; MS(mass/charge): 444(MH+).++-
215(S)-(3-Chloro-4,6-acid)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 1.38(d, 3H), 3,82(s, 3H), 3,90(s, 3H), 4,58(square, 1H), 6,85 (m, 2H), 7,19(m, 1H), 7,37(m, 1H), 7,43(m, 1H), to 7.59(s, 1H), 8,17(m, 2H) purity: 99%; MS(mass/charge): 460(MH+).++-
216N2-(3-Chloro-4-methoxy-6-were)-N4-(3,4-dihydro-3,3-dimethyl-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 1.38(s, 6H), 2,17(s, 3H), of 3.64(s, 3H), 3,81 (s, 3H), 6.48 in (m, 1H), 6,77 (m, 1H), 6,93 (m, 1H), 6,99 (m, 1H), 7,41 (s, 1H), 7,82 (d, 1H) purity: 99%; MS(mass/charge): 444(MH+).++-
217N4-(3,4-Dihydro-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1 H NMR(DMSO-d6): d 8,19(m, 1H), 8,15(d, 1H), 7,78(m, 1H), 7,39(m, 2H), 6.90 to(m, 1H), 6,47(m, 1H), 4,07(m, 2H), up 3.22(m, 2H); LC/MS: purity: 97%; MS(mass/charge): 405(MH+).++-
218N4-(3,4-Dihydro-3,3-dimethyl-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.18(s, 6H), 3,81 (s, 2H), 6,77 (m, 1H), 6,93 (m, 1H), 6,99 (m, 1H), 7,38 (m, 2H), 7,63 (m, 1H), 7,71 (m, 1H), 8,12 (s, 1H), they were 8.22 (m, 2H) purity: 99%; MS(mass/charge): 433(MH+).++-
2195-fluoro-N2-[3-(oxazol-2-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 4,50(s, 2H), 6,78 (m, 1H), 7,18 (m, 1H), 7.23 percent(m, 1H), 7,38 (m, 2H), to 7.59 (m, 1H), to 7.77 (m, 1H), they were 8.22 (m, 3H) purity: 99%; MS(mass/charge): 419(MH+).++-
2205-fluoro-N2-[3-(oxazol-2-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-7-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 4,50 (s, 2H), 6,78 (m, 1H), 7,18 (m, 1H), 7.23 percent(m, 1H), 7,41 (m, 2H), to 7.59 (m, 1H), 7,78 (m, 1H), they were 8.22 (m, 3H) purity: 97%; MS(massacared): 419(MH+). ++-
2215-fluoro-N4-[2-(2-hydroxyethyl)-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl]-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 1.98(m, 1H), to 3.58(m, 2H), 6,78 (m, 1H), 7,18 (m, 1H), 7,38 (m, 3H), EUR 7.57 (m, 1H), 7,79 (m, 1H), they were 8.22 (m, 2H) purity: 99%; MS(mass/charge): 463(MH+).++-
222N4-(3,4-Dihydro-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 8,29(m, 1H), 8,17(d, 1H), 7,76(m, 1H), to 7.59(m, 3H), 6.90 to(m, 1H), 6,77(m, 1H), 6,62(m, 1H), 4,07(m, 2H), up 3.22(m, 2H); LC/MS: purity: 90%; MS(mass/charge): 405(MH+).++-
223N4-(3,4-Dihydro-3,3-dimethyl-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.18 (s, 6H), 3,80(s, 2H), of 6.71 (m, 2H), 6,95 (m, 1H), 7,51 (s, 1H), 7,69 (m, 2H), 7,69 (m, 2H), to 8.20 (d, 1H), scored 8.38 (s, 1H) purity: 95%; MS(mass/charge): 433(MH+).++ -
2245-fluoro-N2-[4-(oxazol-5-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d and 4.68(s, 2H), 6,98 (m, 2H), 7,22 (m, 1H), 7,51 (s, 1H), EUR 7.57 (m, 2H), 7,78 (m, 2H), 8,28 (d, 1H), scored 8.38 (s, 1H) purity: 98%; MS(mass/charge): 419(MH+).++-
225(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[4-(oxazol-5-ylphenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 8.28(s, 1H), they were 8.22(d, 1H), 7.62mm(m, 2H), EUR 7.57(m, 2H), 7,49(s, 1H), 7,25(m, 2H), 6,98(m, 1H), 4,62(square, 1H), of 1.42(d, 3H); LC/MS: purity: 88%; MS(mass/charge): 433(MH+).++-
2265-fluoro-N2-[4-(oxazol-5-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-7-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 4.66(s, 2H), 6,98 (m, 2H), 7,22 (m, 1H), 7,51 (s, 1H), EUR 7.57 (m, 2H), 7,76 (m, 2H), 8,28 (d, 1H), scored 8.38 (s, 1H) purity: 92%; MS(mass/charge): 419(MH+).++-
2275-fluoro-N4-[2-(2-what hydroxyethyl)-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl]-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d of 1.93(m, 2H), to 3.58 (m, 2H), to 4.62(m, 1H), 6,98 (m, 2H), 7,22 (m, 2H), 7,51 (s, 1H), EUR 7.57 (m, 2H), 7,76 (m, 2H), 8,28 (d, 1H), scored 8.38 (s, 1H) purity: 95%; MS(mass/charge): 463(MH+).++-
228N4-(3,4-Dihydro-4-methyl-2H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 8,29(s, 1H), 8,15(d, 1H), 7,76(m, 1H), EUR 7.57(m, 3H), to 6.88(m, 1H), 6,77(m, 1H), 6,62(m, 1H), 4,10(m, 2H), 3,20(m, 2H), 2,80(s, 3H); LC/MS: purity: 94%; MS(mass/charge): 419(MH+).++-
229N4-(3,4-Dihydro-4-methyl-2H-benzo[1,4]oxazin-7-yl)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 8.37(s, 1H), 8,19(d, 1H), to 7.61(m, 5H), 7,07(m, 2H), of 6.68(m, 1H), 4,22(m, 2H), up 3.22(m, 2H), of 2.81(s, 3H); LC/MS: purity: 94%; MS(mass/charge): 419(MH+).++-
2305-fluoro-N4-(4-methyl-3-oxo-2H-benzo[1,4]oxazin-7-yl)-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d at 8.36(s, 1H), 8,0(m, 1H), 8,19(d, 1H), to 7.77(m, 2H), 7,54(m, 2H), 7,37(s, 1H), 7,25(m, 1H), 6,97(m, 1H), 4,58(s, 2H), 2,97(s, 3H); LC/MS: purity: 98%; MS(mass/charge): 433(MH+).---
2315-fluoro-N4-(4-methyl-3-oxo-2H-benzo[1,4]oxazin-6-yl)-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 8.34(s, 1H), to 8.20(m, 1H), 8,17(d, 1H), 7,71(m, 2H), 7,54(m, 2H), 7,33(s, 1H), 7,25(m, 1H), 6,92(m, 1H), 4,60(s, 2H), 2,90(s, 3H); LC/MS: purity: 95%; MS(mass/charge): 433(MH+).---
232N4-(3,4-Dihydro-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 8,39(m, 1H), they were 8.22(d, 1H), 7,86(m, 1H), to 7.59(m, 4H), 6.87 in(m, 2H), of 6.52(m, 1H), 4.09 to(m, 2H), 3,23(m, 2H); LC/MS: purity: 90%; MS(mass/charge): 405(MH+).++-
233N4-(3,4-Dihydro-3,3-dimethyl-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 8.37(s, 1H), 8,19(d, 1H), 7,82(m, 1H), 7,63(m, 2H), 7,50(s, 1H), 7,38(m, 1H), 6.87 in(m, 1H), 6,65(m, 2), is 3.82(s, 2H), 1,19(s, 6H); LC/MS: purity: 95%; MS(mass/charge): 433(MH+).++-
2345-fluoro-N2-[3-(oxazol-5-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-7-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d was 4.42 (s, 2H), is 6.61 (m, 2H), 6,95 (m, 1H), 7,51 (s, 1H), 7,49 (m, 2H), to 7.59 (m, 2H), to 8.20 (d, 1H), scored 8.38 (s, 1H) purity: 90%; MS(mass/charge): 419(MH+).++-
2355-fluoro-N4-[2-(2-hydroxyethyl)-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl]-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.93(m, 2H), to 3.58 (m, 2H), to 4.62(m, 1H), 6,61 (m, 2H), 6,95 (m, 1H), 7,51 (s, 1H), 7,49 (m, 2H), to 7.59 (m, 2H), to 8.20 (d, 1H), scored 8.38 (s, 1H) purity: 90%; MS(mass/charge): 463(MH+).++-
236N4-(3,4-Dihydro-4-methyl-2H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.93(m, 2H), to 3.58 (m, 2H), to 4.62(m, 1H), 6,61 (m, 2H), 6,95 (m, 1H), 7,51 (s, 1H), 7,49 (m, 2H), to 7.59 (m, 2H), to 8.20 (d, 1H), scored 8.38 (s, 1H) purity: 95%; MS(mass/charge): 419(MH+). +-
237N4-(3,4-Dihydro-4-methyl-2H-benzo[1,4]oxazin-7-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.93(m, 2H), 2,82(s, 3H), to 3.58 (m, 2H), to 4.62(m, 1H), 6,61 (m, 2H), 6,95 (m, 1H), 7,51 (s, 1H), 7,49 (m, 2H), to 7.59 (m, 2H), to 8.20 (d, 1H), scored 8.38 (s, 1H) purity: 95%; MS(mass/charge): 419(MH+).+-
238N4-(3,4-Dihydro-3,3-dimethyl-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 1.38(s, 6H), 3,81 (s, 2H), of 6.71 (m, 2H), 6,95 (m, 1H), 7,51 (s, 1H), 7,69 (m, 2H), 7,69 (m, 2H), to 8.20 (d, 1H), scored 8.38 (s, 1H) purity: 99%; MS(mass/charge): 433(MH+).++-
2395-fluoro-N2-[4-(oxazol-2-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 8.15(d, 1H), 8,10(s, 1H), 7,78(m, 3H), 7,14(m, 3H), 6,97(m, 2H), 4,56(s, 2H); LC/MS: purity: 98%; MS(mass/charge): 419(MH+).++-
240(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 8.25(m, 1H), they were 8.22(d, 1H), 8,12(m, 1H), to 7.77(m, 2H), 7,34(s, 1H), 7.23 percent(m, 2H), 6,98(m, 2H), 4,63(square, 1H), of 1.42(d, 3H); LC/MS: purity: 95%; MS(mass/charge): 433(MH+).++-
2415-fluoro-N2-[4-(oxazol-2-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-7-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 4.45 (s, 2H), of 6.71 (m, 2H), 6,95 (m, 1H), 7,51 (s, 1H), 7,69 (m, 2H), 7,69 (m, 2H), to 8.20 (d, 1H), scored 8.38 (s, 1H) purity: 95%; MS(mass/charge): 419(MH+).--
2425-fluoro-N4-[2-(2-hydroxyethyl)-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl]-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 8.25(d, 1H), to 8.20(d, 1H), 8,16(s, 1H), 7,82(m, 3H), 7,35 (s, 1H), 7,20(m, 2H), 6,95(m, 1H), to 4.62 (m, 1H), to 3.58(m, 1H), 1,95(m, 2H); LC/MS: purity: 99%; MS(mass/charge): 463(MH+).++-
2434-(2,3-Dihydro-4-methyl-2H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d of 1.93(m, 2H), 2,80(s, 3H), to 3.58 (m, 2H), to 4.62(m, 1H), of 6.71 (m, 2H), 6,95 (m, 1H), 7,51 (s, 1H), 7,69 (m, 2H), 7,69 (m, 2H), to 8.20 (d, 1H), scored 8.38 (s, 1H) purity: 99%; MS(mass/charge): 419(MH+).++-
2445-fluoro-N4-(4-methyl-3-oxo-2H-benzo[1,4]oxazin-7-yl)-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 8,18(d, 1H), 8,14(s, 1H), 7,82(d, 2H), 7,56(m, 2H), 7,40(m, 2H), 7,30(s, 1H), 6,95(m, 1H), to 4.62 (s, 2H), 2,78(s, 3H); LC/MS: purity: 99%; MS(mass/charge): 433(MH+).--
2455-fluoro-N4-(4-methyl-3-oxo-2H-benzo[1,4]oxazin-6-yl)-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 8.20(d, 1H), 8,12(s, 1H), 7,82(d, 2H), 7,55(m, 2H), 7,40(m, 2H), 7,33(s, 1H), to 6.88(m, 1H), 4,59 (s, 2H), 2,77(s, 3H); LC/MS: purity: 98%; MS(mass/charge): 433(MH+).--
2465-fluoro-N2-[3-(oxazol-5-yl)phenyl]-N4-[3-oxo-2H,4H-benzo[1,4]oxazin-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 4.45 (s, 2H), 6,78 (m, 1H), 7,18 (m, 1), 7,38 (m, 3H), EUR 7.57 (m, 1H), 7,79 (m, 1H), they were 8.22 (m, 2H) purity: 93%; MS(mass/charge): 419(MH+).++-
247(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 1.38(d, 3H), 4,58(square, 1H), 6,78 (m, 1H), 7,18 (m, 1H), 7,38 (m, 3H), EUR 7.57 (m, 1H), 7,79 (m, 1H), they were 8.22 (m, 2H) purity: 90%; MS(mass/charge): 433(MH+).++-
2485-fluoro-N4-[2-(2-hydroxyethyl)-3-oxo-2H,4H-benzo[1,4]oxazin-7-yl]-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.93(m, 2H), to 3.58 (m, 2H), to 4.62(m, 1H), to 6.88 (m, 2H), 7,22 (m, 3H), EUR 7.57 (m, 2H), 7,79 (m, 2H), by 8.22 (m, 2H) purity: 99%; MS(mass/charge): 463(MH+).++-
2495-fluoro-N4-[2-(2-hydroxyethyl)-3-oxo-2H,4H-benzo[1,4]oxazin-7-yl]-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.93(m, 2H), to 3.58 (m, 2H), to 4.62(m, 1H), of 6.71 (m, 2H), 6,95 (m, 1H), 7,51 (s, 1H), 7,69 (m, 2H), 7,69 (m, 2H), to 8.20 (d, 1H), scored 8.38 (s, 1H) purity: 99%; MS(mass/charge): 463(MH+). +--
250(R)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[3-(oxazol-4-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d d to 1.38(d, 3H), 4,58(square, 1H), to 6.88 (m, 1H), 7,22 (m, 4H), EUR 7.57 (m, 1H), 7,99 (m, 2H), 8,12 (m, 2H) purity: 95%; MS(mass/charge): 433(MH+).+++
251(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[3-(oxazol-4-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d d to 1.38(d, 3H), 4,58(square, 1H), to 6.88 (m, 1H), 7,22 (m, 4H), EUR 7.57 (m, 1H), 7,99 (m, 2H), 8,12 (m, 2H) purity: 99%; MS(mass/charge): 433(MH+).++-
252(R,S)-N2-(3, 5dimethylphenyl)-5-fluoro-N4-(tetrahydrofuran[2,3]-2H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 2.18(s, 6H), of 2.25(m, 2H) 3,75(t, 2H) 4,58(square, 1H), of 6.52 (d, 1H), 6,92 (DD, 2H), 7,37(m, 3H), 8,12 (d, 1H) purity: 90%; MS(mass/charge): 406(MH+).+
253N4-[3,4-Dihydro-2-(2-hydroxyethyl)-2H,4H-benzo[1,4]oxazin-6-yl]-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.88(m, 2H), 2,97(m, 2H), 3,55(m, 2H), 3,61(s, 6H), 4,08(square, 1H), 6,02 (m, 1H), return of 6.58 (d, 1H), of 6.96(m, 5H), 8,02 (d, 1H) purity: 96%; MS(mass/charge): 442(MH+).++-
2545-fluoro-N2-[3-(N-methylamino)carbonintensity]-N4-(3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 2,62(d, 3H), of 3.32 (s, 2H), 4,37(s, 2H), 6,60(m, 1H), 7,22(m, 3H), 7,37(m, 1H), 7,43 (m, 1H), 8,02(m, 1H), they were 8.22 (d, 1H) purity: 94%; MS(mass/charge): 455(MH+).++-
255N4-[2,3-Dihydro-2-(2-hydroxyethyl)-2H,4H-benzo[1,4]oxazin-6-yl]-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.88(m, 2H), 2,18 (s, 6H), of 2.97(m, 2H), to 3.58(m, 2H), 4.09 to(square, 1H), to 6.19 (m, 1H), 6.42 per(m, 1H), return of 6.58 (m, 1H), for 6.81 (m, 2H), 7,22(s, 2H), 8,02 (d, 1H) purity: 97%; MS(mass/charge): 410(MH+).++-
256N2-(3,5-Di is ethoxyphenyl)-5-fluoro-N4-(3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 3,37(s, 2H), 3,61(s, 6H), 6,18(m, 1H), 6.75 in(m, 2H), 7,22(m, 2H), 7,43 (m, 1H), they were 8.22 (d, 1H) purity: 98%; MS(mass/charge): 428(MH+).++-
257N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 3,47(s, 2H), 3,88(s, 3H), was 7.08(m, 1H), 7,25(s, 2H), 7,42(m, 2H), 7,78 (m, 1H), they were 8.22 (d, 1H) purity: 99%; MS(mass/charge): 432(MH+).++-
258N4-(3,4-Dihydro-2H,4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 2.67(d, 3H), of 3.32 (m, 2H), 4,30(s, 2H), 4,37(m, 2H), 6,45(m, 1H), to 6.88(m, 1H), of 6.96(m, 2H), 7,13(m, 1H), 7.23 percent(m, 2H), 8,02(m, 2H) purity: 92%; MS(mass/charge): 441(MH+).++-
2595-fluoro-N2-[3-(N-methylamino)carbonintensity]-N4-(4-methyl-3-oxo-2H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 2,62(d, 3H), 3,11(s, 3H), of 3.32 (s, 2H), 4,37(s, 2H), 6,60(m, 1H), 7,22(m, 3H), 737(m, 1H), the 7.43 (m, 1H), 8,02(m, 1H), they were 8.22 (d, 1H) purity: 95%; MS(mass/charge): 469(MH+).++-
260N2-(3,5-Acid)-5-fluoro-N4-(4-methyl-3-oxo-2H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 3,11(s, 3H), of 3.32 (s, 2H), to 3.58 (s, 6H), 6,18(m, 1H), 6.75 in(m, 2H), 7,32(m, 3H), 7,63 (m, 2H), by 8.22 (d, 1H) purity: 98%; MS(mass/charge): 442(MH+).++-
261N2-(3-Benzothioate)-5-fluoro-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 4,58 (s, 2H), 6,98(m, 1H), 7,19 (m, 2H), 7,39(m, 3H), of 7.93 (m, 1H), 8,19 (d, 1H) purity: 90%; MS(mass/charge): 411(MH+).+-
262N2-(3-Benzothioate)-5-fluoro-N4-[2-(2-hydroxyethyl)-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): 1,91(m, 2H), 3,54 (m, 2H), 4,63(m, 1H), 6,98(m, 1H), 7,19 (m, 2H), 7,39(m, 3H), of 7.93 (m, 1H), 8,19 (d, 1H) purity: 93%; MS(mass/charge): 455 (MH+).+
263N2-(3,5-Acid)-N4-(dioxide-2-methyl-1,1,3-trioxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.42(d, 3H), 3,63(s, 6H), 4,69(square, 1H), 6,14(s, 1H), 6,92(m, 2H), 7,72(s, 2H), 7,92(m, 2H), of 8.27(d, 1H) purity: 99%; MS(mass/charge): 474(MH+).++
264N2-(3, 5dimethylphenyl)-5-fluoro-N4-(2-methyl-1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.42(d, 3H), of 2.18(s, 6H), 4.72 in(square, 1H), only 6.64(m, 1H), 7,21(m, 2H), 7,72(s, 2H), 7,68(m, 2H), of 8.27(d, 1H) purity: 99%; MS(mass/charge): 442(MH+).++
2655-fluoro-N2-(indazol-6-yl)-N4-(2-methyl-1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.42(d, 3H), 4,79(square, 1H), 7.23 percent(m, 1H), 7,60(m, 1H), to 7.77(m, 1H), 7,82(m, 3H), 8,16(m, 1H), 8,27(d, 1H) purity: 94%; MS(mass/charge): 454(MH+).++
2665-fluoro-N4-(2-methyl-1,1,3-t is ioxo-2H,4H-benzo[1,4]thiazin-6-yl)-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d of 1.42(d, 3H), 3,66(s, 9H), 4,70(square, 1H),? 7.04 baby mortality(m, 2H), 7,72(s, 2H), 7,72(m, 3H), by 8.22(d, 1H) purity: 96%; MS(mass/charge): 504(MH+).++
267N2-(3,5-Acid)-N4-(2,2-dimethyl-1,1,3-trioxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time 12,32 min, purity: 100%; MS(mass/charge): 488(MH+)+
268N2-(3, 5dimethylphenyl)-N4-(2,2-dimethyl-1,1,3-trioxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time 13,35 min, purity: 99%; MS(mass/charge): 456(MH+)+
269N4-(2,2-Dimethyl-1,1,3-trioxo-4H-benzo[thiazin-6-yl)-5-fluoro-2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time 11,28 min, purity: 99%; MS(mass/charge): 518(MH+)+
270N2-(3,5-Acid)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time of 11.69 min, purity: 95%; MS(mass/charge): 442(MH+)+
271N2-(3, 5dimethylphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time of 12.12 min, purity: 98%; MS(mass/charge): 410(MH+)+
2725-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time 10,44 min, purity: 99%; MS(mass/charge): 472 (MH+)+
273N4-(2,2-Dimethyl-1,1,3-trioxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-(indazol-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 10,49 min, purity: 95%; MS(mass/charge): 468(MH+) +
274N4-(2,2-Dimethyl-1,1,3-trioxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-(indazol-5-yl)-2,4-pyrimidinediamineLC/MS: retention time 8,66 min, purity: 96%; MS(mass/charge): 468(MH+)+
275N4-(2,2-Dimethyl-1,1,3-trioxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamineLC/MS: retention time of 10.16 min, purity: 93%; MS(mass/charge): 515(MH+)+
276N2-(3-Chloro-4-methoxyphenyl)-N4-(2,2-dimethyl-1,1,3-trioxo-4H-benzo[thiazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time 12,66 min, purity: 99%; MS(mass/charge): 492(MH+)+
2775-fluoro-N2-(indazol-6-yl)-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidine is Jamin LC/MS: retention time 9,40 min, purity: 95%; MS(mass/charge): 422(MH+)+
2785-fluoro-N2-(indazol-5-yl)-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 8,23 min, purity: 98%; MS(mass/charge): 422(MH+)+
2795-fluoro-N2-[3-(N-methylamino)carbonintensity]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time of 9.51 min, purity: 96%; MS(mass/charge): 469(MH+)+
280N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 11,77 min, purity: 97%; MS(mass/charge): 446(MH+)+
281LC/MS: retention time 8,18 min, purity: 99%; MS(mass/charge): 384(MH+)++
282Racemic-5-fluoro-N2-(3-hydroxyphenyl)-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 9,11 min, purity: 99%; MS(mass/charge): 398(MH+)+
283Racemic-N4-(2,2-dimethyl-1,1,3-trioxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-[3-hydroxyphenyl]-2,4-pyrimidinediamineLC/MS: retention time of 9.89 min, purity: 99%; MS(mass/charge): 444(MH+)+
284Racemic-5-fluoro-N2-[3-hydroxyphenyl]-N4-(2-methyl-1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time was 9.33 min, purity: 97%; MS(mass/charge): 430(MH+)
285Racemic-5-fluoro-N2-[3-(N-methylamine)carbonintensity]-N4-(2-methyl-1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 9,44 min, purity: 93%; MS(mass/charge): 501(MH+)+
286Racemic-N2-(3-chloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 11,68 min, purity: 95%; MS(mass/charge): 478(MH+)+
2875-fluoro-N4-(3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time 9,49 min, purity: 99%; MS(mass/charge): 458(MH+)+
2885-fluoro-N2-(indazol-5-yl)-N4-(3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine LC/MS: retention time 7,28 min, purity: 98%; MS(mass/charge): 408(MH+)+
289N2-(3-Chloro-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[thiazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time 12,45 min, purity: 97%; MS(mass/charge): 460(MH+)+
290N2-(3,5-Acid)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time 12,81 min, purity: 99%; MS(mass/charge): 456(MH+)+
291N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]thiazin-6-yl)-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time 13,44 min, purity: 99%; MS(mass/charge): 424(MH+)+
292N4-(2,2-dimethyl-3-ox is-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine LC/MS: retention time up 11,86 min, purity: 99%; MS(mass/charge): 486(MH+)+
293N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time accounted for 10.39 min, purity: 99%; MS(mass/charge): 412(MH+)+
294N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamineLC/MS: retention time 10,04 min, purity: 97%; MS(mass/charge): 483(MH+)++
295N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-(indazol-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 10,54 min, purity: 96%; MS(mass/charge): 436(MH+)++
296 Racemic-5-fluoro-N2-(3-fluoro-4-methoxyphenyl)-N4-(2-methyl-1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 11,91 min, purity: 96%; MS(mass/charge): 462(MH+)++
297N4-(2,2-Dimethyl-1,1,3-trioxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-(3-fluoro-4-methoxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time 12,11 min, purity: 96%; MS(mass/charge): 476(MH+)++
298Racemic-5-fluoro-N2-(3-fluoro-4-methoxyphenyl)-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time of 11.29 min, purity: 98%; MS(mass/charge): 430(MH+)++
299N4-(2,2-Dimethyl-3-oxo-4H-benzo[thiazin-6-yl)-5-fluoro-N2-(3-fluoro-4-methoxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time 12,14 min, purity: 99%; MS(mass/charge): 444(MH+) ++
3005-fluoro-N2-(3-fluoro-4-methoxyphenyl)-N4-(3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 10,56 min, purity: 97%; MS(mass/charge): 415(MH+)++
301N2-(3, 5dimethylphenyl)-5-fluoro-N4-(3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 11,76 min, purity: 98%; MS(mass/charge): 396(MH+)++
302N2-(3, 5dimethylphenyl)-5-fluoro-N4-(1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time of 10.72 min, purity: 96%; MS(mass/charge): 428(MH+)+
303N2-(3,5-Acid)-5-fluoro-N4-(1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: time hold is of 10,06 min, purity: 95%; MS(mass/charge): 460(MH+)+
304N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 10,13 min, purity: 97%; MS(mass/charge): 464(MH+)+
3055-fluoro-N2-[3-(N-methylamino)carbonintensity]-N4-(1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time of 8.40 min, purity: 97%; MS(mass/charge): 487(MH+)+
3065-fluoro-N2-(3,4,5-trimethoxyphenyl)-N4-(1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 9,19 min, purity: 95%; MS(mass/charge): 490(MH+)+
3075-fluoro-N2-(indazol-6-yl)-N4-(1,1,3-three the CSR-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamine LC/MS: retention time of 8.33 min, purity: 91%; MS(mass/charge): 440(MH+)+
3085-fluoro-N2-(3-hydroxyphenyl)-N4-(1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 8,07 min, purity: 96%; MS(mass/charge): 416(MH+)+
3095-fluoro-N2-(3-fluoro-4-methoxyphenyl)-N4-(1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 9,74 min, purity: 95%; MS(mass/charge): 448(MH+)+
3105-fluoro-N2-(indazol-5-yl)-N4-(1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time 7,40 min, purity: 94%; MS(mass/charge): 440(MH+)+
311N4-(2,2-Di is ethyl-3-oxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-(1-methylindol-6-yl)-2,4-pyrimidinediamine LC/MS: retention time 10,15 min, purity: 99%; MS(mass/charge): 450(MH+)++
312N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-N2-(indazol-6-yl)-2,4-pyrimidinediamine triptorelinLC/MS: retention time 10,54 min, purity: 100%; MS(mass/charge): 436(MH+)
313N2-Chloro-5-fluoro-N4-(3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-4-pyrimidinamineLC/MS: retention time to 5.58 min, purity: 95%; MS(mass/charge): 311(MH+)+
314Racemic-N2-chloro-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-4-pyrimidinamineLC/MS: retention time 11,18 min, purity: 95%; MS(mass/charge): 325(MH+)+
315N2-Chloro-5-FPO is-N4-(1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-4-pyrimidinamine LC/MS: retention time there is a 10.03 min, purity: 95%; MS(mass/charge): 343(MH+)-
316N2-Chloro-N4-(2,2,-dimethyl-3-oxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-4-pyrimidinamineLC/MS: retention time 12,29 min, purity: 95%; MS(mass/charge): 339(MH+)+
317Racemic-N2-chloro-5-fluoro-N4-(2-methyl-1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-4-pyrimidinamineLC/MS: retention time of 10.16 min, purity: 96%; MS(mass/charge): 357(MH+)-
318N2-Chloro-N4-(2,2-dimethyl-1,1,3-trioxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-4-pyrimidinamineLC/MS: retention time of 10.50 min, purity: 96%; MS(mass/charge): 371(MH+)+
319N4-[benzoxazin-34H)-on-6-yl]2-chloro-5-fluoro-4-pyrimidinamine LC/MS: retention time 6,40 min, purity: 99%; MS(mass/charge): 296(MH+)+
320N2-Chloro-N4-(3,3-dimethyl-1,4-benzoxazin-6-yl)-5-torpedinidaeLC/MS: retention time 12,20 min, purity 99% MS(mass/charge): 309(MH+)+
324N2-(3,5-Acid)-5-fluoro-N4-(3-trifloromethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.57(users, 1H), of 9.21(users, 1H), 8,16(d, J=3.6 Hz, 1H), 8,01(d, J=8,1 Hz, 1H), of 7.75(s, 1H), 7,40(t, J=8,1 Hz, 1H), 7,01(d, J=8,4 Hz, 1H), 6,91(d, J=2.1 Hz, 2H), 6,09-the 6.06(m, 1H), 3,65(s, 6H); 19F NMR(282 MHz, DMSO-d6): -57,17, -163,27; LC/MS: purity: 99%; MS(mass/charge): 425(MH+)+
325N2-(3, 5dimethylphenyl)-5-fluoro-N4-(3-trifloromethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,54(users, 1H), 9,12(users, 1H), 8,15(DD, J=1.8 and 3.6 Hz, 1H), of 7.96(d, J=8,1 Hz, 1H), of 7.75(s, 1H), 7,41(t, J=8,1 Hz, 1H), 7,01(d, J=8,1 Hz, 1H), 6,55(s, 1H), 2,18(s, 6H); 19F NMR(282 MHz,DMSO-d6): -57,01, -163,96; LC/MS: purity: 99%; MS(mass/charge): 393(MH+).+
3265-fluoro-N2-(indol-6-yl)-N4-(3-trifloromethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,83(users, 1H), 9,49(s, 1H), 9,11(s, 1H), 8,13(DD, J=1.2 and 3.3 Hz, 1H), with 8.05(d, J=8,1 Hz, 1H), 7,80(d, J=13,2 Hz, 2H), 7,40-to 7.32(m, 2H), 7,21-7,16(m, 2H), 6,99-to 6.95(m, 1H), 6,34-6,28(m, 1H); 19F NMR(282 MHz, DMSO-d6): -57,14, -164,68; LC/MS: purity: 99%; MS(mass/charge): 404(MH+).++
3275-fluoro-N4-[1-(N-methylamino)carbanilide-6-yl]-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,87(users, 1H), being 9.61(s, 1H), 9,46-9,43(m, 1H), 8,08(d, J=3.6 Hz, 1H), 8,04-7,98(m, 1H), 7,40-7,25(m, 4H), 7,02(DD, J=1,8 and 8.4 Hz, 1H), 6,95-of 6.90(m, 1H), 6,77-6,70(m, 2H), 6,38 to 6.35(m, 1H), 4,39(s, 2H), 2,62(d, J=4,8 Hz, 3H), 2,48 (d, J=4,6 Hz, 3H); LC/MS: purity: 96%; MS(mass/charge): 464(MH+).+
328N2-(3,5-Acid)-N4-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,15(users, 1H), 9,11(s, 1H), 8,07(d, J=3,9 Hz, 1H), 7,37(s, 2H), 6.89 in(d, J=1,81 Hz, 2H), of 6.68(s, 1H), equal to 6.05(t, J=2.1 Hz, 1H), 3,61(s, 6H), of 2.23(s, 6H); 19F NMR(282 MHz, DMSO-d6): -163,60; LC/MS: purity: 99%; MS(mass/charge): 369(MH+
329N4-(3, 5dimethylphenyl)-5-fluoro-N2-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.45(s, 1H), which 9.22(s, 1H), 8,12(d, J=3,9 Hz, 1H), 7.68 per-to 7.64(m, 1H), 7,58-rate of 7.54(m, 1H), 7,33(s, 2H), of 6.71(s, 2H), 3,69(s, 3H), of 2.23(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 407(MH+).+
330N4-(3, 5dimethylphenyl)-5-fluoro-N4-(3-methyl-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,11(users, 1H), 9,94(users, 1H), 8,25(d, J=4,8 Hz, 1H), to 7.67(s, 2H), 7,24(s, 2H), 7,14(s, 1H), 6,80(s, 1H, in), 2.25(s, 3H), of 2.21(s, 6H); 19F NMR(282 MHz, DMSO-d6): -61,76, -161,10; LC/MS: purity: 99%; MS(mass/charge): 390(M+).+
331N2-(3, 5dimethylphenyl)-5-fluoro-N4-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine1H NMR(d6): d 9,86(users, 1H), 9,42(users, 1H), to 8.20(d, J=4,2 Hz, 1H), 7,80-7,76(m, 1H), 7,56-7,51(m, 1H), 7,18(s, 2H), 6,94(s, 1H), 6,59(s, 1H), 3,74(s, 3H), of 2.15(s, 6H); LC/MS: purity: 97%; MS(mass/charge): 407(MH+).+
332N2-(3,5-Acid)-5-fluoro-N4-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,59(users, 1H), 9,24(users, 1H), 8,18(d, J=3.3 Hz, 1H), 7,84-to 7.68(m, 1H), to 7.61-EUR 7.57(m, 1H), 6.89 in(d, J=2.4 Hz, 3H), the 6.06(t, J=2.4 Hz, 1H), of 3.77(s, 3H), 3,61(s, 6H); 19F NMR(282 MHz, DMSO-d6): -61,85, -163,20; LC/MS: purity: 97%; MS(mass/charge): 439(MH+).+
333N2,N4-Bis(3-methoxy-5-triptoreline)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,80(users, 1H), 9,72(s, 1H), 8,25(d, J=3.3 Hz, 1H), to 7.77-7,72(m, 1H), 7,60-7,52(m, 3H), 6,92(s, 1H), 6.75 in(s, 1H), of 3.77(s, 3H), 3,71(s, 3H); 19F NMR(282 MHz, DMSO-d6): -61,90, -161,82; LC/MS: purity: 97%; MS(mass/charge): 477(MH+).+
3345-fluoro-N4-(3-methoxy-5-triptoreline)-N2-(3-methyl-5-triptoreline)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,83(users, 1H), 9,72(users, 1H), 8,25(d, J=3.6 Hz, 1H), 7,81-to 7.68(m, 3H), EUR 7.57-7,52(m, 1H), 7,06(s, 1H), of 6.96-6,91(m, 1H, in), 3.75(s, 3H), and 2.26(s, 3H); 19F NMR(282 MHz, DMSO-d6): -61,82, -162,02; LC/MS: purity: 91%; MS(mass/charge): 461(MH+).+
3355-fluoro-N4-(3-methoxy-5-triptoreline)-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,67(users, 1H), 9,24(users, 1H), 8,17(d, J=3.6 Hz, 1H), 7,84 for 7.78(m, 1H), to 7.59(s, 1H), 6,95-6,87(m, 3H), 3,74(s, 3H)and 3.59(s, 6H); 19F NMR(282 MHz, DMSO-d6): -61,86, -163,40; LC/MS: purity: 96%; MS(the mass/charge): 469(MH+).+
336N2-(3-Chloro-4-hydroxy-5-were)-5-fluoro-N4-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.56(s, 1H), which is 9.09(s, 1H), 8,61(s, 1H), 8,14(d, J=3.6 Hz, 1H), 7,82-to 7.77(m, 1H), EUR 7.57-7,53(m, 1H), 7,52-of 7.48(m, 1H), 7,27-of 7.23(m, 1H), 6.89 in(users, 1H), 3,76(s, 3H), 2,10(s, 3H); 19F NMR(282 MHz, DMSO-d6): -61,80, -164,13; LC/MS: purity: 96%; MS(mass/charge): 444(MH+).+
337N2-(3,5-Dichloro enyl)-5-fluoro-N4-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,74(s, 1H), to 9.70(s, 1H), 8,25(d, J=3.6 Hz, 1H), to 7.77-7,71(m, 3H), 7,55 is 7.50(m, 1H), 7.03 is-7,01(m, 1H), 6,95-6,93(m, 1H), 3,79(s, 3H); 19F NMR(282 MHz, DMSO-d6): -61,78, -161,76; LC/MS: purity: 96%; MS(mass/charge): 448(MH+).+
338N2-[3,5-Bis(hydroxymethyl)phenyl]-5-fluoro-N4-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,11(users, 1H), 9,82(users, 1H), compared to 8.26(d, J=4,2 Hz, 1H), 7,83-7,79(m, 1H), EUR 7.57-7,51(m, 1H), 7,34(users, 2H), 6,99-6,94(m, 2H), to 4.38(s, 4H), 3,74(s, 3H); LC/MS: purity: 92%; MS(mass/charge): 439(MH+).++
339N2-(4-Chloro-3, 5dimethylphenyl)-5-fluoro-N4-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,98(users, 1H), 9,66(users, 1H), 8,24(d, J=4,2 Hz, 1H), 7,76-7,71(m, 1H), 7,56-7,52(m, 1H), 7,37(s, 2H), 6,98-to 6.95(m, 1H, in), 3.75(s, 3H), of 2.20(s, 6H); LC/MS: purity: 98%; MS(mass/charge): 442(MH+).-
340N2,N4-Bis(3,5-acid)-5-fluoro-2,4-pyrimidinediamine++
341N2,N4-Bis(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,11(s, 1H), 8,98(s, 1H), with 8.05(d, 1H, J=3,9 Hz), 7,33(users, 2H), 7,24(userd, 2H), 6,69(users, 1H), 6,51(users, 1H), 2,25(users, 6H), and 2.14(s, 6H); LC/MS: purity: 100%; MS(mass/charge): 336(M+).+
342N2-[3,5-Bis(hydroxymethyl)phenyl]-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,10(s, 1H), which is 9.09(s, 1H), 8,02(d, 1H, J=3,9 Hz), 7,44(s, 2H), 7,28(d, 1H, J=3.0 Hz), 7,24(d, 1H, J=2.7 Hz), 6,86(s, 1H), 6,79(d, 1H, J=8.7 Hz), of 5.05(t, 2H, J=6 Hz), 4,39(d, 4H, J=5.4 Hz), 4,22(users, 4H); LC/MS: purity: 97%; MS(mass/charge): 399(MH+).+
343N2-[3,5-Bis(hydroxymethyl)phenyl]-N4-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,19(s, 1H), 9.15, with(s, 1H), 8,08(d, 1H, J=3.6 Hz), 7,46(s, 2H), 7,01(d, 2H, J=2.1 Hz), 6,86(s, 1H), 6,21(t, 1H, J=1.8 Hz), to 5.03(t, 2H, J=5.4 Hz), to 4.38(d, 4H, J=5.4 Hz), 3,68(, 6H); LC/MS: purity: 86%; MS(mass/charge): 401(MH+).++
344N2-[3,5-Bis(hydroxymethyl)phenyl]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,55(s,1H), 9,27(userd, 1H), 8,97(s, 1H), 8,04(d, 1H, 3.6 Hz), 7,44(d, 2H, J=1.2 Hz), 7,39(DD, 1H, J=2.4 and 8.4 Hz), 7,24(d, 1H, J=2.4 Hz), to 6.88(d, 1H, J=8.7 Hz), 6,85(users, 1H), 6,38(, 2H), 5,08(t, 1H, J=5.6 Hz), is 4.93(t, 1H, J=5.7 Hz), to 4.38 (d, 2H, J=5.4 Hz), or 4.31 (d, 2H, J=6 Hz), 1,41 (C, 6N); LC/MS: purity: 93%; MS(mass/charge): 440(MH+).+
345N2-[3,5-Bis(hydroxymethyl)phenyl]-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,26(s,1H), 9.15, with(s, 1H), 8,07(userd, 1H, J=3,9 Hz), 7,79(DD, 1H, J=2.7 and 9 Hz), 7,74(d, 1H, J=2.7 Hz), the 7.43(s, 2H), 7,11(d, 1H, J=9 Hz), 6,86(s, 1H), 5,06(t, 2H, J=5.4 Hz), to 4.38(d, 4H, J=5.4 Hz), of 3.84(s, 3H); LC/MS: purity: 98%; MS(mass/charge): 405(MH+).+
346N2-[3,5-Bis(hydroxymethyl)phenyl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,50(users, 1H), 9.28 are(s, 1H), 8,16(d, 1H, J=3.6 Hz), with 8.05(d, 1H, J=2.7 Hz), to 7.93(DD, 1H, J=2.7 and 9.0 Hz), 7,52(d, 1H, J=8.7 Hz), 7,44(s, 2H), 6.87 in(s, 1H), 5,09(t, 2H, J=5.7 Hz), to 4.41(d, 4H), J=5.4 Hz); LC/MS: purity: 97%; MS(mass/charge): 409(M+).+
347N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-N2-[1-(N-methylaminomethyl)indol-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,02(s, 1H), 10,49(s, 1H), RS 9.69(d, 1H, J=4,8 Hz), at 9.53(s, 1H), 8,12(d, 1H, J=3.6 Hz), 7,52(d, 1H, J=8,4 Hz), 7,38(t, 1H, J=2.7 Hz), 7,11(s, 1H), for 6.81(d, 1H, J=2.4 Hz), 6,72(DD, 1H, J=1.8 and an 8.4 Hz), 6,59(DD, 1H, J=2.4 and 8.7 Hz), of 6.49 (s, 1H), of 5.84 (d, 1H, J=8,4 Hz), is 2.74 (d, 3H, J=4.5 Hz), 1,31 (C, 6N); LC/MS: purity: 96%; MS(mass/charge): 476(MH+).+
348N2-(1-Aminocarbonyl-6-yl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d br11.01(s, 1H), 10,44(s, 1H), 9,50(s, 1H), 8,16(d, 1H, J=3.6 Hz), 8,07(d, 1H, J=5.4 Hz), 7,52(d, 1H, J=8,4 Hz), 7,38(t, 1H, J=2.7 Hz), 6.73 x(DD, 1H, J=1.5 and 8.4 Hz), is 6.54(m, 2H), 5,69(d, 1H, J=8.7 Hz), with 2.93(s, 2H), 1,29(6H); LC/MS: purity: 95%; MS(mass/charge): 462(MH+)-
349N2-(4-Chloro-3, 5dimethylphenyl)-N4-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,26(users, 1H), 9,20(s, 1H), 8,10(d, 1H, J=3,9 Hz), of 7.48(s, 2H), 6,94(d, 2H, J=2.4 Hz), 6,23(t, 1H, J=2.4 Hz), 3,68(s, 6H), of 2.20(s, 6H); LC/MS: purity: 92%; MS(mass/charge): 403(MH+).+
350N4-(3,5-Acid)-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,20(s, 1H), 9,05(s, 1H), 8,08(d, 1H, J=3.6 Hz), 7,27(s, 2H), 6,97(d, 2H, J=2.1 Hz), 6,51(s, 1H), 6,21(t, 1H, J=1.8 Hz), to 3.67(s, 6H), of 2.15(s, 6H); LC/MS:purity: 96%; MS(mass/charge): 369(MH+).++-
351N4-(3,5-Acid)-N2-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,16(s, 1H), 9,96(s, 1H), with 8.05(d, 1H, J=3.3 Hz), 7,22(d, 1H, J=2.7 Hz), 7,06(DD, 1H, J=2.4 and 8.7 Hz), of 6.99(d, 2H, J=2.1 Hz), of 6.65(d, 1H, J=8.7 Hz), of 6.20(t, 1H, J=2.1 Hz), 4,17(, 4H), of 3.69(s, 6H); LC/MS: purity: 91%; MS(by weight of the a/charge): 399(MH+). +
352N2-(3,5-Dichlorophenyl)-N4-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,82(users, 1H), 9,58(users, 1H), 8,21(d, 1H, J=3.6 Hz), 7,75(users, 2H),? 7.04 baby mortality(t, 1H, J=1.8 Hz), 6.89 in(d, 2H, J=1,8 Hz), 6,27(t, 1H, J=2.1 Hz), to 3.67(s, 6H); LC/MS: purity: 95%; MS(mass/charge): 410(MH+).+
353N4-(3,5-Acid)-5-fluoro-N2-(3-methyl-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d for 9.47(s, 1H), 9,31(s, 1H), 8,15(d, 1H, J=3.6 Hz), 7,86(s, 1H), 7,79(s, 1H), 6,98(m, 3H), 6,23(t, 1H, J=2.4 Hz), 3,68(s, 6H), and 2.27(s, 3H); LC/MS: purity: 96%; MS(mass/charge): 423(MH+).+
354N2-(3,5-Dichlorophenyl)-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.56(s, 1H), 9.28 are(s, 1H), 8,11(d, 1H, J=3.6 Hz), 7,76(d, 2H, J=1,8 Hz), 7,18(d, 1H, J=2.4 Hz), 7,13(DD, 1H, J=3.6 and 9 Hz), 6,98(t, 1H, J=1.8 Hz), PC 6.82(d, 1H, J=8.7 Hz), 4,21(users, 4H); LC/MS: purity: 81%; MS(mass/charge): 407 (MH+). +
355N4-(3,5-Acid)-5-fluoro-N2-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d at 9.53(s, 1H), was 9.33(d, 1H, J=1.5 Hz), 8,16(d, 1H, J=3.6 Hz), the 7.65(d, 1H, J=2.1 Hz), 6,98(d, 2H, J=2.1 Hz), 6,72(users, 1H), from 6.22(t, 1H, J=2.4 Hz), and 3.72(s, 3H), of 3.69(s, 6H); LC/MS: purity: 96%; MS(mass/charge): 439(MH+).+
356N4-(3,4-Atlanticcity)-5-fluoro-N2-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d for 9.47(s, 1H), 9,23(s, 1H), of 8.09(d, 1H, J=3,9 Hz), to 7.67(s, 1H), to 7.59(s, 1H), 7,27(d, 1H, J=2.7 Hz), 7,18(DD, 1H, J=2.4 and 8.4 Hz), 6,78(d, 1H, J=8.7 Hz), 6,78(s, 1H), 4,21, USS, 4H), and 3.72(s, 3H); LC/MS: purity: 90%; MS(mass/charge) 473(MH+).+
357N2-(3,5-Acid)-5-fluoro-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d for 9.64(s, 1H), 9,29(s, 1H), 8,15(m, 2H), 7.62mm(DD, 1H, J=2.4 and 9 Hz), 7,39(d, 1H, J=8.7 Hz), 6.90 to(d, 2H, J=2.4 Hz), 6,09(t, 1H, J=1.8 Hz), 3,66(s, 6H); LC/MS: purity: 97%; MS(mass/charge: 471(MH+) ++
358N2-(4-Chloro-3, 5dimethylphenyl)-5-fluoro-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,90(users, 1H), 9,56(users, 1H), 8,21(userd, 1H, J=3.6 Hz), 8,06(users, 1H), EUR 7.57(DD, 1H, J=2.4 and 9.0 Hz), the 7.43(d, 1H, J=9.3 Hz), 7,39(s, 2H), 7,06(users, 1H), 25(s, 6H); LC/MS: purity: 97%; MS(the mass/charge): 473(MH+).-
359N2-[3,5-Bis(hydroxymethyl)phenyl]-5-fluoro-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 9.60(s, 1H), to 9.32(s, 1H), 8,16(d, 2H, J=3.6 Hz), of 7.70(DD, 1H, J=2.7 and 9 Hz), 7,47(s, 2H), 7,40(d, 1H, J=9.0 Hz), 6,88(users, 1H), 5,11(t, 2H, J=5.4 Hz), 4,42(d, 4H, J=5.4 Hz); LC/MS: purity: 98%; MS(mass/charge): 471(MH+).+
360N2-(3,5-Dichlorophenyl)-5-fluoro-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,76(s, 1H), 9,72(s, 1H), of 8.25(d, 1H, J=3.6 Hz), 8,00(d, 1H, J=2.4 Hz), 7,74(d, 2H, J=1,8 Hz), 7,58(DD, 1H, J=2.4 and 9.0 Hz), 7,44(d, 1H,J=9.0 Hz), ? 7.04 baby mortality(t, 1H, J=1.8 Hz); LC/MS: purity: 98%; MS(mass/charge): 480(MH+).-
3615-fluoro-N2-(3-methoxy-5-triptoreline)-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,72(s, 1H), for 9.64(s, 1H), 8,23(d, 1H, J=3.6 Hz), 8,07(d, 1H, J=2.4 Hz), to 7.67(users, 1H), 7,60(DD, 1H, J=2.4 and 9.3 Hz), 7,54(users, 1H), 7,39(d, 1H, J=9 Hz), 6.75 in(users, 1H, in), 3.75(s, 3H); LC/MS: purity: 97%: MS(mass/charge): 509(MH+)+
362N2-(3, 5dimethylphenyl)-5-fluoro-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 9.60(s, 1H), 9,19(s, 1H), 8,15(d, 1H, J=3.6 Hz), to 8.12(d, 1H, J=2.4 Hz), 7,60(DD, 2.4 and 8.7 Hz), 7,40(d, 1H, J=9 Hz), 7,22(s, 2H), 6,56(s, 1H), 2,18(s, 6H); LC/MS: purity: 100%; MS(mass/charge): 439(MH+).+-
363N4-(3,4-Atlanticcity)-5-fluoro-N2-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d at 9.53(s, 1H), 9,27(s, 1H), 8,08(d, 1H, J=3.6 Hz), to 7.93(d, 1H, J=4 Hz), 7,37(DD, 1H, J=2.4 and 9.3 Hz), 7,26(d, 1H, J=9 Hz), 7,11(DD, 1H, J=2.4 and 8.7 Hz), to 6.80(d, 1H, J=8,4 Hz), 4,22(s, 4H); LC/MS: purity: 96%; MS(mass/charge): 469(MH+).+
364N4-(3,5-Acid)-5-fluoro-N2-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,59(s, 1H), 9,37(d, 1H, J=0.9 Hz), 8,14(d, 1H, J=2.4 Hz), 7,38(DD, 1H, J=2.7 and 9.3 Hz), 7,27(d, 1H, J=9.0 Hz), 6,91(d, 2H, J=2.4 Hz), of 6.26(t, 1H, J=2.4 Hz), of 3.69(s, 6H); LC/MS: purity: 96%; MS(mass/charge): 471(MH+).+
3655-fluoro-N2-[2-(N-methylamino)carbanilide-7-yl]-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,59(s, 1H), to 9.66(s, 1H), 9,34(s, 1H), 8,46(d, 1H, J=4,8 Hz), to 8.20(d, 1H, J=3.6 Hz), 8,10(d, 1H, J=2.4 Hz), to $ 7.91(d, 1H, J=7,2 Hz), 7,60(DD, 1H, J=2.7 and 9 Hz), 7,39(d, 1H, J=9.0 Hz), 7,24(d, 1H, J=7.5 Hz), 7,06(d, 1H, J=1.8 Hz), 6,94 (t, 1H, J=7.8 Hz), 2,80 (d, 3H, J=4,8 Hz); LC/MS: purity: 100%; MS(mass/charge): 507(MH+).+
3665-fluoro-N2-(3-methyl-5-trifluoromethyl)-N4-[3,4-(ritratto is Ethylenedioxy)phenyl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d to 9.70(s, 1H), 9,60(s, 1H), they were 8.22(d, 1H, J=2.4 Hz), 8,07(d, 1H, J=2.4 Hz), 7,87(s, 1H), of 7.70(s, 1H), 7,60(DD, 1H, J=2.1 and 9 Hz), 7,41(d, 1H, J=9 Hz),? 7.04 baby mortality(s, 1H), 2,31(s, 3H); LC/MS: purity: 100%; MS(mass/charge): 493(MH+).+
367N2-(3,4-Atlanticcity)-5-fluoro-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,48(s, 1H), 9,12(s, 1H), 8,11(d, 2H, J=3.6 Hz), to 7.59(DD, 1H, J=2.4 and 9 Hz), 7,39(d, 1H, J=9.3 Hz), 7,22(d, 1H, J=2.4 Hz), of 6.99(DD, 1H, J=2.4 and 8.7 Hz), 6,70(d, 1H, J=9 Hz); LC/MS: purity: 96%; MS(mass/charge): 469(MH+).++
368N4-(3,5-Acid)-5-fluoro-N2-[2-(N-methylamino)carbanilide-7-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,70(s, 1H), 9,31(s, 1H), 9.28 are(s, 1H), 8,43(d, 1H, J=4,8 Hz)to 8.14(d, 1H, J=4,8 Hz), of 8.04(DD, 1H, J=0,9 and 8.4 Hz), 7,19(d, 1H, J=7.5 Hz), 7,03(d, 1H, J=2H, J=2.4 Hz), 6.89 in(t, 1H, J=8,4 Hz), 6,24(t, 1H, J=2.4 Hz), 3,69 (C, 6N), 2,80 (d, 3H, J=4,55 Hz); LC/MS: purity: 91%; MS(mass/charge): 437(MH+).++
369 N2-(3-Chloro-5-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,57(s, 1H), 9,35(s, 1H), 9,27(s, 1H), 8,10(d, 1H, J=3.6 Hz), 7,47(m, 1H), 7,25(DD, 1H, J=2.7 and 8.7 Hz), 7,16(d, 2H, J=2.1 Hz), 6.87 in(d, 1H, J=8,4 Hz), of 6.49(t, 1H, J=1.8 Hz), 3,66(s, 3H), of 1.40(s, 6H); LC/MS: purity: 100%; MS(mass/charge): 445(MH+).+
370N2-(3-Chloro-5-methoxyphenyl)-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,31(s, 1H), of 9.21(s, 1H), 8,08(d, 1H, J=3,9 Hz), of 7.48(t, 1H, J=1.8 Hz), 7,20(m, 3H), to 6.80(d, 1H, J=8,4 Hz), of 6.49(t, 1H, J=2.4 Hz), is 4.21(s, 4H), to 3.67(s, 3H); LC/MS: purity: 95%; MS(mass/charge): 403(MH+).+
3715-fluoro-N4-(3,4-methylenedioxyphenyl)-N2-[2-(N-methylamino)carbanilide-7-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,27(s, 1H), 9,25(s, 2H), 8,43(d, 1H, J=4.5 Hz), of 8.09(d, 1H, J=3,9 Hz), 8,01(d, 1H, J=7.8 Hz), 7,51(d, 1H, J=2.1 Hz), 7,6(m, 2H),? 7.04 baby mortality(d, 1H, J=1.8 Hz), 6,92(t, 1H, J=7,8 Hz), at 6.84(d, 1H, J=8.1 Hz), 6,01(s, 2H), 2,81 (d, 3H, J=4,8 Hz); LC/MS: purity: 100%; MS(mass/charge): 421(MH+).+
372N2-(3,5-Acid)-5-fluoro-N4-(3,4-methylenedioxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,20(s, 1H), 9,10(s, 1H), with 8.05(d, 1H, J=3.6 Hz), 7,44(d, 1H, J=2.1 Hz), 7,16(DD, 1H, J=2.1 and 8.4 Hz), 6,93(d, 2H, J=2.4 Hz), at 6.84(d, 1H, J=8,4 Hz), 6,04(t, 1H, J=2.1 Hz), 5,99(, 2H), to 3.64(s, 6H); LC/MS: purity: 89%; MS(mass/charge): 385(MH+).+
3735-fluoro-N4-(3,4-methylenedioxyphenyl)-N2-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,49(s, 1H), of 9.30(s, 1H), 8,10(d, 1H, J=3.6 Hz), 9,67(users, 1H), 7,58(users, 1H), 7,40(d, 1H, J=1.8 Hz), 7,11(DD, 1H, J=1.8 and an 8.4 Hz), at 6.84(d, 1H, J=8,4 Hz), 6,70(users, 1H), 6,99(s, 2H), to 3.73(s, 3H); LC/MS: purity: 97%; MS(mass/charge): 423(MH+).+
3745-fluoro-N4-(3,4-methylenedioxyphenyl)-N2-(3-methyl-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,46(s, 1H), 9,29(s, 1H), 8,10(d, 1H, J=3.6 Hz), 7,78(users, 1H), 7,39(d, 1H, J=2.1 Hz), 7,10(1H, J=2.4 and 8.4 Hz), 6,99(users, 1H), 6,85(d, 1H, J=8,4 Hz), of 5.99(s, 2H), 2,28(s, 3H); LC/MS: purity: 99%; MS(mass/charge): 407(MH+).-
375N2-(3,5-Dichlorophenyl)-5-fluoro-N4-(3,4-methylenedioxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,59(s, 1H), 9,36(s, 1H), 8,12(d, 1H, J=3,9 Hz), 7,74(d, 2H, J=2.1 Hz), 7,30(d, 1H, J=2.1 Hz), 7,06(DD, 1H, J=2.4 and 8.4 Hz), 6,97(t, 1H, 2.1 Hz), to 6.88(d, 1H, J=8,4 Hz); 6,00(s, 2H,); LC/MS: purity: 94%; MS(mass/charge): 393(M+).+
376N2-(3, 5dimethylphenyl)-5-fluoro-N4-(3,4-methylenedioxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,18(users, 1H), 9,03(s, 1H), 8,04(d, 1H, J=3,9 Hz), the 7.43(d, 1H, J=2.1 Hz), 7,24(s, 2H), 7,11(DD, 1H, J=2.1 and 8.4 Hz), 6,85(d, 1H, J=8,4 Hz), 6,50(users, 1H), 5,98(s, 2H), 2,16(s, 6H); LC/MS: purity: 87%; MS(mass/charge): 353(MH+).+
377N2-(4-Chloro-2,5-acid)-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 100%; MS(mass/charge): 439(M+).+
378 N2-(3-Chloro-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR(DMSO-d6): d as 10.63(s, 1H), of 10.05(s, 1H), 9,62(s, 1H), 8,15(d, 1H, J=4,8 Hz), 7,66(users, 1H), 7,44(DD, 2H, J=1.8 and 8.7 Hz), 7,35(userd, 1H, J=9 Hz), 7,20(DD, 1H, J=2.1 and 8.7 Hz), 7,10(userd, 2H, J=7.5 Hz), 7,02(d, 1H, J=9 Hz), 6.89 in(d, 1H, J=8,4 Hz), of 3.78 (s, 3H), of 2.28 (s, 3H), 1.39 in (C, 6N); LC/MS: purity: 97%; MS(mass/charge): 444(M for parentally molecule +H).+
379N2-(4-Chloro-2,5-acid)-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,24(s, 1H), with 8.05(d, 1H, J=3,9 Hz), 7,87(s, 1H), of 7.70(s, 1H), 7,17(d, 1H, J=2.4 Hz), 7,06(m, 2H), 6,74(d, 1H, J=8.7 Hz), is 4.21(s, 4H), 3,79(s, 3H), of 3.54(s, 3H); LC/MS: purity: 100%; MS(mass/charge): 433(MH+).+
380N2-(4-Chloro-2,5-acid)-N4-(3,5-acid)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 100%; MS(mass/charge): 435(MH+).+
381N4-(3,5-Acid)-5-fluoro-N2-(2-methoxycarbonylmethyl-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,36(s, 1H), of 8.25(d, 1H, J=1.8 Hz), 8,11(d, 1H, J=3,9 Hz), EUR 7.57(m, 3H), of 6.99(m, 2H), of 6.26(t, 1H, J=2.1 Hz), 3,88(s, 3H), of 3.69(s, 6H); LC/MS: purity: 92%; MS(mass/charge): 439(MH+).++
382N2-(2-Carboxybenzene-5-yl)-N4-(3,5-acid)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 91%; MS(mass/charge): 425(MH+).--
383N2-(2-Carboxybenzoyl-7-yl)-N4-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,85(s, 1H), 9,31(s, 1H), 9,26(s, 1H), 8,16(d, 1H, J=3.6 Hz), to 8.12(d, 1H, J=8.1 Hz), 7,22(d, 1H, J=8.1 Hz), 7,02(d, 2H, J=2.1 Hz), 6,91(t, 1H, J=7.8 Hz), and 6.25(s, 1H), 3,70(users, 6H); LC/MS: purity: 80%; MS: 424(MH+)+
384N4-(3,5-Acid)-5-fluoro-N2-[2-(N-2-hydroxyethyl-N-methylamino)carbanilide-7-yl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d to 11.52(s, 1H), of 9.30(users, 1H), 9,27(s, 1H), 8,14(d, 1H, J=3.6 Hz), of 8.04(m, 1H), 7,22(d, 1H, J=8,4 Hz), 7,03(m, 2H), 6.90 to 9M, 2H), 6,23 (USS, 1H), 3,68(s, 6H), 3,64(users, 4H), 3,20(s, 3H); LC/MS: purity: 94%; MS(mass/charge): 481(MH+).+++
385N4-(3,4-Atlanticcity)-5-fluoro-N4-methyl-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR(CDCl3): d 7.50 for(users, 1H), 7,30(m, 2H), 6,91(userd, 1H, J=7,2 Hz), 6.73 x(m, 5H), of 4.49(s, 2H), or 4.31(s, 4H), of 3.60(s, 3H), of 2.92(d, 3H, J=4.5 Hz); LC/MS: purity: 97%, MS(mass/charge):440(MH+)++-
386N4-(3,4-Atlanticcity)-N2-(3,5-acid)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(CDCl3): d 7,94(d, 1H, J=5,1 Hz), 7,50(userd, 1H), 6.90 to(d, 1H, J=9 Hz), 6,83(s, 1H), 6.73 x(m, 3H), 6,62(d. 1H, 2.4 Hz), or 4.31(m, 4H), of 3.80(s, 3H), 3,79(s, 3H), of 3.60(s, 3H); LC/MS: purity: 90%, MS: 413(MH+).++-
387N2-(3, 5dimethylphenyl)-N4-(3,4-atlanticcity)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1 NMR(CDCl3): d 7.50 for(userd, 1H), 7,40(s, 1H), 7,27(m, 1H), 6.90 to(userid, 1H), for 6.81(m, 1H), 6,77(d, 2H, J=2.4 Hz), 6,70(DD, 1H, J=2.7 and 8.7 Hz), 4,30(s, 4H), 3,50(s, 3H), 2,32(s, 6H); LC/MS: purity: 94%; MS(mass/charge): 381(MH+).+-
388N2-(3,5-Acid)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d or 10.60(s, 1H), of 9.21(s, 1H), 7,94(d, 1H, J=6.0 Hz), 7,01(d, 2H, J=1.2 Hz), to 6.88(m, 2H), 6.75 in(d, 1H, J=2.4 Hz), equal to 6.05(t, 1H, J=2.4 Hz), 3,60(s, 6H), to 3.41(s, 3H), of 1.34(s, 6H); LC/MS: purity: 92%, MS(mass/charge): 454(MH+).--
389N4-(3,5-Acid)-N2-[2-(N-1,1-dimethyl-2-hydroxyethylamine)carbanilide-7-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,63(s, 1H), 9,25(d, 1H, J=7.8 Hz), 8,14(d, 1H, J=3.6 Hz), 8,02(d, 1H, J=8.1 Hz), 7,53(s, 1H), 7,19(d, 1H, J=7.5 Hz), 7,14(s, 1H),? 7.04 baby mortality(s, 2H), 6.89 in(t, 1H, J=7.5 Hz), 6,23(, 1H), 4,94(t, 1H, J=6.3 Hz), of 3.69(s, 6H), 3,53 (d, 2H, J=5.4 Hz), 1,33 (C, 6N); LC/MS: purity: 80%; MS(mass/charge): 495(MH+).+-
3902-Chloro-N4-(3,4-atlanticcity)-5-the top-N4-methyl-4-pyrimidinamine 1H NMR(CDCl3): d a 7.85(d, 1H, J=4,8 Hz)6,86(d, 1H, J=8,4 Hz), 6.73 x(d, 1H, J=2.7 Hz), 6,60(DD, 1H, J=2.7 and 8.1 Hz); LC/MS: purity: 100%, MS(mass/charge):296(M+).---
391N2-(3, 5dimethylphenyl)-5-fluoro-N4-methyl-N4-(3-oxo-2,2,4-trimethylpent[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(CDCl3): d of 7.95(d, 1H, J=6.4 Hz), to 7.67(users, 1H), 7,21(s, 2H), of 6.96(s, 1H), 6.87 in(DD, 1H, J=2.4 and 8.7 Hz), 6,78(d, 1H, J=2.4 Hz), 6,72(s, 1H), 3,55(s, 3H), of 3.32(s, 3H), of 2.30(s, 6H), of 1.53(s, 6H); LC/MS: purity: 92%, MS(mass/charge): 436(MH+).++
392N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-methyl-N4-(3-oxo-2,2,4-trimethylpent[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(CD3OD): d to 7.77(d, 1H, J=2.4 Hz), 7,75(userd, 1H), 7,34(DD, 1H, J=2.7 and 9.3 Hz), 7,05(d, 1H, J=1.8 Hz), to 6.95(m, 3H), 4,62(s, 3H), 3,83(s, 3H), 3,51(s, 3H), of 1.48(s, 6H); LC/MS: purity: 94%; MS(mass/charge): 472(M+).++
393N2-(3,5-Acid)-5-fluoro-N4-methyl-N4-(3-oxo-2,2,4-trimethylpent[1,4]oxazin-6-yl)-2,4-pyrimidinediamine++
394N2-(3-Chloro-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N4-methyl-2,4-pyrimidinediamineLC/MS: purity: 93%, MS(mass/charge): 351(MH+).++
395N4-(3,4-Atlanticcity)-5-fluoro-N2-(2-methoxycarbonylmethyl-5-yl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 7.95(s, 1H), 7,76(userd, 1H), 7,54(s, 1H), 7,49(userd, 2H), 6.87 in(d, 1H, J=8,4 Hz), 6,79(DD, 1H, J=2.4 and 6.6 Hz), 6,74(userd, 1H); LC/MS: purity: 94%; MS(mass/charge): 452(MH+).+++
396N2-(3, 5dimethylphenyl)-N4-(3-oxo-2,2,4-trimethylpent[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 90%; MS(mass/charge): 422(MH+).++ +
397N2-(3,5-Acid)-N4-(3-oxo-2,2,4-trimethylpent[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 94%; MS(mass/charge): 454(MH+).+++
398N4-(3,5-Acid)-5-fluoro-N4-methyl-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamineLC/MS: purity: 94%; MS(mass/charge):442(MH+).+-
399N4-(3,5-Acid)-N2-(3, 5dimethylphenyl)-5-fluoro-N4-methyl-2,4-pyrimidinediamineLC/MS: purity: 92%, MS(mass/charge):382(MH+).++-+
400N2,N4-Bis(3,5-acid)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,23(s, 1H), of 7.97(d, 1H, J=5,1 Hz), 7,01(d, 2H, J=1,8 Hz), 6,45(d, 2H, J=1.2 Hz), 6,34(ushort, 1H), 6,05(ushort, 1H), and 3.72(s, 6H), 3,68(6H), of 3.45(s, 3H); LC/MS: purity: 95%, MS(mass/charge):415(MH+). +-
401N4-(3,5-Acid)-5-fluoro-N2-(2-methoxycarbonylmethyl-5-yl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO): d to 9.70(s, 1H), 8,13(s, 1H), 8,04(d, 1H, J=3.8 Hz), 7,69(s, 1H), 7.62mm(m, 2H), 6,51(d, 2H, J=1.5 Hz), 6,44(ushort, 1H); 3,88(s, 3H), and 3.72(s, 6H), of 3.46(s, 3H); LC/MS: MS(mass/charge): 453(MH+), purity: 95%.++
402N4-[3-Chloro-4-(methoxycarbonyl-1,1-dimethylmethylene)phenyl]-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 81%; MS(mass/charge): 459(MH+)+
403N2-(3, 5dimethylphenyl)-N4-[4-(methoxycarbonyl-1,1-dimethylmethylene)phenyl]-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 80%; MS(mass/charge): 425(MH+).+
404N2-(3-Chloro-4-methoxyphenyl)-N4-(3,5-acid)-5-fluoro-N4-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 10,00(s, 1H), 8,08(d, 1H, J=6,00 Hz), 7,89(d, 1H, J=5,1 Hz), 7,47(DD, 1H, J=2.7 and 9.3 Hz), was 7.08(d, 1H, J=9.0 Hz), 6,53(d, 2H, J=1,8 Hz), 6,46(t, 1H, J=2.1 Hz); LC/MS: purity: 92%, 419(MH+).--
405N2-(4-Chloro-3-methoxyphenyl)-N4-(3,5-acid)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.30(s, 1H), 9,03(s, 1H), 8,07(d, 1H, J=4, 2 Hz), of 7.48(d, 1H, J=2.1 Hz), 7,37(DD, 1H, J=2.4 and 8.4 Hz), 7,24(s, 2H); LC/MS: purity: 91%; MS(mass/charge): 419(M+).+-
406N4-(3,5-Acid)-5-fluoro-N4-methyl-N2-[2-(N-methylamino)carbanilide-7-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,71(s, 1H), 9,39(s, 1H), 8,44(userd, 1H, J=4,8 Hz), 8,02(m, 2H), 7,20(d, 1H, J=7.5 Hz),? 7.04 baby mortality(d, 1H, J=2.1 Hz), 6,93(t, 1H, J=7.8 Hz), 6,47(d, 2H, J=2.1 Hz), 6,41(t, 1H, J=2.1 Hz), and 3.72(s, 6H), of 3.46(s, 3H), of 2.81(d, 3H, J=4.5 Hz); LC/MS: purity: 95%; MS(mass/charge): 450(M+).+-
4072-Chloro-N4-[3-chloro-4-(etoxycarbonyl-1,1-dimethylmethylene)phenyl]-5-fluoro-4-pyrimidinamine 1H NMR(DMSO-d6): d 8,07(d, 1H, J=2.7 Hz), 7,69(m, 1H), 7,45(m, 1H), 6,95(d, 1H, J=9 Hz), 6,92(users, 1H), 4,28(square, 2H, J=6.9 Hz), of 1.62(s, 6H), is 1.31(t, 3H, J=7.2 Hz); LC/MS: purity: 85%; MS(mass/charge): 388(M+).+
408N4-[3-Chloro-4-(etoxycarbonyl-1,1-dimethylmethylene)phenyl]-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(CD3OD): d to $ 7.91(d, 1H, J=3.6 Hz), 7,74(d, 1H, J=2.7 Hz), 7,66(DD, 1H, J=2.7 and 8.7 Hz), 6,91(d, 1H, J=9 Hz), 6,78 (d, 2H, J=2.1 Hz), 6,12(t, 1H, J=2.1 Hz), 4.26 deaths(square, 2H, J=6.9 Hz), 3,71(s, 6H), of 1.59(s, 6H), of 1.29(t, 3H, J=7.2 Hz); LC/MS: purity: 90%; MS(mass/charge): 505(MH+).+
409N4-[3-Chloro-4-(hydroxycarbonyl-1,1-dimethylmethylene)phenyl]-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 13,15(users, 1H), 9,38(s, 1H), 9,18(s, 1H), 8,10(d, 1H, J=3,9 Hz), to 7.93(s, 1H), to 7.84(DD, 1H, J=2.7 and 9.3 Hz), to 7.77(d, 1H, J=2.7 Hz), 6,91(m, 3H), 6,07(t, 1H, J=2.1 Hz), the 3.65(s, 6H), of 1.52(s, 6H); LC/MS: purity: 90%; MS(mass/charge): 477(MH+).++-
410N4-[3-Chloro-4-(ethoxycarbonyl who -1,1-dimethylmethylene)phenyl]-N2-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,36(s, 1H), 9,17(s, 1H), 8,08(d, 1H, J=3.6 Hz), 7,78(d, 1H, J=2.7 Hz), of 7.75(d, 1H, J=2.1 Hz), of 7.70(DD, 1H, J=3.0 and 9.3 Hz), 7,44(DD, 1H, J=2.7 and 9.0 Hz), of 6.99(d, 1H, J=9.0 Hz), 6,88(d, 1H, J=9.0 Hz), 4,20(q, 2H, J=7,2 Hz), of 3.78 (s, 3H), of 1.52 (s, 6N), of 1.20 (t, 3H, J=6.9 Hz); LC/MS: purity: 93%; MS(mass/charge): 509(M+).+++
411N4-(3,4-Atlanticcity)-5-fluoro-N4-methyl-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamineLC/MS: purity: 91%; MS(mass/charge): 420(MH+).++-
412N4-(3,4-Atlanticcity)-5-fluoro-N4-methyl-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d being 9.61(s, 1H), to 8.57(s, 1H), 8,17(s, 1H), becomes 9.97(d, 1H, J=6.0 Hz), 7,70(userd, 1H, J=4,8 Hz), 7,52(userd, 1H, J=7.8 Hz), 7,38(d, 1H, J=8.1 Hz), 7,33(s, 1H), 6,79(m, 3H), 4,24(s, 4H), 3,44(s, 3H); LC/MS: purity: 92%, MS(mass/charge): 420(MH+).++
413N4-(3,4-Acid)-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d and 9.1(s, 1H), 8,97(s, 1H), 8,02(d, 1H, J=3,9 Hz), 7,24(m, 4H), to 6.88(d, 1H, J=J=8,4 Hz), 6.48 in(d, 1H), of 3.73(s, 3H), of 3.65(s, 3H), 2,12(s, 6H); LC/MS: purity: 97%, MS(mass/charge): 369(MH+).++-
414N2-(3,5-Acid)-N4-(3,4-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,17(s, 1H), 9,05(s, 1H), 8,03(d, 1H, J=3,9 Hz), 7,32(DD, 2.4 and 8.7 Hz), 7,24(d, 1H, J=2.4 Hz), 6,92(d, 2H, J=2.4 Hz), 6,85(d, 1H, 8,4 Hz), 6,03(t, 1H, J=2.1 Hz), to 3.73(s, 3H), 3,66(s, 3H), of 3.60(s, 6H); LC/MS: purity: 96%; MS(mass/charge): 401(MH+).++-
415N4-(3,4-Acid)-N2-[2-(etoxycarbonyl)indol-7-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,89(s, 1H), 9,25(s, 1H), of 9.21(s, 1H), 8,10(d, 1H, J=3,9 Hz), 8,87(s, 1H), 8,73(m, 3H), 7,11(d, 1H, J=2.1 Hz), to 6.88(m, 2H), 4,32(square, 2H, J=3,9 Hz), 3,76(s, 3H), 3,66(s, 3H), 1,34(sq, t, 3H, J=3,9 Hz); LC/MS: purity: 93%, MS(mass/charge): 452(M+).++-
416N4-(3,4-Atlanticcity)-5-fluoro-N4-methyl-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(VHI is-d6): d 9,59(s, 1H), with 8.05(s, 1H), of 7.96(d, 1H), J=5.7 Hz), 7,80(users, 4H), 7,27(s, 1H), 6,85(m, 2H), 6,78(DD, 1H), to 4.52(s, 4H), to 3.41(s, 3H), and 3.31(s, 3H); LC/MS: purity: 91%; MS(mass/charge): 420(MH+).+-
4172-Chloro-N4-(3,4-acid)-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(DMSO-d6): d of 8.09(d, 1H, J=5.4 Hz), 7,02(d, 1H, J=2.4 Hz), 6,93(d, 1H, J=8,4 Hz), at 6.84(DD, 1H, J=2.1 and 8.4 Hz in), 3.75(s, 3H), 3,71(s, 3H); LC/MS: purity: 87%; MS(mass/charge):298(M+).----
4182-Chloro-N4-(3,4-atlanticcity)-5-fluoro-N4-(methoxycarbonylmethyl)-4-pyrimidinamineLC/MS: purity: 99%, MS(mass/charge): 354(M+).--
419N4-(3,4-Acid)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,29(s, 1H), of 9.21(s, 1H), with 8.33(s, 1H), 8,07(d, 1H, J=3.0 Hz), of 8.04(s, 1H), to 7.61(userd, 1H), 7,39(s, 1H), 7,29(userid, 1H, J=2.7 and 8.4 Hz), 7,25(m, 3H), 6,76(d, 1H, J=8.7 Hz), 3,70(s, 3H), of 3.64(s, 3H); LC/MS: purity: 98%, MS(mass/charge): 408(MH+).+ +-
420N4-(3,4-Atlanticcity)-5-fluoro-N2-(indol-6-yl)-N4-(methoxycarbonylmethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,77(s, 1H), 9,05(s, 1H), 7,94(d, 1H, J=5.7 Hz), of 7.70(s, 1H), 7,32(d, 1H, J=2,8 Hz), 7,19(d, 1H, J=1.5 Hz), 7,17(t, 1H, J=3 Hz), PC 6.82(m, 3H), 6,28(d, 1H, J=2.1 Hz), 4,60(, 2H), 4,24(s, 4H), to 3.33(s, 3H); LC/MS: purity: 99%; MS(mass/charge): 450(MH+).+-
421N4-(3,4-Acid)-5-fluoro-N2-[2-(N-methylaminomethyl)indol-7-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,66(s, 1H), 9,27(s, 1H), which 9.22(s, 1H), to 8.41(userd, 1H, J=4,8 Hz), of 8.09(d, 1H, J=3.3 Hz), to 7.99(d, 1H, J=7.8 Hz), 7,33(DD, 1H, J=2.4 and 8.4 Hz), 7,28(d, 1H, J=2.7 Hz), 7,18(d, 1H, J=7.5 Hz), 7,03(d, 1H, J=2.1 Hz), 6.89 in(m, 2H), of 3.75 (s, 3H), 3,66 (s, 3H), 2,80 (d, 3H, J=4,2 Hz); LC/MS: purity: 91%; MS(mass/charge): 437(MH+).+-
422N4-(3,4-Acid)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,36(s, 1H), 9,24(s, 1H), with 8.33(s, 1H), 8,07(d, 1H, J=3,9 Hz), of 7.75(d, 2H, J=6.0 Hz), 7,50(d, 2H, J=8.7 Hz), of 7.75(d, 2H, J=8.7 Hz), 7,47(s, 1H), 7,26(m, 2H), 6,92(d, 1H, J=96 Hz), 3,76(s, 3H), of 3.69(s, 3H); LC/MS: purity: 94%; MS(mass/charge): 408(M+).++-
423N4-(3,4-Acid)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,36(s, 1H), which 9.22(s, 1H), 8,29(s, 1H), 8,12(s, 1H), 8,08(d, 1H, J=3 Hz), 7,81(DD, 1H, J=1.8 and a 7.1 Hz), 7,49(d, 1H, J=6.9 Hz), 7,31(m, 4H), 6,79(d, 1H, J=8.7 Hz), 3,71(s, 3H), to 3.67(s, 3H); LC/MS: purity: 98%, MS(mass/charge): 409 (MH+).++-+
424N4-(3,4-Acid)-5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6):d 9,50(s, 1H), 9.28 are(s, 1H), 8,09(d, 2H, J=4.5 Hz), 7,76(m, 4H), 7,28(m, 3H), 6,93(d, 1H, J=8,4 Hz), 3,76(s, 3H), 3,70(s, 3H); LC/MS: purity: 89%; MS(mass/charge): 408(M+).+-
425N2-(3-Chloro-4-methoxyphenyl)-N4-(3,4-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,17(s, 1H), remaining 9.08(s, 1H), 8,02(d, 1H, J=3,9 Hz), to 7.84(s, 1H, J=2.7 Hz), 7,41(DD, 1H, J=3.0 and 9.3 Hz), 7,27(DD, 1H, J=2.4 and 8.7 Hz), 7,21(d, 1H, J=2.4 Hz), 6,97 (d 1H, J=8.7 Hz), 6,88(d, 1H, J=8.7 Hz), of 3.77(s, H), to 3.73 (s, 3H), 3,68 (s, 3H); LC/MS: purity: 95%; MS(mass/charge): 405(M+).++-
426N2-[3-(4-Acetylpiperidine)phenyl]-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,13(s, 1H), 8,99(s, 1H), 8,02(d, 1H, J=4, 2 Hz), 7,22(m, 4H), 7,03(m, 1H), 6,77(d, 1H, J=8.7 Hz), 6,50(userd, 1H, J=7,2 Hz), 4,21(users, 4H), to 3.02(osirm, 2H), 2.95 and(osirm, 2H), 2,02(s, 3H); LC/MS: purity: 97%, MS(mass/charge):465(MH+).++-
427N2-[4-(4-Acetylpiperidine)phenyl]-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,07(s, 1H), of 8.92(s, 1H), 7,98(d, 1H, J=3,9 Hz), of 7.48(d, J=8.7 Hz), 7,33(d, 1H, J=2.4 Hz), 7,18(DD, 1H, J=2.1 and 8.7 Hz), 6,83(d, 1H, J=9.3 Hz), 6.73 x(d, 1H, J=1H, J=8.7 Hz), 4,23(users, 4H), 3,56(users, 4H), 3,03(t, 2H, J=5,1 Hz), of 2.97 (t, 2H, J=5,1 Hz), 2,03 (s, 3H); LC/MS: purity: 96%; MS(mass/charge): 465(MH+).++-
428N2-[3-(4-Acetylpiperidine)phenyl]-N4-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 23(s, 1H), 9,07(s, 1H), of 8.09(d, 1H, J=3 Hz), 7,26(s, 1H), 7,15(d, 1H, J=Hz), 7,07(t, 1H, J=8,4 Hz), 6,97(d, 2H, J=2.4 Hz), 6,50(userd, 1H, J=7.5 Hz), 6,18(d, 1H, J=2.1 Hz), 5,74(s, 1H), 3,49(m, 4H), of 3.32(s, 6H), 2,96(m, 4H), for 2.01 (s, 3H); LC/MS: purity: 98%; MS(mass/charge): 467(M+).+-
429N2-[3-(4-Acetylpiperidine)phenyl]-N4-(3,4-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,17(users, 1H), 8,99(s, 1H), 8,02(d, 1H, J=3,9 Hz), 7,27(m, 2H), 7,01(userd, 1H, J=8,4 Hz), 7,00(t, 1H, J=8,1 Hz)6,86(d, 1H, J=8,4 Hz), 6.48 in(userd, 1H, J=9.9 Hz), 6,13(users, 1H), 3.72 points with, 3H), 3,62(s, 3H), 3.46 in(m, 4H), 2,96(m, 2H), 2,90 (m, 2H), 2,02 (s, 3H); MS(mass/charge): 467(M+); purity: 99%.+-
430N2-[4-(4-Acetylpiperidine)phenyl]-N4-(3,4-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,11(s, 1H), 8,88(s, 1H), 7,98(d, 1H, J=3,9 Hz), 7,46(d, 2H, J=9,3 Hz), 7,27(m, 2H), 6.87 in(d, 1H, J=8,4 Hz), to 6.80(d, 2H, J=9 Hz), 3,74(s, 3H), of 3.65(s, 3H), of 3.56(m, 4H), 3,02(m, 2H), 2,96(m, 2H), 2,03(s, 3H); LC/MS: purity 90%, MS(mass/charge): 467(M+).+-
431N2-[3-(Acetylpiperidine)phenyl]-5-fluoro-N4-(3,4-(tetrafluorothiophenol)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,62(s, 1H), 9,19(s, 1H), 8,14(m, 1H), 7.62mm(DD, 1H, J=2.7 and 9.6 Hz), 7,39(d, 1H, J=9 Hz), 7.23 percent(d, 1H, J=8 Hz), 7,16(s, 1H), 7,07(t, 1H, J=2.6 Hz), 6,55(d, 1H, J=2.6 Hz), 6,12(s, 1H), 3,54(users, 4H), 2,02(s, 3H); LC/MS: purity: 91%; MS(mass/charge): 537(MH+).++-
432N2-[4-(4-Acetylpiperidine)phenyl]-5-fluoro-N4-(3,4-(tetrafluorothiophenol)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.57(s, 1H), 9,11(s, 1H), 8,15(userd, 1H), 8,10(d, 1H, J=3.3 Hz), EUR 7.57(userid, 1H, J=9.6 Hz), was 7.45(d, 2H, J=8.7 Hz), 7,37(d, 1H, J=9 Hz), 6.87 in(d, 2H, J=9,3 Hz), 6,69(d, 1H, J=8.7 Hz), 6,47(d, 1H, J=8.7 Hz), 3,52(m, 4H), 2,99 (m, 2H), 2,85 (m, 2H), 2,03 (s, 3H), LC/MS: purity: 88%; MS(mass/charge): 537(MH+).+-
433N4-(3,4-Acid)-N2-(3, 5dimethylphenyl)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,05(s, 1H), 7,89(d, 1H, J=6.0 Hz), 7,31(s, 2H), 6,93(d, 1H, J=2.7 Hz), 6.90 to(s, 1H), for 6.81(DD, 1H, J=2.4 and 8.1 Hz), 6,50(s, 1H, in), 3.75(s, 3H), 3,71(s, 1H), 3,42(s, 3H), 2,18(s, 6H); LC/MS: purity: 95%, MS(mass/charge): 383(MH+).+-
434 N2-(3,5-Acid)-N4-(3,4-acid)-5-fluoro-N4-methyl-2,4-pyrimidinediamineLC/MS: purity: 96%, MS(mass/charge): 415(MH+).+-
435N4-(3,4-Acid)-N2-[2-(etoxycarbonyl)indol-7-yl]-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,94(s, 1H), to 9.32(s, 1H), 8,15(d, 1H, J=J=7.5 Hz), of 7.97(d, 1H, J=6.0 Hz), 7,22(d, 1H, J=7.8 Hz), 7,12(d, 1H, J=2.1 Hz), of 6.96(m, 3H), PC 6.82(m, 1H), 4,33(square, 2H, J=4, 2 Hz), 3,76(s, 3H), and 3.72(s, 3H), 3.46 in(s, 3H), of 1.35(t, 3H, J=6.9 Hz); LC/MS: purity: 90%; MS(mass/charge): 466(MH+).+-
436N4-(3,4-Acid)-5-fluoro-N2-(indol-6-yl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,85(s, 1H), 9,07(s, 1H), 8,03(s, 1H), 7,87(d, 1H, J=8,4 Hz), 7,34(d, 1H, J=8.7 Hz), 7,16(m, 2H), 6,93(m, 2H), 6.90 to(s, 1H), 6,80(m, 1H), 6,28(s, 1H, in), 3.75(s, 3H), of 3.73(s, 3H), 3,44(s, 3H); LC/MS: purity: 94%; MS(mass/charge): 394 (MH+).+-
437N2-[4-(4-Acetylpiperidine)phenyl]-N4-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine+-
438N4-(3,4-Acid)-5-fluoro-N4-methyl-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,42(s, 1H), 8,40(s, 1H), 8,28(users, 1H), to 7.93(d, 1H, J=8.7 Hz), 7,58(userd, 1H, J=6,8 Hz), 7,55(s, 1H), 7,27(m, 2H), of 6.96(d, 1H, J=2.4 Hz), 6,92(m, 1H), for 6.81(DD, 1H, J=2.1 and 8.4 Hz), of 3.75(s, 3H), 3,75 2(s, 3H), 3,47(s, 3H); LC/MS: purity: 80%; MS(mass/charge): 422(MH+).++-
439N4-(3,4-Acid)-5-fluoro-N4-methyl-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,50(s, 1H), to 8.62(d, 1H, J=3.6 Hz), 8,17(s, 1H), 7,94(d, 1H, J=6.0 Hz), of 7.70(DD, 1H, J=2.4 Hz), 7,33(m, 2H), 6,97(d, 1H, J=2.4 Hz), 6,92(d, 1H, J=8,4 Hz), PC 6.82(DD, 1H, J=2.4 and to 8.7 Hz), 3,76(s, 3H), of 3.73(s, 3H), of 3.48 (s, 3H); LC/MS: purity: 80%; MS(mass/charge): 422(MH+).++--
440N4-(3,4-Acid)-5-fluoro-N4-methyl-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,59(s, 1H), 8,10(s, 1H), 7,98(m, 2H), 7.62mm(DD, 1H, J=2.1 and is of 6.6 Hz), 7,27(s, 1H), of 6.96(m, 2H), 6,92(s, 1H), for 6.81(DD, of 2.4 and 8.4 Hz), is 6.61(DD, 1H, J=2.1 and 6.6 Hz), 5,67(users, 1H), of 3.77(s, 3H), and 3.72(s, 3H), of 3.45(s, 3H).+-
441N2-(3, 5dimethylphenyl)-N4-(3,4-atlanticcity)-5-fluoro-N4-(methoxycarbonylmethyl)-2,4-pyrimidinediamineLC/MS: purity: 91%, MS 9m/e): 439(MH+).+-
442N2-(3,5-Acid)-N4-(3,4-atlanticcity)-5-fluoro-N4-(methoxycarbonylmethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,14(s, 1H), of 7.97(d, 1H, J=5.7 Hz), at 6.84(m, 5H), 6,07(m, 1H), to 4.62(s, 2H), 4,24(s, 3H), 3,68(users, 4H), to 3.34(s, 6H); LC/MS: purity: 94%, MS: 471(MH+).+-
443N4-(3,4-Atlanticcity)-5-fluoro-N4-(methoxycarbonylmethyl)-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,40(s, 1H), 8,40(s, 1H), 8,00(d, 1H, J=J=4,2 Hz), 7,93(users, 1H), 7,60(m, 1H), EUR 7.57(s, 1H), 7,27(m, 2H), 6,83(m, 3H), 4,63(s, 2H), 4,23(s, 4H), 3,51(s, 3H); LC/MS: purity: 95%, MS(mass/charge): 478(MH+).+ -
444N4-(3,4-Atlanticcity)-5-fluoro-N4-(methoxycarbonylmethyl)-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,49(s, 1H), 8,24(s, 1H), 8,17(s, 1H), 8,00(d, 1H, J=5.7 Hz), 7,76(userd, 1H, J=9.6 Hz), 7,51(userd, 1H, J=8.1 Hz), 7,34(m, 2H), 6,86(m, 1H), 6,83(m, 1H), with 4.64(s, 2H), 4,24(s, 4H), of 3.54(s, 3H); LC/MS: purity: 91%; MS(mass/charge): 478(MH+).+-
445N4-(3,4-Atlanticcity)-5-fluoro-N4-(methoxycarbonylmethyl)-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d being 9.61(s, 1H), 8,10(s, 1H), with 8.05(d, 1H, J=8.1 Hz), to 7.77(DD, 2H, J=8,4 Hz), of 7.70(DD, 2H, J=8,4 Hz), 7,29(s, 1H), 6,85(m, 3H), with 4.64(s, 2H), 4,25(s, 4H), 3,63(s, 3H); LC/MS: purity: 92%, MS(mass/charge): 478(MH+).+-
446N4-(3,4-Atlanticcity)-5-fluoro-N4-(methoxycarbonylmethyl)-N2-[3-(N-methylamine)carbonintensity]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,24(s, 1H), of 7.97(d, 1H, J=5.7 Hz), 7,94(m, 1H), 7,22(m, 2H), was 7.08(t, 1H, J=7.8 Hz), 6,83(m, 3H), of 6.49(m, 1H), to 4.62(s, 2H), 4,39(s, 2H), 4,24(s, 4H), of 3.60(s, 3H), 2,66(d, 3H, J=51 Hz); LC/MS: purity: 97%, MS(498(MH+).+-
447N4-(3,4-Acid)-5-fluoro-N4-methyl-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,24(s, 1H), 7,94(users, 1H), of 7.90(d, 1H, J=5.7 Hz), 7,46(t, 1H, J=2.1 Hz), 7,27(userd, 1H, J=9 Hz), 7,10(t, 1H, J=5,1 Hz), 6,93(m, 1H), 6,79(DD, 1H, J=2.7 and 8.7 Hz), 6,45(DD, 1H, J=the 1.8 and 8.1 Hz), 6,12(m, 1H), to 4.38(s, 2H), of 3.75 (s, 3H), and 3.72 (s, 3H), 3,42 (s, 3H), 2,4 (userd, 3H); LC/MS: purity: 98%; MS(mass/charge): 442(MH+).+-
448N2-[4-Chloro-3-(N-methylamino)carbonitril]-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,37(s, 1H), 9,18(s, 1H), 8,21(d, 1H, J=4.5 Hz), with 8.05(d, 1H, J=3.6 Hz), 7,72(m, 2H), 7,22(m, 2H), 7,20(m, 3H), 6,80(userid, 1H, J=2.1 and 9 Hz), 4,11(users, 4H), 2,71(d, 3H, J=4.5 Hz); LC/MS: purity: 95%; MS(mass/charge): 430(MH+).++-
449N2-[4-Chloro-3-(N-methylamino)carbonitril]-N4-(3,4-acid)-5-fluoro-2,4-pyrimidinediamine1H NM is(DMSO-d6): d to 8.20(d, 1H), with 8.05(d, 1H, J=3,9 Hz), of 7.75(d, 1H, J=2.7 Hz), 7,66(DD, 1H, J=3.0 and 8.7 Hz), 7,32(DD, 1H, J=2.4 and 9.0 Hz), 7.23 percent(s, 1H), 7,18(m, 1H), to 6.88(d, 1H, J=8.7 Hz), of 4.00(s, 4H), 3,76(s, 3H), 3,71(s, 3H), 2,69(d, 3H, J=3.6 Hz); LC/MS: purity: 95%; MS(mass/charge): 432(M+).+-
450N2-[4-Chloro-3-(N-methylamino)carbonitril]-N4-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 8.15(d, 1H, J=4, 2 Hz), 7,82(DD, 1H, J=2.7 and 9.0 Hz), to 7.61(d, 1H, J=2.7 Hz), 7,25(d, 1H, J=9.0 Hz), of 6.96(t, 2H, J=2.4 Hz), of 6.26(t, 1H, J=2.1 Hz), 3,71(s, 6H), 2,71(d, 3H, 3,3 Hz); LC/MS: purity: 87%; MS(mass/charge): 432(M+).+-
451N4-(3-Chloro-4-methoxyphenyl)-N2-[4-chloro-3-(N-methylamino)carbonitril]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d is 8.16(d, 1H, J=3,9 Hz), of 7.70(d, 1H, J=2.7 Hz), to 7.64(m, 2H), 7,30(d, 1H, J=9.3 Hz), 7,10(d, 1H, J=9 Hz), a 3.87(s, 3H), 2,69(s, 3H); LC/MS: purity: 91%; MS(mass/charge): 536(M+).++
452N4-[3-Chloro-4-(etoxycarbonyl-1,1-dimethylmethylene)phenyl]-N2-[4-chloro-3-(N-methylamino)carbonifer-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,65(users, 2H), compared to 8.26(d, 1H, J=4,8 Hz), 8,17(s, 1H), 7,80-7,58(m, 4H), 7,27(d, 1H, J=8.7 Hz), 6.89 in(d, 1H, J=9 Hz), 4,20(square, 2H, J=6.9 Hz), 2,71(d, 3H, J=4, 2 Hz), and 1.54(s, 6H), 1,21(t, 3H, J=7.2 Hz); LC/MS: purity: 91%; MS(mass/charge): 536(M+).++
453N2-[4-Chloro-3-(N-methylamino)carbonitril]-N4-(3,4-atlanticcity)-5-fluoro-N4-methyl-4-pyrimidinediamine1H NMR(DMSO-d6): d RS 9.69(s, 1H), 8,28(d, 1H, J=4.5 Hz), 7,98(d, 1H, J=6.0 Hz), 7,83(d, 1H, J=2.4 Hz), 7,66(DD, 1H, J=2.7 and 8.7 Hz), 7,29(d, 1H, J=9 Hz), at 6.84(m, 2H), 6,76(DD, 1H, 2.7 and 8.7 Hz), 4,24(, 4H), to 3.38(s, 1H), 2,72(d, 3H, J=4,2 Hz); LC/MS: purity: 91%; MS(mass/charge): 444(M+).+-
454N2-[4-Chloro-3-(N-methylamino)carbonitril]-N4-(3,4-acid)-5-fluoro-N4-methyl-4-pyrimidinediamine1H NMR(DMSO-d6): d 9,50(s, 1H), compared to 8.26(d, 1H, J=4.5 Hz), to 7.93(d, 1H, 6,0 Hz), 7,87(d, 1H, J=2.7 Hz), to 7.68(DD, 1H, J=2.4 and 5.7 Hz), 7,26(d, 1H, J=8.7 Hz), 6,93(m, 2H), 6,80(DD, 1H, J=2.4 and 8.4 Hz), 3,76(, 3H), 3,76(s, 3H), and 3.72(s, 3H), 3,41 (s, 3H), 2,71 (d, 3H, J=4.5 Hz); LC/MS: purity: 90%; MS(mass/charge): 446(M+).+-
N2-[4-Chloro-3-(N-methylamino)carbonitril]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,71(s, 1H), 9,87(s, 1H), compared to 8.26(d, 1H, J=4, 2 Hz), 8,16(d, 1H, J=4, 2 Hz), 7,63(m, 2H), 7,25(m, 2H), 7,17(d, 1H, J=2.1 Hz), 6.90 to(d, 1H, J=8.7 Hz), 2,71(d, 3H, J=4.5 Hz), 1,40(, 6H); LC/MS: purity: 97%, MS(mass/charge): 471(M+).++-
456N2-[3-Chloro-4-(N-methylamino)carbonitril]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 10.74(s, 1H), 10,34(s, 1H), to 10.09(s, 1H), 8,24(d, 1H, J=4,8 Hz), 8,15(d, 1H, J=4.5 Hz), 7,83(d, 1H, J=1.5 Hz), 7,44(DD, 1H, J=1.8 and an 8.4 Hz), 7.23 percent(m, 2H), 6,93(d, 1H, J=8,4 Hz), 2,71(d, 3H, J=4,2 Hz)of 1.40(s, 6H); LC/MS: purity: 94%; MS(mass/charge): 471(M+).+++
457N2-(2,6-Dimethoxyphenyl-3-yl)-N4-(3,5-acid)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 8,02(d, 1H, J=8,4 Hz), 7,87(d, 1H, J=6.4 Hz), 7,76(s, 1H), 6,41(m, 3H), 6,32(d, 1H, J=J=8,4 Hz)to 3.89(s, 3H), 3,82(s, 3H), 3,71(s, 3H), 3,34(s, 3H); LC/MS: purity: 95%, MS(the mass/charge): 416(MH+).++ +
458N2-(2,6-Dimethoxyphenyl-3-yl)-N4-(3,4-atlanticcity)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6); d 8,02(d, 1H, J=8,4 Hz), 7,82(d, 1H, J=6.6 Hz), 7,68(s, 1H), 6,79(m, 2H), 6,72(DD, 1H, J=2.1 and 8.1 Hz), 6.30-in(d, 1H, J=8,1 Hz)to 4.23(s, 4H), to 3.89(s, 3H), 3,81(s, 3H), of 3.28(s, 3H); LC/MS: purity: 97%, MS(mass/charge): 414(MH+).--
459N4-(3,5-Acid)-N2-(2,6-dimethoxyphenyl-3-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,12(s, 1H), of 7.97(d, 1H, J=5,1 Hz), 7,89(s, 1H), 7,82(d, 1H, J=7.8 Hz), to 6.95(s, 1H), 6,28(d, 1H, J=7.8 Hz), x 6.15(s, 1H), 3,84(s, 3H), 3,83(s, 3H), 23,64(s, 6H); LC/MS: purity: 85%, MS(mass/charge): 402(MH+).+-
460N2-(2,6-Dimethoxyphenyl-3-yl)-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 93%, MS(mass/charge): 400(MH+).+-
461N4-(3,4-Atlanticcity)-5-fluoro-N2-mate the-N4-methyl-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 7,72(d, 1H, J=5,1 Hz), 6,79(d, 1H, J=9.0 Hz), 6.73 x(users, 1H), 6,66(userd, 1H), 2,74(d, 3H, J=4.5 Hz); LC/MS: purity: 93%, MS(mass/charge): 291(MH+).--
462N2-Dimethyl-N4-(3,4-atlanticcity)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d for 7.78(d, 1H, J=6.0 Hz), to 6.80(d, 1H, J=8,4 Hz), 6.75 in(d, 1H, J=2.7 Hz), of 6.66(DD, 1H, J=1.8 and an 8.4 Hz), 4,22(s, 4H), and 3.31(s, 3H), 3,30(s, 3H); LC/MS: purity: 95%; MS(mass/charge): 305(MH+).--
463N2-[3-Chloro-4-(N-methylamino)carbonitril]-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.45(s, 1H), 9,24(s, 1H), 8,11(m, 2H), 7,89(d, 1H, J=2.1 Hz), 7,54(DD, 2.1 and 8.7 Hz), 7,20(m, 3H), PC 6.82(d, 1H, J=8,4 Hz), 4,22(users, 4H), 2,71(d, 3H, J=4.5 Hz); LC/MS: purity: 99%, MS(mass/charge): 430(MH+).++-
464N2-[3-Chloro-4-(N-methylamino)carbonitril]-N4-(3,4-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,34(s, 1H), 10,10(s,1H), of 8.25(d, 1H, J=4.5 Hz), 8,18(d, 1H, J=4,8 Hz), 7,81(s, 1H), 7,41(d, 1H, J=8.1 Hz), 7,27(d, 1H, J=8,4 Hz), 7,18(m, 2H), 6,95(d, 1H, J=8.7 Hz in), 3.75(s, 3H), 3,68(s, 3H), 2,71(d, 3H); LC/MS: purity: 96%; MS(mass/charge): 432(MH+).+-
465N2-[3-Chloro-4-(N-methylamino)carbonitril]-N4-(3,5-acid)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 100%, MS(mass/charge): 432(MH+).+-
466N4-(3-Chloro-4-methoxyphenyl)-N2-[3-chloro-4-(N-methylamino)carbonitril]-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 100%, MS(mass/charge): 436(MH+).++-
467N4-[3-Chloro-4-(etoxycarbonyl-1,1-dimethylmethylene)phenyl]-N2-[3-chloro-4-(N-methylamino)carbonitril]-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 95%, MS(mass/charge): 536(MH+).+++
468 N2-[3-Chloro-4-(N-methylamino)carbonitril]-5-fluoro-N4-(3-hydroxyphenyl)-2,4-pyrimidinediamineLC/MS: purity: 100%, MS(mass/charge): 388(MH+).++-
469N4-(3,4-Atlanticcity)-5-fluoro-N2-(2-hydroxyethyl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 7.70(d, 1H, J=5.7 Hz), 6,79(d, 1H, J=8.7 Hz), 6,74(d, 1H, J=2.4 Hz), of 6.66(DD, 1H, J=2.4 and 8.4 Hz), 6,50(t, 1H, J=5,1 Hz), br4.61(t, 1H, J=5.4 Hz), 4,22(s, 4H), 3,47(square, 2H, J=6.3 Hz), 3,29(t, 2H, J=5.4 Hz)at 3.25(s, 3H); LC/MS: purity: 96%; MS(mass/charge): 321(MH+).--
4702-Chloro-N4-[3-chloro-4-(etoxycarbonyl-1,1-dimethylmethylene)phenyl]-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(CDCl3): d 7,87(d, 1H, J=7.8 Hz), 7,25(m, 1H), 6,95(m, 2H), 4,25(square, 2H, J=4,8 Hz), 3.46 in(s, 3H), of 1.65(s, 6H), of 1.29(t, 3H, J=4,8 Hz); LC/MS: purity: 95%, MS(mass/charge): 404(MH+; Cl37).-+
471N4-(3,4-Atlanticcity)-5-fluoro-N2-isopropyl-N4-methyl-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d of 7.70(d, 1H, J=5.7 Hz), 6,77(d, 1H, J=8.7 Hz), 6,37(d, 1H, J=2.4 Hz), of 6.68(DD, 1H, J=2.4 and 8.7 Hz), 6,44(d, 1H, J=8.1 Hz), 4,22(s, 4H), 3,90(Sept, 1H, J=7.5 Hz), with 3.27(s, 3H), 1,12(d, 6H, J=6.6 Hz); LC/MS: purity: 93%; MS(mass/charge): 319(MH+).C--
472N2-(2,6-Dimethoxyphenyl-3-yl)-5-fluoro-N4-(3-hydroxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d accounted for 10.39(s, 1H), 9,52(s, 1H), to 8.20(d, 1H, J=5.7 Hz), to 7.77(m, 1H), was 7.08(m, 1H), 6,59(m, 1H), 6,45(d, 1H, J=8,4 Hz), 6,37(d, 1H, J=8.1 Hz), 3,88(s, 3H), 3,86(s, 3H); LC/MS: purity: 89%, MS(mass/charge): 358(MH+).+-
473N2-[3-Chloro-4-(N-methylamino)carbonitril]-N4-(3,4-atlanticcity)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,71(s, 1H), 8,16(d, 1H, J=4.5 Hz), 8,00(d, 1H, J=5.7 Hz), 7,95(d, 1H, J=1.8 Hz) 7,53(DD, 1H, J=2.1 and 8.4 Hz), 7,29(d, 1H, J=8,4 Hz), 6,85(m, 2H), 6,77(DD, 1H, J=2.1 and 8.4 Hz), 4,24(s, 4H), 3,40(s, 3H), 2,71(d, 3H, J=3,9 Hz); LC/MS: purity: 100%; MS(mass/charge): 444(M+).+-
474N2-[3-Chloro-4-(N-methylamino)to bonisteel]-N4-(3,4-acid)-5-fluoro-N4-methyl-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,86(users, 1H), 8,18(d, 1H, J=4.5 Hz), 8,03(DD, 1H, J=1,2 and 6.3 Hz), 7,94(d, 1H, J=1.8 Hz), 7,52(DD, 1H, J=2.1 and 8.4 Hz), 7,30(d, 1H, J=8,4 Hz), of 6.99(d, 1H, J=2.4 Hz), 6,93(d, 1H, J=and 8.4 Hz), 6,86(DD, 1H, J=2.4 and 8.4 Hz), 3,76 (s, 3H), and 3.72 (s, 3H), of 3.45 (s, 3H), 2,71 (d, 3H, J=4.5 Hz); LC/MS: purity: 100%; MS(mass/charge): 446(M+).+-
475N4-[4-Chloro-3-(N-methylamino)carbonitril]-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,11(s, 1H), 9,83(s, 1H), 8.30 to(d, 1H, J=4.5 Hz), 8,24(d, 1H, J=4.5 Hz), 8,00(DD, 1H, J=2.7 and 8.7 Hz), 7,63(d, 1H, J=2.4 Hz), was 7.36(d, 1H, J=8.7 Hz), 6,78(d, 2H, J=2.1 Hz), 6,20(t, 1H, J=2.1 Hz), to 3.67(s, 6H), 2,73(d, 3H, J=5.4 Hz); LC/MS: purity: 100%; MS(mass/charge): 432(M+).++-
476N4-[4-Chloro-3-(N-methylamino)carbonitril]-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.91(s, 1H), 9,52(s, 1H), 8,29(d, 1H, J=4,8 Hz), 8,19(d, 1H, J=4, 2 Hz), 8,00(userid, 1H, J=8.7 Hz), a 7.62(d, 1H, J=2.1 Hz), 7,38(d, 1H, J=9.0 Hz), 7,17(s, 2H), 6,63(s, 1H), 2,72(d, 3H, J=4,8 Hz), 2,19(s, 6H); LC/MS: purity: 95%; MS(mass/charge): 400(M+).++-
477N4-[4-Chloro-3-(N-methylamino)carbonitril]-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.55(s, 1H), to 9.32(s, 1H), 8,31(userd, 1H), 8,15(users, 1H), 7,99(m, 2H), 7,79(m, 1H), 7,39(d, 1H, J=9 Hz), 7,29(m, 2H), 7,14(m, 1H), of 6.49(userd, 1H, J=7.8 Hz), 4,36(s, 2H), 2,72(s, 3H), of 2.64(s, 3H); LC/MS: purity: 99%, MS(mass/charge): 459 (MH+).++-
478N2-[3-Chloro-4-(N-methylamino)carbonitril]-N4-[4-chloro-3-(N-methylamino)carbonitril]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d RS 9.69(s, 1H), 8.34 per(d, 1H, J=4.5 Hz), by 8.22(d, 1H, J=3.6 Hz), 8,17(d, 1H, J=4.5 Hz), 7,95(DD, 1H, J=2.7 and 8.7 Hz), 7,81(d, 1H, J=2.1 Hz), 7,71(d, 1H, J=2.7 Hz), 7,56(DD, 1H, J=2.1 and and 8.4 Hz), the 7.43(d, 1H, J=9.0 Hz), 7,30 (d, 1H, J=8,4 Hz), 2,73 (d, 6N, J=4.5 Hz); LC/MS: purity: 100%; MS(mass/charge): 466(M+).+-
479N4-[4-Chloro-3-(N-methylamino)carbonitril]-N2-(indol-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,98(s, 1H), 10,28(s, 1H), of 10.05(s, 1H), 8,35(d, 1H, J=4, 2 Hz), 8,21(d, 1H, J=4,8 Hz), 7,86(userd, 1H, J=8.7 Hz), to 7.77(d, 1H, J=2.7 Hz), 7,54(s, 1H), 7,47(d, 1H, J=8,4 Hz), 7,35(d, 1H, J=8.7 Hz), 7,30(m,1H), 7,05(DD, 1H, J=1.8 and an 8.4 Hz), 6,38 (users, 1H), 2,75 (d, 3H, J=4.5 Hz), LC/MS: purity: 92%; MS(mass/charge): 411(M+).+-
480N4-(3,4-Atlanticcity)-5-fluoro-2-methoxy-N4-methyl-4-pyrimidinamineLC/MS: purity: 97%, MS(mass/charge): 292(M+).--
481N4-[3-Chloro-4-(N-methylamino)carbonitril]-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,85(users, 1H), 9,50(users, 1H), they were 8.22(m, 2H), 7,89(m, 2H), 7,33(d, 1H, J=9.0 Hz), 6,85(d, 2H, J=1.5 Hz), 6,13(d, 1H, J=1.8 Hz), 3,66(s, 1H), 2,74(d, 3H, J=4.5 Hz); LC/MS: purity: 98%, MS(mass/charge): 432(M+).++-
482N4-[3-Chloro-4-(N-methylamino)carbonitril]-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.01(s, 1H), 9,65(s, 1H), 8,24(d, 1H, J=4.5 Hz), 7,85(users, 1H), 7,35(d, 1H, J=8.7 Hz), 7,16(s, 2H), 6,94(s, 2H), 6,65(s, 1H), 2,74(d, 3H, J=4,8 Hz)to 2.29(s, 3H), of 2.20(s, 3H); LC/MS: purity: 98%, MS(mass/charge): 400(M+).+ +-
483N4-[3-Chloro-4-(N-methylamino)carbonitril]-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,82(users, 1H), 9,56(users, 1H), they were 8.22(m, 2H), 7,98(userd, 1H), to $ 7.91(d, 1H, J=1.5 Hz), 7,82(userd, 1H, J=8.7 Hz), 7,37(d, 1H, J=8.7 Hz), 7,22(m, 3H), 6,56(m, 1H), to 4.38(s, 2H), 2,74(d, 3H, J=4.5 Hz), of 2.64(d, 3H, J=4,8 Hz); LC/MS: purity: 97%; MS(mass/charge): 459(M+).+
484N2-[4-Chloro-3-(N-methylamino)carbonitril]-N4-[3-chloro-4-(N-methylamino)carbonitril]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d RS 9.69(s, 1H), 9,60(s, 1H), 8,25(m, 3H), a 7.85(m, 3H), of 7.36(m, 3H), of 2.75(d, 3H, J 4.8 Hz), 2,70(d, 3H, J=4.5 Hz); LC/MS: purity: 86%), MS(mass/charge): 463(M+).-
485N4-[3-Chloro-4-(N-methylamino)carbonitril]-5-fluoro-N2-(indol-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,99(s, 1H), 10,10(s, 1H), 9,80(users, 1H), of 8.25(d, 1H, J=4.5 Hz), to 8.20(d, 1H, J=4, 2 Hz), to 7.93(d, 1H, J=1.8 Hz), 7,83(userd, 1H, J=9.6 Hz), 7,58(s, 1H), 7,47(m, 2H), 7,30(m, 2H), 7,12(userd, 1H, J=8.1 Hz), 6,38(s, 1H); LC/MS: estate: 86%; MS(mass/charge): 411(M+).++
486N4-(2-Aminopurin-6-yl)-2-chloro-5-fluoro-4-pyrimidinamine1H NMR(CD3OD): d is 8.16(d, 1H, J=3.6 Hz), 7,46(m, 2H), 6,32(DD, 1H, J=3.9 and 5.1 Hz); LC/MS: purity: 92%, MS(mass/charge): 240(M+).--
487N4-(3,4-Atlanticcity)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(CD3OD): d the 7.43(d, 1H, J=7,2 Hz), 6,83(d, 1H, J=8,4 Hz), 6,78(d, 1H, J=2.4 Hz), 6,72(DD, 1H, J=2.7 and 8.4 Hz), 4,25(s, 4H), 3,40(s, 3H); LC/MS: purity: 100%, MS(mass/charge): 278(MH+).--
4882-Chloro-N4-(3,5-acid)-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(CD3OD): d to 7.93(d, 1H, J=5.4 Hz), 6,46(s, 3H,), to 4.62(s, 6H), of 3.77(s, 3H); LC/MS: purity: 100%, MS(mass/charge): 298(MH+).+-
489N2-(2-Ethoxycarbonylmethyl-7-yl)-5-fluoro-N4-(2-Ki is axetil)-2,4-pyrimidinediamine 1H NMR(CD3OD): d 7,73(m, 2H), 7,34(DD, 1H, J=1.2 and 8.1 Hz), 7,17(s, 1H),? 7.04 baby mortality(t, 2H, J=7.8 Hz), to 4.38(square, 2H, J=6.9 Hz), of 3.69(t, 2H, J=5,1 Hz)to 3.58(t, 2H, J=6.6 Hz), of 1.42(t, 3H, J=7.2 Hz); LC/MS: purity: 98%; MS(mass/charge): 360(MH+).--
4902-Chloro-N4-(2,6-dimethoxyphenyl-5-yl)-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(CD3OD): d 7,89(d, 1H, J=5.7 Hz), EUR 7.57(d, 1H, J=8.1 Hz), 6,37(d, 1H, J=8.7 Hz), of 3.94(s, 3H), 3,91(s, 3H), 3,37(s, 3H); LC/MS: purity: 97%, MS(mass/charge): 299(MH+).--
4912-Chloro-N4-(3,5-dichloro-4-methoxyphenyl)-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(CD3OD): d 8,02(d, 1H, J=5.4 Hz), the 7.43(s, 2H), 3,91(s, 3H), 3,47(s, 3H); LC/MS: purity: 89%; MS(mass/charge): 366(MH+).--
492N2-(Bis-2-hydroxyethyl)-N4-(3,4-atlanticcity)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 7,76(d, 1H, J=4,7 Hz), 6,79(d, 1H, J=6.3 Hz), 6.75 in(d, 1H, J=2.4 Hz), to 6.67(DD, 1H, J=2.7 and 9.3 Hz), 4,71(users, 2H), 4,22(users, 4H), 3,57(users, 4H), 3,31(ush the D.C, 4H), of 3.28(s, 3H); LC/MS: purity: 97%, MS(mass/charge): 416(MH+).--
493N4-(3,4-Atlanticcity)-5-fluoro-N2-[4-(N-methylamino)sulfonyl-3-methoxyphenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,58(s, 1H), 9,29(s, 1H), 8,11(d, 1H, J=3.6 Hz), 7,47(m, 2H), 7,42(userid, 1H), 7,27(d, 1H, J=2.1 Hz), 7,13(DD, 1H, J=2.1 and 8.4 Hz), 6,79(d, 1H, J=8.7 Hz), 6.73 x(m, 1H), 4,22(s, 4H), 3,68(s, 3H), 2,34(d, 3H, J=4,8 Hz); LC/MS: purity: 80%; MS(mass/charge): 462(MH+).++-
494N4-(3,4-Acid)-5-fluoro-N2-[3-methoxyphenyl-4-(N-methylamino)sulfonyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.57(s, 1H), was 9.33(s, 1H), 8,11(d, 1H, J=3.6 Hz), 7,51(d, 1H, J=1.8 Hz), was 7.45(d, 1H, J=8,4 Hz), 7,34(DD, 1H, J=1.8 and 8.7 Hz), 7.24 to(m, 2H), 6.90 to(d, 1H, J=9.0 Hz), 6,72(d, 1H, J=4,8 Hz in), 3.75(s, 3H), to 3.67(s, 3H), 3,63(s, 3H), 2,33 (d, 3H, J=4,8 Hz); LC/MS: purity: 96%; MS(mass/charge): 464(M+).++-
495N4-(3,5-Acid)-5-fluoro-N2-[3-methoxyphenyl-4-(methylamino)sulfonyl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d for 9.64(s, 1H), 9,37(s, 1H), 8,16(userd, 1H), 7,51(m, 3H), 6,97(users, 2H), of 6.71(userd, 1H), 6,24(users, 1H), 3,69(s, 6H), and 3.31(s, 3H), 2,34(d, 3H, J=4,8 Hz); LC/MS: purity: 94%; MS(mass/charge): 464(M+).+-
496N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-methoxyphenyl-4-(methylamino)sulfonyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 10.62(s, 1H), 9,50(s, 1H), 9,43(s, 1H), 8,12(d, 1H, J=3,9 Hz), 7,46(s, 1H), 7,44(s, 1H), 7,26(DD, 1H, J=2.4 and 8.7 Hz), 7,14(d, 1H, J=2.4 Hz), 6.90 to(d, 1H, J=8,4 Hz), 6,70(d, 1H, J=5.4 Hz), of 3.69(s, 3H), 2,32(d, 3H, J=5,1 Hz), 1,41 (C, 6N); LC/MS: purity: 90%; MS(mass/charge): 503(MH+).+++
497N4-(4-Chloro-3-triptoreline)-5-fluoro-N2-[3-methoxyphenyl-4-(methylamino)sulfonyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,88(s, 1H), 9,72(s, 1H), compared to 8.26(m, 2H), 8,18(d, 1H, J=4.5 Hz), the 7.65(d, 1H, J=8.7 Hz), 7,51(d, 1H, J=8.7 Hz), 7,44(m, 2H), 6,74(d, 1H, J=8,4 Hz), and 3.72(s, 3H), 2,34(d, 3H, J=5,1 Hz); LC/MS: purity: 97%, MS(mass/charge): 506(M+).++-
498N4-(3-Chloro-4-three is tomatometer)-5-fluoro-N2-[4-(3-methoxyphenyl-N-methylamino)sulfonyl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,78(s, 1H), 9,72(s, 1H), 8,25(m, 1H), 8,15(d, 1H, J=3.6 Hz), to 7.84(DD, 1H, J=2.4 and 9.0 Hz), 7,52(m, 2H), 7,43(m, 2H), 6,74(m, 1H), 3,74(s, 3H), 2,33(d, 3H, J=2.1 Hz); LC/MS: purity: 83%, MS(mass/charge): 522(M+).++-
4995-fluoro-N4-(3-hydroxyphenyl)-N2-[3-methoxyphenyl-4-(N-methylamino)sulfonyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.57(s, 1H), 9,38(s, 1H), 9,31(s, 1H), 8,13(d, 1H, J=3,9 Hz), 7,51(m, 1H), 7,47(m, 2H), 7,21(d, 1H, J=1.5 Hz), was 7.08(m, 2H), 6,70(d, 1H, J=5.4 Hz), 6,51(userid, 1H, J=8.1 Hz), 3,31(s, 3H), 2,30(d, 3H, J=2,4 Hz); LC/MS: purity: 91%; MS(mass/charge): 420(MH+).++-
500N4-(2,6-Dimethoxyphenyl-3-yl)-N2,N4-dimethyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 7,66(d, 1H, J=5.4 Hz), to 7.59(d, 1H, J=7.5 Hz), 6,54(userd, 1H), 6.35mm(d, 1H, J=8,4 Hz), 3,85(s, 3H), 3,83(s, 3H), 2,71(d, 3H, J=3,9 Hz); LC/MS: purity: 92%, MS(mass/charge): 294(M+).--
501N4-(3,5-Dichloro-4-methoxyphenyl)-N2,N4-dimethyl-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 7,86(d, 1H, J=5.4 Hz), 7,42(s, 2H), 3,80(s, 3H), 3,38(s, 3H), 2,73(d, 3H, J=4,8 Hz); LC/MS: purity: 98%, MS(mass/charge): 331(M+).--
5022-Chloro-5-fluoro-N4-[4-(N-methylamino)sulfonyl-3-methoxyphenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,28(s, 1H), 8,42(d, 1H, J=3.0 Hz), 7,71(d, 1H, J=1.8 Hz), to 7.67(d, 1H, J=8,4 Hz), 7,46(DD, 1H, J=1.5 and 8.4 Hz), to 6.95(d, 1H, J=5.4 Hz), a 3.87(s, 3H), 2,38(of 2.38(d, 3H, J=4,8 Hz); LC/MS: purity: 80%, MS(mass/charge): 349(M+2).--
503N2-(3,5-Acid)-5-fluoro-N4-[2-(2-hydroxyethyloxy)pyrid-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,34(s, 1H), 9,14(s, 1H), to 8.57(d, 1H, J=2.7 Hz), 8,08(d, 1H, J=3.0 Hz), 7,98(DD, 1H, J=2.7 and 8.7 Hz), 6,91(d, 2H, J=1,8 Hz), 6,77(d, 1H, J=8.7 Hz), 6,03(t, 1H, J=3.6 Hz), 4,23(t, 2H, J=4.5 Hz), of 3.69(m, 2H), the 3.65(s, 3H), 3,62 (s, 3H); LC/MS: purity: 96%; MS(mass/charge): 401(M+).++-
504N2-(3, 5dimethylphenyl)-5-fluoro-N4-[2-(2-hydroxyethyloxy)pyrid-5-yl]-2,4-pyrimidinediamine1H NMR(D IS CO-d6): d of 9.30(s, 1H), 9,06(s, 1H), 8,54(d, 1H, J=2.4 Hz), of 8.06(d, 1H, J=3.6 Hz), 7,94(DD, 1H, J=2.7 and 9.0 Hz), 7,20(d, 2H, J=0.9 Hz), 6,79(d, 1H, J=9.0 Hz), 6,50(s, 1H), and 4.8(t, 1H, J=5.7 Hz), to 4.23(t, 2H, J=5,7 Hz), 3,70(square, 2H, =4,8 Hz)of 2.16 (s, 6N); LC/MS: purity: 100%; MS(mass/charge): 369(M+).++-
505N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-[2-(2-hydroxyethyloxy)pyrid-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 9.35(s, 1H), 9,17(s, 1H), 8,49(s, 1H), 8,07(d, 1H, J=3.6 Hz), 7,98(DD, 1H, J=2.7 and 9.0 Hz), 7,81(s, 1H), 7,40(userd, 1H, J=8.7 Hz), 6,98(d, 1H, J=8,4 Hz), to 6.80(d, 1H, J=8.7 Hz), a 4.83(t, 1H, J=5.7 Hz), 4,24(t, 1H, J=4,8 Hz),of 3.77 (s, 3H), of 3.69 (q, 2H, J=4,8 Hz); LC/MS: purity: 100%; MS(mass/charge): 406(MH+).++-
506N2-Allyl-N4-(3,4-atlanticcity)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 7.70(d, 1H, J=4.4 Hz), to 7.68(m, 2H), 7,66(DD, 1H, J=1.2 and 7.8 Hz), to 5.85(m, 1H), 5,10(DD, 1H, J=1.5 and a 16.8 Hz), 5,00(DD, 1H, J=1.8 and 12.0 Hz), 4,22(s, 4H), 3,83(t, 2H, J=4.5 Hz), or 3.28(s, 3H); LC/MS: purity: 100%; MS(mass/charge): 317(MH+).--
507N2-(3,5-Di is ethoxyphenyl)-5-fluoro-N4-[4-(N-methylamino)sulfonyl-3-methoxyphenyl]-2,4-pyrimidinediamine LC/MS: purity: 80%, MS(mass/charge): 464(MH+).++-
508N2-(3,5-Acid)-5-fluoro-N4-(3-methylpiperid-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,50(s, 1H), which 9.22(s, 1H), 8,16(s, 1H), 8,13(DD, 1H, J=0.9 and 6.6 Hz), of 8.06(d, 1H, J=8.7 Hz), 7,55(userid, 1H, J=5.7 Hz), 6,94(d, 2H, J=1.2 Hz), 6,07(t, 1H, J=1.2 Hz), 3,68(s, 3H), 3,66(s, 3H), 2.49 USD(C, 6H); LC/MS: purity: 96%; MS(mass/charge): 356(MH+).++-
509N2-(3, 5dimethylphenyl)-5-fluoro-N4-(3-methylpiperid-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,46(s, 1H), 9,14(s, 1H), 3,17(users, 1H), 8,13(d, 1H, J=3.3 Hz), of 8.04(d, 1H, J=8,4 Hz), 7,55(DD, 1H, J=2.1 and 8.4 Hz), 7,24(s, 2H), 6,24(s, 1H), 3.33 and(s, 3H), of 3.32(s, 3H), 2,18(s, 3H); LC/MS: purity: 93%, MS(mass/charge): 324(MH+).++-
510N4-(5-Chloropyrid-2-yl)-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 93%, MS(mass/charge): 376(MH+).++
5115-fluoro-N4-(3-hydroxyphenyl)-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,39(s, 1H), of 9.30(s, 1H), which 9.22(s, 1H), 8,29(users, 1H), 8,14(s, 1H), 8,11(d, 1H, J=3,9 Hz), of 7.90(DD, 1H, J=1,2 and 9.0 Hz), to 7.50(DD, 1H, J=1.5 and 6.3 Hz), 7,33(m, 3H), to 7.09(t, 1H, J=2.1 and Hz), 7,01(t, 1H, J=8.1 Hz), 6,45 (DD, 1H, J=1.5 and 7.8 Hz); LC/MS: purity: 98%; MS(mass/charge): 364(MH+).+
512N4-(3,4-Atlanticcity)-5-fluoro-N2-[3-(1,2,4-oxadiazol-3-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,54(s, 1H), 9,26(s, 1H), 8,18(s, 1H), 8,10(d, 1H, J=2.4 Hz), 7,83(userd, 1H, J=8.1 Hz), 7,38(t, 1H, J=7.8 Hz), 7,27(m, 2H), 7,13(userd, 1H, J=8.7 Hz), PC 6.82(d, 1H, J=9.0 Hz), 4,22(, 4H); LC/MS: purity: 91%; MS(mass/charge): 406(M+).+-
513N4-(3,4-Acid)-5-fluoro-N2-[3-(1,2,4-oxadiazol-3-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d at 9.53(s, 1H), 9,29(s, 1H), 8,21(s, 1H), 8,10(d, 1H, J=3,9 Hz), 7,79(DD, 1H, J=1,2 and 8.4 Hz), 7,33(m, 3H), 7,16(s, 1H), 6,94(d, 1H, J=8.7 Hz in), 3.75(s, 3H), 3,70(s, 3H); LC/MS: purity: 95%, MS(mass/charge): 407(MH-).+ -
514N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(1,2,4-oxadiazol-3-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,6(s, 1H), 9,49(s, 1H), 9,40(s, 1H), 8,15(d, 1H, J=8.1 Hz), 8,11(d, 1H, J=3,9 Hz), 7,85(userd, 1H, J=8,4 Hz), 7,29(m, 3H), 7,13(d, 1H, J=2.4 Hz), 6,91(DD, 1H, J=3.0 and an 8.4 Hz), 5,73(d, 1H, J=3.6 Hz), 1,40(s, 3H); LC/MS: purity: 91%; MS(mass/charge): 446(M-).+-
515N4-(3,4-Acid)-5-fluoro-N2-[5-methoxycarbonyl-3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d being 9.61(s, 1H), 9,27(s, 1H), to 8.62(s, 1H), scored 8.38(s, 1H), 8,17(d, 1H, J=0.9 Hz), to 8.12(d, 1H, J=3.6 Hz), of 8.04(d, 1H, J=1.5 Hz), 7,35(m, 2H), 7,27(m, 1H), 6,76(d, 1H, J=7.8 Hz), 3,82(s, 3H), 3,70(s, 3H), of 3.65(s, 3H); LC/MS: purity: 99%; MS(mass/charge): 466(MH+).+-
516N4-(3,4-Atlanticcity)-5-fluoro-N2-[5-methoxycarbonyl-3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d for 9.64(s, 1H), 9,23(s, 1H), 8,61(s, 1H), of 8.37(s, 1H), 8,19(s, 1H), 8,12(d, 1H, J=3.3 Hz), with 8.05(s, 1H), 7,38(m, 2H), 7,22(DD, 1H, J=2.7 and 8.7 Hz), 6,70(d, 1H, J=8.7 Hz), 5,74(s, 1H),4,15(s, 4H), 3,85(s, 3H); LC/MS: purity: 98%; MS(mass/charge): 464(MH+).--
517N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[5-methoxycarbonyl-3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,51(s, 1H), 9,54(s, 1H), 9,40(s, 1H), 8,63(s, 1H), 8,39(s, 1H), 8,18(s, 1H), 8,14(d, 1H, J=3,9 Hz), of 8.04(s, 1H), 7,44(DD, 1H, J=2.1 and 8.7 Hz), 7,37(s, 1H), 6,77(d, 1H, J=8.4 and Hz), of 3.84(s, 3H), of 1.38(s, 6H); LC/MS: purity: 90%; MS(mass/charge): 505(MH+).--
5185-fluoro-N4-(3-hydroxyphenyl)-N2-[5-methoxycarbonyl-3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d for 9.64(s, 1H), 9,25(s, 1H), to 8.62(s, 1H), 8,43(s, 1H), 8,19(s, 1H), 8,15(d, 1H, J=3,9 Hz), with 8.05(s, 1H), 7,38(s, 2H), was 7.36(s, 2H), 7,13(s, 1H), 6,98(t, 1H, J=8.7 Hz), 6.42 per(DD, 1H, J=2.4 and 6.6 Hz), 3,83(s, 3H); LC/MS: purity: 98%; MS(mass/charge): 422(M+).+-
519N4-(3,4-Atlanticcity)-5-fluoro-N2-[3-(oxazol-2-yl)-5-triptoreline]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.75(s, 1H), 9,23 ° C, 1H), 8,59(s, 1H), they were 8.22(t, 2H, J=0.9 Hz), 8,14(d, 1H, J=3,9 Hz), 7,69(s, 1H), 7,40(s, 1H), 7,31(d, 1H, J=2.4 Hz), 7,19(DD, 1H, J=2.7 and 9.0 Hz), 6,72(d, 1H, J=8,4 Hz), 4,17(s, 4H); LC/MS: purity: 92%; MS(mass/charge): 474(MH+).+-
520N4-(3,4-Acid)-5-fluoro-N2-[3-(oxazol-2-yl)-5-triptoreline]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,73(s, 1H), 9,31(s, 1H), to 8.57(s, 1H), 8,24(s, 1H), 8,20(users, 1H), 8,14(d, 1H, J=4, 2 Hz), 7,68(s, 1H), 7,40(s, 1H), 7,33(userid, 1H, J=9.0 Hz), 7.23 percent(users, 1H), PC 6.82(d, 1H, J=7.5 Hz), 3,71(s, 3H), 3,68(s, 3H); LC/MS: purity: 97%; MS(mass/charge): 476(MH+).+-
521N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)-5-triptoreline]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,54(s, 1H), to 9.70(s, 1H), 9,42(s, 1H), 8,54(s, 1H), of 8.27(s, 1H), 8,21(s, 1H), 8,16(d, 1H, J=2.7 Hz), to 7.67(s, 1H), 7,40(d, 1H), 7,33(userid, 1H, J=8,4 Hz), 7,17(d, 1H, J=2.4 Hz), for 6.81(d, 1H, J=8,4 Hz)of 1.39(s, 6H); LC/MS: purity: 100%; MS(mass/charge): 515(MH+).+-
5225-fluoro-N4-(3-hydroxyphenyl-N2-[3-(1,2,4-oxadiazol-3-yl)phenyl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d of 9.55(s, 1H), 9,36(s, 1H), of 9.30(s, 1H), 8,13(m, 2H), 7,88(userd, 1H, J=7.8 Hz), 7,38(t, 1H, J=7.8 Hz), 7,27(m, 2H), 7,13(t, 1H, J=7.8 Hz), 7,02(s, 1H), 6,50(userid, 1H, J=5.7 Hz); LC/MS: purity: 95%; MS(mass/charge): 364(M+).+
5232-Chloro-5-fluoro-N4-methyl-N4-(3,4,5-trimethoxyphenyl)-4-pyrimidinamine1H NMR(DMSO-d6): d 8,11(d, 1H, J=5.4 Hz), 6,79(s, 2H), 3,74(s, 3H), and 3.72(s, 3H), of 3.65(s, 3H), 3,38(s, 3H); LC/MS: purity: 94%; MS(mass/charge): 329(MH+).-
5245-fluoro-N4-(5-methylisoxazol-3-yl)-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,45(s, 1H), 9,59(s, 1H), with 8.33(s, 1H), 8,21(d, 1H, J=2.7 Hz), 8,18(s, 1H), 7,83(userd, 1H, J=7,2 Hz), 7,55(userd, 1H, J=8.1 Hz), 7,40(t, 1H, J=8.1 Hz), 7,35(s, 1H, J=6,92(s, 1H), to 2.29 (s, 3H); LC/MS: purity: 100%, MS(mass/charge): 353 (MH+).+
5255-fluoro-N4-(5-methyl-3-phenylisoxazol-4-yl)-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d was 9.33(s, 1H), and 9.0(s, 1H), 8,23(s, 1H), 8,14(users, 1H), of 8.09(d, 1H, J=3.6 Hz), 7,66(m, 3H), 7,43(m, 4H), 7,32(s, 1H), 7,24(t, 1H, J=7,2 Hz), a 2.36(s, 3H); LC/MS: purity: 85%, MS(mass/charge): 429(MH+).+
5265-fluoro-N4-(1-methyl-3-phenylpyrazol-5-yl)-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,48(m, 2H), 8,19(m, 2H), 8,11(m, 2H), to 7.77(m, 2H), 7,35(m, 6H), 6.73 x(s, 1H), 3,32(s, 3H); LC/MS: purity: 83%, MS(mass/charge): 428(MH+).+
527N2,N4-Bis[3-methoxycarbonyl-5-(oxazol-2-yl)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.89(s, 1H), 9,83(s, 1H), 8,58(s, 1H), 8,49(s, 1H), 8,46(s, 1H), 8,35(s, 1H), 8,27(d, 1H, J=3.6 Hz), 8,08(m, 3H), 7,30(s, 1H), 7,27(s, 3H), 3,71(s, 3H), 3,68(s, 3H); LC/MS: purity: 86%), MS(mass/charge): 531(MH+).+
528N2,N4-Bis(3,5-dimethylisoxazol-4-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 8,76(s, 1H), 8,13(s, 1H), 7,83(d, 1H, J=3,9 Hz), 2,19(s, 3H), 2,10(s, 3H), 2,03(s, 3H), of 1.85(s, 3H); LC/MS: purity: 91%; MS(mass/charge): 319(MH+). -
529N2,N4-Bis[3-(oxazol-2-yl)-5-triptoreline]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,99(s, 1H), 9,19(s, 1H), at 8.60(s, 1H), 8,54(s, 1H), 8,31(d, 1H, J=2.7 Hz), 8,11(d, 1H, J=5,1 Hz), with 8.05(s, 1H), 7,79(s, 1H), to 7.61(s, 1H), 7,31(s, 1H), 7,27(s, 1H); LC/MS: purity: 92%, MS(mass/charge): 551(MH+).+
530N2-[(2-tert-Butyl-1,3,4-oxadiazol-5-yl)phenyl]-N4-(3,4-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,43(s, 1H), 9,23(s, 1H), of 8.25(s, 1H), 8,08(d, 1H, J=3.6 Hz), 7,93(userd, 1H, J=8.7 Hz), 7,49 (userd, 1H, J=7.5 Hz), 7,35(m, 2H), 7,25(d, 1H, J=2.4 Hz), 6.75 in(d, 1H, J=8.7 Hz), 3,70(, 3H), 3,66(s, 3H), of 1.37(s, 9H).+++
531N2-[(2-tert-Butyl-1,3,4-oxadiazol-5-yl)phenyl]-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.45(s, 1H), 9,19(s, 1H), 8,25(t, 1H, J=1.8 Hz), 8,07(d, 1H, J=3.3 Hz), 7,87(userd, 1H, J=2.4 Hz), 7,51(userd, 1H, J=7.8 Hz), 7,40(m, 2H), 7,16(DD, 1H, J=2.4 and 8.7 Hz), 6,70(d, 1H, J=9 Hz), 4,15(m, 4H), to 1.37(s, 9H); LC/MS: purity: 95%; MS(mass/charge): 463(MH+)./td> +
532N2-[(2-tert-Butyl-1,3,4-oxadiazol-5-yl)phenyl]-5-fluoro-N4-(3-hydroxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.45(s, 1H), 9.28 are(s, 1H), 9,23(s, 1H), 8,24(s, 1H), 8,11(d, 1H, J=3,9 Hz), 8,00(userd, 1H, J=8.1 Hz), 7,50(d, 1H, J=7.8 Hz), 7,39(t, 1H, J=8,4 Hz), 7,30(userd, 1H, J=8,4 Hz), 7,12(t, 1H, J=2.1 Hz), of 6.99(t, 1H, J=8,4 Hz), to 6.43(DD, 1H, J=1.8 and an 8.4 Hz)to 1.38 (s, N); LC/MS: purity: 93%; MS(mass/charge): 421(MH+).+
533N4-(3,4-Atlanticcity)-5-fluoro-N4-methyl-2-hydrazine-4-pyrimidinamine1H NMR(DMSO-d6): d to 7.61(d, 1H, J=5.4 Hz), 6,86(m, 1H), 6,69(m, 2H), 4,29(s, 4H), 3,51(s, 3H); LC/MS: purity:90%, MS(mass/charge): 292(MH+).-
534N4-(3,5-Dimethylisoxazol-4-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 9.35(s, 1H), 8,88(s, 1H), 8,31(s, 1H), 8,14(s, 1H), 8,10(d, 1H, J=3.6 Hz), 7,71(userd, 1H, J=7.8 Hz), was 7.45(d, 1H, J=6.6 Hz), 7,32(d, 1H, J=0.9 Hz), 7,29(t, 1H, J=8.1 Hz), 2,87(, 3H), 2,10(s, 3H); LC/MS: purity: 96%; MS(mass/dawn is): 367(MH+). +
535N4-(3,5-Dimethylisoxazol-4-yl)-5-fluoro-N2-[5-methoxycarbonyl-3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamineLC/MS: purity: 85%, MS(mass/charge): 425(MH+).+
536N2-(3,5-Dimethyl-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR(DMSO-d6): d 11,16(s, 1H), 10,00(s, 1H), 9,52(s, 1H), 8,16(d, 1H, J=4, 2 Hz), 7,46(m, 2H), 7,35(d, 1H, J=8.1 Hz), 7,13(s, 2H), was 7.08(d, 1H, J=2.4 Hz), 3,60(s, 3H), of 2.28(s, 3H), and 2.14(s, 6H)that was 1.43(s, 6H); LC/MS: purity: 99%, MS(mass/charge): 439.-
537N2-(3,5-Dimethyl-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine salt benzosulfimide acid1H NMR(DMSO-d6): d 11,19(s, 1H), 10,52(s, 1H), 9,65(s, 1H), 8,19(d, 1H, J=4.5 Hz), 7,56(m, 2H), 7,44(d, 1H, J=8,4 Hz), 7,35(d, 1H, J=8,4 Hz), 7,30(m, 3H), 7,10(s, 2H), 3,60(s, 3H), and 2.14(s, 6H)that was 1.43(s, 6H); LC/MS: purity: 93%, MS(m is SSA/charge): 439 (MH+, for parentline ion).-
538N2-(3,5-Dimethyl-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine salt methanesulfonic acid1H NMR(DMSO-d6): d RS 11.80(s, 1H), 10,16(s, 1H), 9,73(s, 1H), 8,21(d, 1H, J=4, 2 Hz), 7,44(d, 1H, J=8,4 Hz), was 7.36(d, 1H, J=8,4 Hz), 7,12(s, 2H), 3,60(s, 3H), 2,32(s, 3H), 2.13 and(s, 6H), USD 1.43(s, 6H); LC/MS: purity: 97%, MS(mass/charge): 439(MH+, for parentline ion).-
539N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(2-trifluoromethyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR(DMSO-d6): d 10,67(s, 1H), or 10.60(s, 1H), of 10.05(s, 1H), to 8.20(d, 1H, J=4,8 Hz), to 7.84(s, 1H), 7.62mm(d, 1H, J=9 Hz), 7,45(userd, 2H, J=7.8 Hz), 7.23 percent(d, 1H, J=8.7 Hz), to 7.15(s, 1H), to 7.09(d, 1H, J=7,8 Hz), 6,85(d, 1H, J=8.7 Hz), 2,28(s, 3H), 1,38 (C, 6N); LC/MS: purity: 99%; MS(mass/charge): 488(MH+, for parentline ion).+
540N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxaz the n-6-yl)-5-fluoro-N2-(2-trifluoromethyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine salt benzosulfimide acid 1H NMR(DMSO-d6): d 10,66(s, 1H), and 10.20(s, 1H), 9,90(s, 1H), 8,17(d, 1H, J=4.5 Hz), 7,88(s, 1H), EUR 7.57(m, 3H), of 7.48(d, 1H, J=8,4 Hz), 7,29(m, 4H), to 7.15(s, 1H), 6,85(d, 1H), J=8,4 Hz); LC/MS: purity: 95%, MS(mass/charge): MH+, for parentline ion).+
541N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(2-trifluoromethyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine salt methanesulfonic acid1H NMR(DMSO-d6): d 10,67(s, 1H), 10,45(s, 1H), 10,19(s, 1H), 8,23(d, 1H, J=5,1 Hz), 7,80(s, 1H), 7.62mm(d, 1H, J=8.7 Hz), was 7.45(d, 1H, J=8,4 Hz), 7,11 (s, 1H), 6,85(d, 1H, J=8,4 Hz), of 2.38(s, 3H), 1,37(s, 6H); LC/MS: purity: 99%, MS(mass/charge): 488(MH+, for parentline ion+
542N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(2-trifluoromethyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine cleaners containing hydrochloride salt1H NMR(DMSO-d6): d at 10.64(s, 1H), 9,90(s, 1H), 9,80(s, 1H), 8,15(d, 1H, J=4,8 Hz), of 7.96(s, 1H), to 7.59(d, 1H, J=8.7 Hz), to 7.50(DD, 1H, J=1.5 and 9.3 Hz), 7,25(m, 2H), 6.87 in(d, 1H, J=8,4 Hz); LC/MS: purity: 99%, MS(mass/charge): 488(MH+, for parentline ion).+the
543N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamineLC/MS: purity: 98%; MS(mass/charge): 470(MH+);+++
544N4-(2-Amino-3-methoxy-pyrid-6-yl)-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 92%; MS(mass/charge): 387(MH+)+
545N4-(2-Amino-3-methoxyphenyl-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamineLC/MS: purity: 94%; MS(mass/charge): 417(MH+)+
546N4-(2-Amino-3-methoxyphenyl-6-yl)-5-fluoro-N2-(2-methoxycarbonylmethyl-5-yl)-2,4-pyrimidinediamineLC/MS: purity: 82%; MS(mass/charge):425(MH+)+
547N4-(2-Amino-3-methoxyphenyl-6-yl)-5-fluoro-N2[3-(N-methylaminoanthraquinone)phenyl]-2,4-pyrimidinediamineLC/MS: purity: 89%; MS(mass/charge): 414(MH+)+
548N2-(3,5-Dichloro-4-hydroxyphenyl)-N4-(3,5-dichloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 92%; MS(mass/charge):465(MH+)++
549N4-(4-Acetyl-2,2-dimethyl-3-occupied[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamineLC/MS: purity: 97%; MS(mass/charge): 513(M+)
550N4-Acetyl-N4-(2,2-dimethyl-3-oxo-4H-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamineLC/MS: purity: 96%; MS(mass/charge): 513(M+)
551N2-Acetyl-N4-(2,2-dimethyl-3-oxo-4H-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamineLC/MS: purity: 95%; 514(MH+)
5522,N4-Bis[3-methyl-4-(4-methylpiperazine)phenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 99%; MS(m/e):506(MH+)
553N4-(3, 5dimethylphenyl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,14(users, 1H), 9,04(s, 1H), of 8.06(d, J=3,9 Hz, 1H), 7,40 and 7.36(m, 2H), 6,95(s, 2H), to 6.67(s, 1H), to 3.58 of 3.56(m, 9H), are 2.19(s, 6H); LC/MS: purity: 96%; MS(mass/charge): 399(MH+).+
554N2-(3-Chloro-4-hydroxy-5-were)-5-fluoro-N4-(3, 5dimethylphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.21(users, 1H), 9,04(users, 1H), 8,63(users, 1H), with 8.05(d, J=3.6 Hz, 1H), 7,53-7,49(m, 1H), 7,34-7,30(m, 2H), 7.24 to 7,20(m, 1H), 6,69(users, 1H), 2,22s, 6H), is 2.09(s, 3H); LC/MS: purity: 93%; MS(mass/charge): 373(MH+).+
555N2-[3,5-Bis(hydroxymethyl)phenyl]-N4-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,11(s, 2H), of 8.06(d, J=3,9 Hz, 1H), 7,45(s, 2H), 7,38(s, 2H), 6,85(s, 1H), of 6.68(s, 1H), to 4.38-4,34(m, 4H), 2,22(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 369(MH+).+
556N2-(3,5-Dichlorophenyl)-N4-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,76(users, 1H), 9,51(users, 1H), 8,18 (d, J=3,9 Hz, 1H), 7,73-of 7.69(m, 2H), 7,29-7,25(m, 2H),? 7.04 baby mortality(t, J=1.8 Hz, 1H), 6.75 in(s, 1H, in), 2.25(s, 6H); LC/MS: purity: 92%; MS(mass/charge): 378(MH+).++
557N4-(3, 5dimethylphenyl)-5-fluoro-N2-[2-(N-methylamino)carbanilide-7-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,66(s, 1H), 9,37(s, 1H), 9.28 are(s, 1H), 8,48-to 8.40(m, 1H), 8,13(d, J=3.6 Hz, 1H), 7,98-7,88(m, 1H), 7,33(s, 2H), 7,22(d, J=7.8 Hz, 1H),? 7.04 baby mortality(d, J=1.8 Hz, 1H), 6.90 to(t, J=8,1 Hz. 1H), of 6.71(s, 1H), 2,80(d, J=3.0 Hz, 3H), of 2.23 (s, 6 who); LC/MS: purity: 99%; MS(mass/charge): 405(MH+).-
5585-fluoro-N4-(3-methoxy-5-triptoreline)-N2-[2-(N-methylamino)carbanilide-7-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,57(s, 1H), 9,65(s, 1H), 9,40(s, 1H), 8,39-8,35(m, 1H), 8,15(d, J=3,9 Hz, 1H), 7,78(d, J=7.5 Hz, 1H), 7,73-of 7.69(m, 1H), EUR 7.57-7,52(m, 1H), 7,18(d, J=7.8 Hz, 1H), 9,98(d, J=1,8 Hz, 1H), 6.87 in-to 6.80(m, 2H), 3,70(s, 3H), 2,74 (d, J=4.5 Hz, 3H); 19F NMR (282 MHz, DMSO-d6): -61,70, -162,97; LC/MS: purity: 99%; MS(mass/charge): 475(MH+).+
559N2-(3,5-Dichloro-4-hydroxyphenyl)-N4-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,49(s, 1H), of 9.21(s, 1H), 9,19(s, 1H), 8,08(d, J=3.3 Hz, 1H), 7,66(d, J=1.5 Hz, 2H), 7,29(s, 2H), 6,70(s, 1H), 2,24(s, 6H); LC/MS: purity: 95%; MS(mass/charge): 394(MH+).++
560N2-(4-Chloro-3, 5dimethylphenyl)-N4-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,17(s, 1H), 9,13(s, 1H), 8,07(d, J=3,9 Hz, 1H), 7,45(s, 2H), 7,30(s,2H), 6,72(s, 1H), 2,22(s, 6H), to 2.18(s, 6H); LC/MS: purity: 93%; MS(mass/charge): 372(MH+).-
561N4-[3,4-(Diversitronics)phenyl]-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d at 9.53(s, 1H), 9,13(s, 1H), 8.17-a to 8.12(m, 1H), 8,11(d, J=3,9 Hz, 1H), 7,42(DD, J=2.4 and 9.0 Hz, 1H), 7,32(d, J=8,4 Hz, 1H), 7,00(s, 2H), to 3.64(s, 6H); 19F NMR(282 MHz, DMSO-d6): -49,77, -164,19; LC/MS: purity: 93%; MS(mass/charge): 451 (MH+).+
562N4-[3,4-(Diversitronics)phenyl]-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,54(s, 1H), which 9.22(s, 1H), 8,12(d, J=3.6 Hz, 1H), 8,11-8,08(m, 1H), 7,42(DD, J=2.1 and 9.0 Hz, 1H), 7,32(d, J=8.7 Hz, 1H), make 6.90(d, J=2.1 Hz, 2H), 6,07(t, J=2.4 Hz, 1H), 3,65(s, 6H); 19F NMR(282 MHz, DMSO-d6): -49,69, -163,86; LC/MS: purity: 96%; MS(mass/charge): 421(MH+).++
563N4-[3,4-(Diversitronics)phenyl]-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.51(s, 1H) 9,13(s, 1H), 8,11(d, J=3.6 Hz, 1H), 8,09-of 8.06(m, 1H), 7,39(DD, J=2.1 and 8.7 Hz, 1H), 7,34(d, J=9.0 Hz, 1H), 7,22(s, 2H), 6,53(s, 1H), 2,16(s, 6H); 19F NMR(282 MHz, DMSO-d6): -49,67, -164,51; LC/MS: purity: 98%; MS(mass/charge): 389(MH+).++
564N2-(3,5-Dichloro-4-hydroxyphenyl)-N4-[3,4-(diversitronics)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,59(s, 1H), 9,45(users, 1H), 9,31(s, 1H), 8,08(d, J=3.6 Hz, 1H), 7,85-7,79(m, 1H), 7,55(s, 1H), 7,29(s, 1H); 19F NMR(282 MHz, DMSO-d6): -49,50, -163,68; LC/MS: purity: 96%; MS(mass/charge): 446(MH+).+
565N2-(3,5-Dichlorophenyl)-N4-[3,4-(diversitronics)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,62-9,68(m, 2H), 8,19(d, J=3.6 Hz, 1H), 7,92-7,88(m, 1H), 7,71(s, 1H), of 7.70(s, 1H), 7,38-7,33(m, 2H), 7,00(t, J=1.8 Hz, 1H); 19F NMR(282 MHz, DMSO-d6): -49,51, -162,64; LC/MS: purity: 99%; MS(the mass/charge): 430(MH+).+
566N2-(4-Chloro-3, 5dimethylphenyl)-N4-[3,4-(diversitronics)phenyl]-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,84(s, 1H), 9,51(s, 1H), 8,18(s, J=2.7 Hz, 1H), 7,99(users, 1H), 7,41-7,35(m, 4H), 2,22(s, 6H); LC/MS: purity: 94%; MS(mass/charge): 424(MH+).-
567N2-(3-Chloro-4-hydroxy-5-were)-N4-[3,4-(diversitronics)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.57(s, 1H), 9,14(s, 1H), 8,58(users, 1H), with 8.05(d, J=3,9 Hz, 1H), of 7.90(s, 1H), 7,44(d, J=1.8 Hz, 1H), 7,31(DD, J=1.8 and 8.7 Hz, 1H), 7,26(d, J=8,4 Hz, 1H), 7,14-to 7.09(m, 1H), 2.06 to(C, 3H); 19F NMR(282 MHz, DMSO-d6): -49,60, -164,34; LC/MS: purity: 97%; MS(mass/charge): 425(MH+).+
568N4-[3,4-(Diversitronics)phenyl]-5-fluoro-N2-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 9.60(s, 1H), of 9.56(s, 1H), 8,17(d, J=3.3 Hz, 1H), 8,00(s, 1H), 7,66(s, 1H), 7,52(s, 1H), 7,41-7,31(m, 2H), 6,72(s, 1H), 3,74(s, 3H); 19F NMR(282 MHz, DMSO-d6): -49,75, -61,96, -162,93; LC/MS: purity: 93%; MS(mass/charge): 459(MH+).-
569N4-[3,4-(Diversitronics)phenyl]-5-fluoro-N2-(3-methyl-5-thrift methylphenyl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d to 9.66(s, 1H), 9,59(s, 1H), 8,19(d, J=3.6 Hz, 1H), 8,04-of 7.97(m, 1H), 7,84(users, 1H), 7,68(users, 1H), was 7.36(users, 2H), 7,03(s, 1H), to 2.29(s, 3H); 19F NMR(282 MHz, DMSO-d6): -49,63, -61,86, -163,10; LC/MS: purity: 98%; MS(mass/charge): 443(MH+).+
570N4-[3,4-(Diversitronics)phenyl]-5-fluoro-N2-[2-(N-methylamino)carbanilide-7-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 11.56(s, 1H), 9,63(s, 1H), 9,34(s, 1H), 8,44 is 8.38(m, 1H), 8,12(d, J=3.6 Hz, 1H), 7,97(users, 1H), 7,84 for 7.78(m, 1H), 7,38-7,32(m, 1H), 7,26(d, J=9.0 Hz, 1H), 7,20(d, J=8,1 Hz, 1H), of 7.00(s, 1H), 6.87 in(t, J=7.8 Hz, 1H), 2,74(d, J=3,6 Hz, 3H); 19 NMR (282 MHz, DMSO-d6): -49,66, -163,58; LC/MS: purity: 99%; MS(mass/charge): 457(MH+).+
571N4-(3-Chloro-4-methoxyphenyl)-N2-[3,5-dimethyl-4-(N-methylamino)carbonintensity]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9.28 are(s, 1H), 9,03(s, 1H), 8,15-8,07(m, 1H), with 8.05(d, J=3.3 Hz, 1H), 7,76-7,72(m, 2H), 7.68 per-of 7.60(m, 1H), 7.23 percent(s, 2H), to 7.09(d, J=9.0 Hz, 1H), 4,10(s, 2H), 3,83(s, 3H), 2,69(d, J=4,2 Hz, 3H), 2,11(s, 6H); LC/MS: purity: 99%; 461 (MH+).++
572N2-[3,5-dimethyl-4-(N-methylamino)carbonintensity]-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d the remaining 9.08(s, 1H), of 8.95(s, 1H), 8,14-of 8.06(m, 1H), 8,00(d, J=3.6 Hz, 1H), 7.23 percent-of 7.25(m, 3H), 7,20-7,14(m, 1H), 6,78(d, J=8.7 Hz, 1H), is 4.21(s, 4H), 4,11(s, 2H), 2,69(d, J=4.5 Hz, 3H), to 2.13(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 454 (MH+).++
573N4-(3,5-Acid)-N2-[3,5-dimethyl-4-(N-methylamino)carbonintensity]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,20(s, 1H), 9,01(s, 1H), 8,14-with 8.05(m, 2H), 7,29(s, 2H), 7,00-of 6.96(m, 2H), 6,24-to 6.19(m, 1H), 4,11(s, 2H), to 3.67(s, 6H), 2,70(d, J=4,8 Hz, 3H), 2,12(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 456(MH+).++
574N2-[3,5-dimethyl-4-(N-methylamino)carbonintensity]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,59(s, 1H), to 9.32(s, 1H), of 8.95(s, 1H), 8,11-of 8.06(m, 1H), 8,04(d, J=3,9 Hz, 1H), 7,34-of 7.23(m, 3H), 7,21-to 7.18(m, 1H), 6.87 in(d, J=9.0 Hz, 1H), 4,10(s, 2H), 2,69(d, J=4,8 Hz, 3H), 2,11(s, 6H), of 1.40(s, 6H); LC/MS: purity: 95%; MS(mass is/charge): 495(MH+). ++
575N2-[3,5-dimethyl-4-(N-methylamino)carbonintensity]-5-fluoro-N4-(3,4-methylenedioxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.15(s, 1H), 8,96(s, 1H), 8,12-with 8.05(m, 1H), 8,01(d, J=3,9 Hz, 1H), 7,44-7,40(m, 1H), 7,25(s, 2H), 7,15-7,07(m, 1H), at 6.84(d, J=8,1 Hz, 1H), 5,98(s, 2H), 4,11(s, 2H), 2,69(d, J=4,8 Hz, 3H), 2.13 and(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 440(MH+).++
5762-Chloro-5-fluoro-N4-(2-isopropoxyphenyl-5-yl)-N4-methyl-4-pyrimidinamine1H NMR(DMSO-d6): d 8,17(d, J=2.7 Hz, 1H), 8,14(d, J=5.4 Hz, 1H), 7,74(DD, J=2.7 and 8.7 Hz, 1H), 6,77(DD, J=0.6 and 8.7 Hz, 1H), total of 5.21(quintet, J=6.3 Hz, 1H), 3,38(s, 3H), of 1.29(d, J=6.3 Hz, 6H); LC/MS: purity: 95%; MS(mass/charge): 298(MH+).--
577N4-(3-Chloro-4-methoxyphenyl)-N2-(3,5-acid)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 7.95(d, J=5.7 Hz, 1H), 7,46(d, J=2.7 Hz, 1H), 7,28(DD, J=2.4 and 9.0 Hz, 1H), 7,13(d, J=9.0 Hz, 1H), 6,98(s, 1H), 6,97(s, 1H), 6,09-the 6.06(m, 1H), 3,86(s, 3H), of 3.69(s, 6H), 3,44(3H); LC/MS: purity: 96%; MS(mass/charge): 419(MH+).+-
578N2-(3-Chloro-4-methoxy-5-were)-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,41(s, 1H), to 7.99(d, J=6.3 Hz, 1H), 7,69(d, J=2.7 Hz, 1H), 7,47(d, J=2.4 Hz, 1H), was 7.36(d, J=1.8 Hz, 1H), 7,28(DD, J=2.7 and 8.7 Hz, 1H), 7,14(d, J=8.7 Hz, 1H), a 3.87(s, 3H), 3,68(, 3H), 3,42(s, 3H), 2,19(s, 3H); LC/MS: purity: 86%; MS(mass/charge): 438(MH+).+-
579N4-(3-Chloro-4-methoxyphenyl)-N2-[3,5-dimethyl-4-(N-methylamino)carbonintensity]-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,24(s, 1H), 8,16-of 8.04(m, 1H), of 7.96(d, J=6.0 Hz, 1H), 7,47(d, J=2.4 Hz, 1H), 7,31-7,24(m, 3H), 7,15(d, J=8.7 Hz, 1H), 4,12(s, 2H), a 3.87(s, 3H), 3,42(s, 3H), 2,69(d, J=4,8 Hz, 3H), of 2.15(s, 6H); LC/MS: purity: 92%; MS(mass/charge): 475(MH+).+-
580N4-(3-Chloro-4-methoxyphenyl)-N2-[3-(N-methylamino)carbonintensity]-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,whirs, 1H), 8,02(d, J=6.3 Hz, 1H), 8,00-of 7.97(m, 1H), 7,50(d, J=2.7 Hz, 1H), was 7.36-7,34(m, 1H), 7,33-7,20(m, 3H), 7,16(d, J=9.0 Hz, 2H), 6,57-of 6.52(m, 1H), to 4.41(s, 2H), a 3.87(s, 3H), 3,44(s, 3H), 2,64(d, J=4,8 Hz, 3H); LC/MS: purity: 94%; MS(mass/charge): 447(MH+).+-
581N2-(3,5-Acid)-5-fluoro-N4-(2-isopropoxyphenyl-5-yl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d for 9.47(users, 1H), 8,14(d, J=2.7 Hz, 1H), to 7.99(d, J=6.0 Hz, 1H), 7,71(DD, J=3.0 and 8.7 Hz, 1H), of 6.96-6,93(m, 2H), 6,77(DD, J=0.6 and 8.7 Hz, 1H), 6,12(t, J=2.1 Hz, 1H), total of 5.21(quintet, J=6.3 Hz, 1H), 3,70(s, 6H), of 3.45(s, 3H), of 1.29 (d, J=6.3 Hz, 6N); LC/MS: purity: 93%; MS(mass/charge): 414(MH+).+-
5825-fluoro-N4-(2-isopropoxyphenyl-5-yl)-N4-methyl-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d at 9.53(s, 1H), 8,14(d, J=3.0 Hz, 1H), 8,02-to 7.93(m, 2H), of 7.70(DD, J=2.7 and 8.7 Hz, 1H), 7,37(t, J=2.1 Hz, 1H), 7,26-7,20(m, 1H), 7,13(t, J=8,1 Hz, 1H), 6,78(d, J=8.7 Hz, 1H), 6,56-6,50(m, 1H), 5,22(quintet, J=6.0 Hz, 1H), and 4.40 (s, 2H), 3,44 (s, 3H), of 2.64 (d, J=4,8 Hz, 3H), of 1.30 (d, J=6.0 Hz, 6N); LC/MS: purity: 95%; MS(mass/charge): 441(MH+).+-
583N2-(3, 5dimethylphenyl)-5-fluoro-N4-(2-isopropoxyphenyl-5-yl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,42(s, 1H), 8,14(d, J=2.7 Hz, 1H), 8,01(d, J=6,6 Hz, 1H), 3.45 points(s, 3H), 2,19(s, 6H), of 1.29(d, J=6.3 Hz, 6H), of 7.70(DD, J=2.7 and 8.7 Hz, 1H), 7,24(s, 2H), 6,77(d, J=8,4 Hz, 1H), 6,57(s, 1H), 5,22(quintet, J=6.3 Hz, 1H); LC/MS: purity: 96%; MS(mass/charge): 382(MH+).+-
584N4-(3-Chloro-4-methoxyphenyl)-N2-(3, 5dimethylphenyl)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d is 9.09(s, 1H), 7,94(d, J=6.0 Hz, 1H), 7,45(d, J=2.1 Hz, 1H), 7,31-of 7.23(m, 3H), 7,13(d, J=9.0 Hz, 1H), 6,51(s, 1H), 3,86(s, 3H), 3,42(s, 3H), of 2.18(s, 6H); LC/MS: purity: 88%; MS(the mass/charge): 387(MH+).+-
585N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(2-methoxycarbonylmethyl-5-yl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.45(s, 1H), 8,16(d, J=1.8 Hz, 1H), with 8.05(d, J=6.0 Hz, 1H), 7,68(DD, J=2.1 and 9.0 Hz, 1H), 7,65(d, J=0.9 Hz, 1H), 7,63-EUR 7.57(m, 1H), 7,54(d, J=2.7 Hz, 1H), 7,35(DD, J=2.7 and 8.7 Hz, 1H), of 7.23(d, J=8.7 Hz, 1H), 3,95(s, 3H), of 3.94 (s, 3H), 3,51 (d, J=1.2 Hz, 3H); LC/MS: purity: 91%; MS(mass/charge): 457(MH+).- -
5865-fluoro-N4-(2-isopropoxyphenyl-5-yl)-N2-(2-methoxycarbonylmethyl-5-yl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,39(s, 1H), 8,13(d, J=2.4 Hz, 1H), of 8.09(d, J=1.8 Hz, 1H), 7,98(d, J=6.3 Hz, 1H), of 7.70(DD, J=3.0 and 8.7 Hz, 1H), of 7.64-EUR 7.57(m, 2H), 7,54(d, J=8.7 Hz, 1H), 6,79(d, J=8.7 Hz, 1H), 5,22(quintet, J=6.3 Hz, 1H), a 3.87(s, 3H), of 3.45 (s, 3H), of 1.31 (d, J=6.3 Hz, 6N), LC/MS: purity: 93%; MS(mass/charge): 452(MH+).++
587N4-(4-Chloro-3-methoxyphenyl)-N2-(3,5-acid)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,44(users, 1H), 8,03(d, J=6.0 Hz, 1H), 7,40(d, J=8,1 Hz, 1H), 7,15(d, J=2.1 Hz, 1H), 6,95(d, J=1.2 Hz, 2H), 6.90 to(DD, J=2.1 and 8.4 Hz, 1H), 6,12-between 6.08(m, 1H), 3,82(s, 3H), of 3.69(s, 6H), to 3.49(s, 3H); LC/MS: purity: 96%; MS(mass/charge): 420(MH+).++-
588N4-(4-Chloro-3-methoxyphenyl)-N2-(3, 5dimethylphenyl)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,35(users, 1H), 8,03(d, J=6,0, 1H), 7,41(d, J=8,4, 1H), 7,26-of 7.23(m, 2H), 7,16(d, J=2.4 Hz, 1H), 6.90 to(DD, J=2.1 and 8.7 Hz, 1H), 6,58-6,55(m, 1H), 3,82(s, 3H), 3,49(s, 3H), 2,19(who, 6H); LC/MS: purity: 91%; MS(mass/charge): 387(MH+).+-
589N4-(4-Chloro-3-methoxyphenyl)-5-fluoro-N4-methyl-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,34(s, 1H), 8,00(d, J=5,4, 1H), 7,93-of 8.00(m, 1H), 7,44(t, J=1.8 Hz, 1H), 7,39(d, J=8,4 Hz, 1H), 7,26(DD, J=1,2 and 8.4 Hz, 1H), 7,15 for 7.12(m, 1H), to 7.09(d, J=8,4 Hz, 1H), 6.87 in(DD, J=2.1 and 9.0 Hz, 1H), 6,47(DD, J=2.7 and 7.2 Hz, 1H), 4,39 (s, 2H), 3,82 (s, 3H), of 3.48 (s, 3H), of 2.64 (d, J=4.5 Hz, 3H); LC/MS: purity: 98%; MS(mass/charge): 447(MH+).++-
590N4-(4-Chloro-3-methoxyphenyl)-5-fluoro-N2-(indol-5-yl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,84(s, 1H), 9,010(s, 1H), of 7.96(d, J=5.4 Hz, 1H), 7,87-to 7.84(m, 1H), 7,39(d, J=8,1 Hz, 1H), 7,27-7,19(m, 3H), 7,12(d, J=2.1 Hz, 1H), 6.87 in(DD, J=2.4 and 8.7 Hz, 1H), 6,29-of 6.25(m, 1H), is 3.82(s, 3H), 3,47(s, 3H); LC/MS: purity: 97%; MS(mass/charge): 399(MH+).++-
591N4-(4-Chloro-3, 5dimethylphenyl)-N2-(3,5-acid)-5-fluoro-N4-methyl-2,4-pyrimidinediamineNAMR(DMSO-d6): d 9,51(users, 1H), 8,03(d, J=6.0 Hz, 1H), 7,19(s, 2H), 6,93(d, J=1.8 Hz, 2H), 6,12(t, J=2.4 Hz, 1H), 3,70(s, 6H), of 3.46(s, 3H), 2,32(s, 6H); LC/MS: purity: 98%; MS(mass/charge): 418(MH+).++-
592N4-(4-Chloro-3, 5dimethylphenyl)-N2-(3, 5dimethylphenyl)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,49(users, 1H), 8,04(d, J=6.0 Hz, 1H), 7,24(s, 2H), 7,20(s, 2H), 6,60(s, 1H), 3.45 points(s, 3H), 2,32(s, 6H), are 2.19(s, 6H); LC/MS: purity: 98%; MS(mass/charge): 386(MH+).--
593N4-(4-Chloro-3, 5dimethylphenyl)-5-fluoro-N4-methyl-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.32(s, 1H), 7,98(d, J=5.7 Hz, 1H), 8,00-a 7.92(m, 1H), 7,44(t, J=2.1 Hz, 1H), 7,29-of 7.23(m, 1H), 7,16(s, 2H), 7,10(t, J=8,1 Hz, 1H), 6,47(DD, J=2.4 and 7.8 Hz, 1H), 4,39(s, 2H), 3,44(s, 3H), of 2.64(d, J=4.5 Hz, 3H), 2,32(C, 6N); LC/MS: purity: 98%; MS(mass/charge): 445(MH+).++-
594N4-(4-Chloro-3, 5dimethylphenyl)-5-fluoro-N2-(indol-5-yl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,84(s, 1H), 8,98(1H), 7,94(d, J=5.7 Hz, 1H), to 7.84(s, 1H), 7,29-7,19(m, 3H), 7,15(s, 2H), of 6.26(t, J=2.1 Hz, 1H), 3,42(s, 3H), 2,32(s, 6H); LC/MS: purity: 94%; MS(mass/charge): 397(MH+).+++
595N4-(4-Chloro-3, 5dimethylphenyl)-5-fluoro-N2-(2-methoxycarbonylmethyl-5-yl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,43(s, 1H), 8,17(d, J=1.8 Hz, 1H), 8,01(d, J=5.4 Hz, 1H), 7.68 per-to 7.61(m, 2H), 7,55(d, J=9,3 Hz, 1H), 7,17(s, 2H), a 3.87(s, 3H), of 3.45(s, 3H), 2,32(s, 6H); LC/MS: purity: 97%; MS(the mass/charge): 457(MH+).--
596N4-(4-Chloro-3, 5dimethylphenyl)-5-fluoro-N4-methyl-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.66(s, 1H), 8,11(d, J=0,90 Hz, 1H), 8,04(d, J=5.4 Hz, 1H), 7,81(s, 4H), 7,28(d, J=0.6 Hz, 1H), 7,18(s, 2H), 3.46 in(s, 3H), of 2.33(s, 6H); LC/MS: purity: 89%; MS(mass/charge): 425(MH+).--
597N4-(4-Chloro-3, 5dimethylphenyl)-5-fluoro-N4-methyl-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,71(s, 1H), 8,40(s, 1H), 8,24-8,18(m, 1H), of 8.06(d, J=6.0 Hz, 1H), to 7.59-7,53(m, 2H) 7,34-7,29(m, 2H), 7,20(s, 2H), 3,49(s, 3H), 2,32(s, 6H); LC/MS: purity: 96%; MS(mass/charge): 425(MH+).+-
598N4-(4-Chloro-3, 5dimethylphenyl)-5-fluoro-N4-methyl-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d for 9.64(s, 1H), 8,35(s, 1H), 8,04(d, J=5.7 Hz, 1H), 7,76(d, J=8.7 Hz, 2H), EUR 7.57(d, J=8.7 Hz, 2H), 7,49(s, 1H), 7,19(s, 2H), 3.46 in(s, 3H), 2,32(s, 6H); LC/MS: purity: 96%; MS(mass/charge): 425(MH+).+-
599N4-(4-Chloro-3, 5dimethylphenyl)-5-fluoro-N2-(indol-6-yl)-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,00(s, 1H), 9,58(users, 1H), 8,00(d, J=6.0 Hz, 1H), 7,89(s, 1H), 7,41(d, J=8,4 Hz, 1H), 7.24 to to 7.18(m, 3H), 7,11(DD, J=1,8 and 8.4 Hz, 1H), 6,35 of 6.31(m, 1H), 3,47(s, 3H), of 2.33(s, 6H); LC/MS: purity: 95%; MS(mass/charge): 397(MH+).+-
600N4-[3-Chloro-4-(N-methylamino)carbonintensity]-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,94(users, 1H), 9,65(users, 1H), 8,18(d, J=4,2 Hz, 1H), 7,93-to 7.84(m, 1H), 7,74(d, J=2.4 Hz, 1H), 7,66(DD, J=2.7 ,0 Hz, 1H), 7,12(s, 2H), 6,99(d, J=9.0 Hz, 1H), only 6.64(s, 1H), 4,55(s, 2H), 2,66(d, J=4,8 Hz, 3H), 2,18(C, 6N), LC/MS: purity: 91%; MS(mass/charge): 431(MH+).++-
601N4-[3-Chloro-4-(N-methylamino)carbonintensity]-N2-(3,5-dimethoxyphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,52(users, 1H), of 9.30(users, 1H), 8,11(d, J=3,9 Hz, 1H), 7,92-a 7.85(m, 1H), 7,79(d, J=2.4 Hz, 1H), 7,74(DD, J=2.7 and 8.7 Hz, 1H), of 6.96(d, J=9.0 Hz, 1H), 6,85(d, J=1.8 Hz, 2H), 6,10(t, J=the 2.4 Hz, 1H), of 4.54(s, 2H), to 3.64(s, 6H), to 2.67 (d, J=4.5 Hz, 3H); LC/MS: purity: 93%; MS(mass/charge): 463(MH+).++-
602N2-(3-Chloro-4-methoxyphenyl)-N4-[3-chloro-4-(N-methylamino)carbonintensity]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,45(users, 1H), 9,25(users, 1H), 8,03(d, J=3.3 Hz, 1H), 7,86 for 7.78(m, 1H), of 7.70(d, J=2.4 Hz, 1H), to 7.64(d, J=2.4 Hz, 1H), 7,58(DD, J=2.7 and 9.3 Hz, 1H), of 6.96(d, J=9,3 Hz, 1H), 6,93(d, J=9,3 Hz, 1H), 4,48(s, 2H), of 3.73(s, 3H), 2,60 (d, J=4.5 Hz, 3H); LC/MS: purity: 95%; MS(mass/charge): 467(MH+).++-
603N2-(4-Chloro-3,5-dim is terphenyl)-N4-[3-chloro-4-(N-methylamino)carbonintensity]-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,45(users, 1H), 9,2=8(users, 1H), 8,11(d, J=3,9 Hz, 1H), 7,92-7,87(m, 1H), of 7.75(d, J=2,4, 1H), 7,68(DD, J=2.7 and 9.3 Hz, 1H), 7,40(s, 2H), 6,99(d, J=8.7 Hz, 1H), of 4.54(s, 2H), 2,67(d, J=4,2 Hz, 3H), 2,22(s, 6H); LC/MS: purity: 95%; MS(mass/charge): 464(MH+).+--
604N4-(4-Chloro-3, 5dimethylphenyl)-5-fluoro-N4-methyl-N2-[4-(oxazol-4-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,42(s, 1H), 8,46-8,43(m, 1H), 8,39-of 8.37(m, 1H), 8,00(d, J=5.4 Hz, 1H), 7,73(d, J=9.0 Hz, 2H), 7.62mm(d, J=9.0 Hz, 2H), 7,17(s, 2H), 3.45 points(s, 3H), 2,32(s, 6H); LC/MS: purity: 96%; MS(mass/charge): 424(MH+).+-
605N4-[3-Chloro-4-(N-methylamino)carbonintensity]-5-fluoro-N2-(indol-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,80(s, 1H), 9,26(s, 1H), 9,07(s, 1H), of 8.06(s, J=3,9 Hz, 1H), 7,93 to 7.75(m, 4H), of 7.36(d, J=8,4 Hz, 1H), 7,22-to 7.15(m, 2H), 6,95(d, J=8.7 Hz, 1H), 6,33-6,27(m, 1H), of 4.54(s, 2H), to 2.67(d, J=4,2 Hz, 3H); LC/MS: purity: 96%; MS(mass/charge): 441(MH+).++-
606N4-(4-Chloro-3-methoxyphenyl)-5-fluoro-N4-m is Teal-N2-[4-(oxazol-4-yl)phenyl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,44(s, 1H), 8,44(d, J=0,90 Hz, 1H), scored 8.38(d, J=0,90 Hz, 1H), 8,02(d, J=5.7 Hz, 1H), 7,73(d, J=8.7 Hz, 2H), 7,63(d, J=8.7 Hz, 2H), 7,41(d, J=8,4 Hz, 1H), 7,14(d, J=2.4 Hz, 1H), 6,92-6,86(m, 1H), 3,83(s, 3H), 3,49(s, 3H); LC/MS: purity: 97%; MS(mass/charge): 426(MH+).+++
607N4-(4-Chloro-3-methoxyphenyl)-N2-[4-chloro-3-(N-methylamino)carbonitril]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,70(users, 2H), 8,23-8,18(m, 1H), 8,15(d, J=4,2 Hz, 1H), 7,71(d, J=2.7 Hz, 1H), 7,54(DD, J=2.7 and 9.0 Hz, 1H), 7,45(DD, J=2.4 and 8.7 Hz, 1H), 7,35(d, J=2.4 Hz, 1H), 7,28(d, J=8.7 Hz, 1H), from 7.24(d, J=9.0 Hz, 1H), of 3.73(s, 3H), 2,65 (d, J=4.5 Hz, 3H); LC/MS: purity: 92%; MS(mass/charge): 436(M+).++-
608N4-[3-Chloro-4-(N-methylamino)carbonintensity]-N2-[4-chloro-3-(N-methylamino)carbonitril]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d at 9.53(users, 1H), 9,49(users, 1H), 8,28-8,21(m, 1H), 8,13(d, J=3,9 Hz, 1H), 7,93-7,87(m, 1H), to 7.77-to 7.64(m, 4H), 7,28(d, J=8.7 Hz, 1H), 6,98(d, J=9.0 Hz, 1H), 4,59(s, 2H), 2,70(d, J=4,8 Hz, 3H), to 2.67(d, J=4.5 Hz, 3H); LC/MS: purity: 94%; MS(mass/charge): 494(MH+).+-
609N2-[4-Chloro-3-(N-methylamino)carbonitril]-N4-(4-chloro-3-triptoreline)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,84(s, 1H), 9,59(s, 1H), 8,35-of 8.27(m, 2H), 8,23(d, J=3,9 Hz, 1H), of 8.06(d, J=2.7 Hz, 1H), of 7.75(d, J=2.4 Hz, 1H), to 7.67-of 7.60(m, 2H), 7,29(d, J=9.0 Hz, 1H), 2,71(d, J=4.5 Hz, 3H); LC/MS: purity: 92%; MS(mass/charge): 475(MH+).++-
610N4-(4-Chloro-3, 5dimethylphenyl)-N2-[4-chloro-3-(N-methylamino)carbonitril]-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.55(s, 1H), 8.30 to-8,24(m, 1H), 8,01(d, J=6,6 Hz, 1H), 7,86(d, J=2.7 Hz, 1H), 7,68(DD, J=2.7 and 9.0 Hz, 1H), 7,27(d, J=8.7 Hz, 1H), 7,16(s, 2H), 3,42(s, 3H), of 2.72(d, J=4.5 Hz, 3H), 2,32(s, 6H); LC/MS: purity: 98%; MS(mass/charge): 448(M+).--
611N4-(4-Chloro-3-methoxyphenyl)-N2-[3-chloro-4-(N-methylamino)carbonitril]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.57(s, 1H), 9,54(s, 1H), 8,19(d, J=3.6 Hz, 1H), 8,15-8,08(m, 1H), to 7.93(d, J=2.1 Hz, 1H), 7,51(DD, J=2.4 and 8.7 Hz, 1H), 7,47(DD, J=2,45 and 8.7 Hz, 1H), 7,43(d, J=2.1 Hz, 1H), 7,34(d, J=8.7 Hz, 1H), 7,27(d, J=8,4 Hz, 1H), 3,80 (s, 3H), of 2.72 (d, J=4.5 Hz, 3H); LC/MS: purity: 99%; MS(mass/charge): 436(M). ++-
612N2-[3-Chloro-4-(N-methylamino)carbonitril]-N4-(4-chloro-3-triptoreline)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,83(s, 1H), 9,65(s, 1H), 8,33 compared to 8.26(m, 1H), 8,25(d, J=3.6 Hz, 1H), 8,16-8,11(m, 1H), of 8.06(d, J=2.7 Hz, 1H), 7,87(d, J=1.8 Hz, 1H), 7,66(d, J=8.7 Hz, 1H), 7,52(DD, J=1.8 and an 8.4 Hz, 1H), 7,28(d, J=8,4 Hz, 1H), 2,72(d, J=4.5 Hz, 3H); LC/MS: purity: 97%; MS(mass/charge): 474(M+).++-
613N4-(4-Chloro-3, 5dimethylphenyl)-N2-[3-chloro-4-(N-methylamino)carbonitril]-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.66(s, 1H), 8.17-a of 8.09(m, 1H), with 8.05(d, J=5.4 Hz, 1H), 7,94(d, J=2.1 Hz, 1H), 7,54(DD, J=2.1 and 8.4 Hz, 1H), 7,28(d, J=8,1 Hz, 1H), 7,18(s, 2H), 3,44(s, 3H), 2,71(d, J=4.5 Hz, 3H), 2,32(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 448(M+).+-
614N4-[3-Chloro-4-(methoxycarbonyl)methylenediphenyl]-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,28(s, 1H), of 10.05(s, 1H), compared to 8.26(d, J=4,8 Hz, 1H), 7,74(d, J=2.7 Hz, 1H), EUR 7.57(DD, J2,7 and 8.7 Hz, 1H), 7,10-7,01(m, 3H), 6,69(s, 1H), is 4.93(s, 2H), 3,70(s, 3H), 2,17(s, 6H); LC/MS: purity: 98%; MS(mass/charge): 431(MH+).+++
615N4-[3-Chloro-4-(methoxycarbonyl)methylenediphenyl]-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.75(s, 1H), at 9.53(s, 1H), 8,15(d, J=4.5 Hz, 1H), 7,80(d, J=2.7 Hz, 1H), 7,66(DD, J=2.7 and 9.0 Hz, 1H), 7,00(d, J=9.0 Hz, 1H), for 6.81(d, J=2.4 Hz, 1H), 6,14(t, J=2.1 Hz, 1H), 4,90(, 2H), 3,71(s, 3H), of 3.64(s, 6H); LC/MS: purity: 98%; MS(mass/charge): 463(MH+).+++
616N4-[3-Chloro-4-(methoxycarbonyl)methylenediphenyl]-N2-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,63(s, 1H), 9,41(s, 1H), 8,12(d, J=4,2 Hz, 1H), 7,76(d, J=2.7 Hz, 1H), 7,69(d, J=2.4 Hz, 1H), 7,60(DD, J=2.4 and 9.0 Hz, 1H), 7,44(DD, J=2.7 and 8.7 Hz, 1H),? 7.04 baby mortality(d, J=8.7 Hz, 1H), 7,02(d, J=9.0 Hz, 1H), 4,90(s, 2H), 3,80 (s, 3H), 3,70 (s, 3H); LC/MS: purity: 92%; MS(mass/charge): 467(M+).+++
617N2-(4-Chloro-3, 5dimethylphenyl)-N4-[3-chloro-4-(methoxycarbonyl)methylenediphenyl]-5-fluoro-2,pyrimidinediamine 1H NMR(DMSO-d6): d for 9.64(s, 1H), to 9.45(s, 1H), 8,14(d, J=4,2 Hz, 1H), of 7.75(d, J=2.4 Hz, 1H), to 7.61(DD, J=2.4 and 9.0 Hz, 1H), 7,38(s, 2H), 7,02(d, J=9.0 Hz, 1H), 4,91(s, 2H), 3,70(s, 3H), of 2.21(s, 6H); LC/MS: purity: 95%; MS(mass/charge): 465(M+).+++
618N4-[3-Chloro-4-(methoxycarbonyl)methylenediphenyl]-5-fluoro-N2-(indol-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,86(s, 1H), 9,23(s, 1H), to 8.94(s, 1H), 8,03(d, J=3,9 Hz, 1H), 7,83(d, J=2.4 Hz, 1H), 7,79(s, 1H), 7,68(DD, J=2.4 and 9.0 Hz, 1H), 7,25-7,21(m, 3H), 6,93(d, J=9.0 Hz, 1H), 6,27(t, J=2.4 Hz, 1H), 4,89(s, 2H), 3,71(s, 3H); LC/MS: purity: 95%; MS(mass/charge): 442(MH+).++-
619N4-[3-Chloro-4-(2-hydroxyethyloxy)phenyl]-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,63(users, 1H), 9,34(users, 1H), 8,11(d, J=4,2 Hz, 1H), 7,72(d, J=2.7 Hz, 1H), to 7.64(DD, J=2.7 and 9.0 Hz, 1H), 7,12(d, J=8.7 Hz, 1H), return of 6.58(s, 1H), of 4.05(t, J=5,1 Hz, 2H), of 3.73(t, J=5,1 Hz, 2H), 2,16(s, 6H); LC/MS: purity: 91%; MS(mass/charge): 403(MH+).+++
620N4-[3-Chloro-4-2-hydroxyethyloxy)phenyl]-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,29(s, 1H), 9,13(s, 1H), 8,08(d, J=3.6 Hz, 1H), of 7.75(d, J=2.7 Hz, 1H), 7,71(DD, J=2.7 and 8.7 Hz, 1H), was 7.08(d, J=9.0 Hz, 1H), make 6.90(d, J=2.1 Hz, 2H), equal to 6.05(t, J=2.1 Hz, 1H), 4,89(t, J=5,1 Hz, 1H), of 4.05(t, J=5,1 Hz, 2H), of 3.73 (q, J=5,1 Hz, 2H), 3,63 (C, 6N); LC/MS: purity: 99%; MS(mass/charge): 435(MH+).+++
621N4-[3-Chloro-4-(2-hydroxyethyloxy)phenyl]-N2-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,29(s, 1H), 9.15, with(s, 1H), of 8.06(d, J=3.6 Hz, 1H), 7,74(d, J=2.1 Hz, 2H), 7,63(DD, J=2.7 and 9.0 Hz, 1H), 7,46(DD, J=2.7 and 9.0 Hz, 1H), 7,10(d, J=9.0 Hz, 1H), 7,00(d, J=9.0 Hz, 1H), 4,87(t, J=5.4 Hz, 1H), of 4.05(t, J=5 Hz, 2H), of 3.78 (s, 3H), 3,74 (kV, J=4,8 Hz, 2H); LC/MS: purity: 100%; MS(mass/charge): 441(MH+).++-
622N2-(4-Chloro-3, 5dimethylphenyl)-N4-[3-chloro-4-(2-hydroxyethyloxy)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,31(s, 1H), 9,18(s, 1H), 8,08(d, J=3,9 Hz, 1H), 7,72(d, J=2.7 Hz, 1H), 7,63(DD, J=2.4 and 9.0 Hz, 1H), 7,42(s, 2H), 7,12(d, J=9.0 Hz, 1H), 4,87(t, J=5.7 Hz, 1H), Android 4.04(t, J=5,1 Hz, 2H), of 3.73(sq, J=5,1 Hz, 2H), 2,20(C, 6N); LC/MS: purity: 99%; MS(mass/charge): 438(MH+).++-
623N4-[3-Chloro-4-(2-hydroxyethyloxy)phenyl]-5-fluoro-N2-(indol-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,84(s, 1H), 9,17(s, 1H), of 8.90(s, 1H), 8,01(d, J=3,9 Hz, 1H), 7,82-7,76(m, 2H), to 7.67(DD, J=3.0 and 9.3 Hz, 1H), 7,25-7,21(m, 3H), 7,03(d, J=9.0 Hz, 1H), 6,28 and 6.25(m, 1H), 4,87(t, J=5.4 Hz, 1H), Android 4.04(t, J=5,1 Hz, 2H), of 3.73 (q, J=5,1 Hz, 2H); LC/MS: purity: 100%; MS(mass/charge): 414(MH+).+++
624N4-[3-Chloro-4-(2-hydroxyethyloxy)phenyl]-N2-(4-chloro-3-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,49(s, 1H), 9,42(s, 1H), 8,12(d, J=3,9 Hz, 1H), 7,80(d, J=2.4 Hz, 1H), to 7.59(DD, J=2.7 and 9.0 Hz, 1H), 7,40 and 7.36(m, 1H), 7,30(DD, J=2.7 and 8.4 Hz, 1H), 7,20(d, J=8.7 Hz, 1H), 7,12(d, J=8.7 Hz, 1H), 4,06(t, J=4,8 Hz, 2H), of 3.77-3,71 (m, 2H), 3,66 (s, 3H); LC/MS: purity: 93%; MS(mass/charge): 440(MH+).++-
625N4-[3-Chloro-4-(N-methylamino)carbonintensity]-5-fluoro-N2-(indol-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,84(s, 1H), 9,20(s, 1H), 8,91(s, 1H), 8,02 (d, J=3,9 Hz, 1H), of 7.90-of 7.82(m, 2H), 7,73(DD, J=2.4 and 9.0 Hz, 1H), 7,26-7,19(m, 3H), 6,93(d, J=8.7 Hz, 1H), 6,28(t, J=2.4 Hz, 1H), to 4.52(s, 2H), to 2.67(d, J=4.5 Hz, 3H); LC/MS: pure is a: 98%; MS(mass/charge): 441(MH+).+++
6262-Chloro-N4-(4-chloro-3, 5dimethylphenyl)-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(DMSO-d6): d 8,17(d, J=5,1 Hz, 1H), 7.23 percent(s, 2H), 3,38(s, 3H), 2,32(s, 6H); LC/MS: purity: 98%; MS(mass/charge): 301(MH+).-+
6272-Chloro-5-fluoro-N4-methyl-N4-[3,4-(tetrafluoroethoxy)phenyl]-4-pyrimidinamine1H NMR(DMSO-d6): d 7,94(d, J=4,8 Hz, 1H), 7,17(d, J=9.6 Hz, 1H), 7,17(d, J=9.6 Hz, 1H), 7,05-7,00(m, 2H), 3,50(s, 3H); LC/MS: purity: 92%; MS(mass/charge): 368(MH+).--
6282-Chloro-N4-[3,4-(diversitronics)phenyl]-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(DMSO-d6): d of 7.82(d, J=4.5 Hz, 1H), 6,98(d, J=8,4 Hz, 1H), 6.90 to-6,83(m, 2H), 3,40(s, 3H); LC/MS: purity: 100%; MS(mass/charge): 318(MH+).--
629N4-(chlor-3-triptoreline)-5-fluoro-N2-(indol-6-yl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 10,86(s, 1H), 9,67(s, 1H), 9,14(s, 1H), 8,44(DD, J=2.4 and 9.0 Hz, 1H), 8,15(d, J=3,9 Hz, 1H), 8,12(d, J=2.7 Hz, 1H), to 7.77(s, 1H), 7,51(d, J=9,3 Hz, 1H), 7,37(d, J=8,4 Hz, 1H), 7,19(t, J=2.1 Hz, 1H), 7,14(DD, J=1,8 and 8.4 Hz, 1H), 6,34-6,30 (m, 1H); LC/MS: purity: 100%; MS(mass/charge): 422(MH+).++-
630N4-(4-Chloro-3-methoxyphenyl)-5-fluoro-N2-(indol-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,85(s, 1H), 9,35(s, 1H), 9,04(s, 1H), 8,10(d, J=3.6 Hz, 1H), 7,79(s, 1H), 7,62-EUR 7.57(m, 2H), was 7.36(d, J=8,4 Hz, 1H), 7,24(d, J=9.0 Hz, 1H), 7,19(t, J=2.7 Hz, 1H), 7,15(DD, J=the 1.8 and 8.4 Hz, 1H), 6,34-6,30(m, 1H), to 3.67 (s, 3H); LC/MS: purity: 99%; MS(mass/charge): 384(MH+).++-
631N4-(3-Chloro-4-methoxycarbonylaminophenyl)-5-fluoro-N2-(indol-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,78(s, 1H), 9,23(s, 1H), 9,03(s, 1H), with 8.05(d, J=3.6 Hz, 1H), a 7.85(d, J=2.7 Hz, 1H), 7,79-7,73(m, 2H), was 7.36(d, J=8,4 Hz, 1H), 7,19(DD, J=2.1 and 8.7 Hz, 1H), 7,16(t, J=3.0 Hz, 1H), to 6.95(d, J=9.0 Hz, 1H), 6,32-6,28(m, 1H), 4,88 (s, 2H), 3,71 (s, 3H); LC/MS: purity: 98%; MS(mass/charge): 442(MH+).+++
632N4-[3-Chloro-4-(2-hydroxyethyloxy)phenyl]-5-fluoro-N2-(indol-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,79(s, 1H), 9,19(d, J=1.2 Hz, 1H), 9,01(s, 1H), 8,04( d, J=3.6 Hz, 1H), to 7.84(d, J=2,7, 1H), 7,79-7,73(m, 2H), was 7.36(d, J=8,4 Hz, 1H), 7,19(DD, J=1,8 and 8.4 Hz, 1H), 7,16( t, J=2,4 Hz, 1H), 7,05(d, J=9,3 Hz, 1H), 6,32-6,28 (m, 1H), a 4.86 (t, J=5,1 Hz, 1H), Android 4.04 (t, J=5.4 Hz, 2H), of 3.73 (q, J=5,1 Hz, 2H); LC/MS: purity: 99%; MS(mass/charge): 414(MH+).++-
6335-fluoro-N2-[3-(oxazol-2-yl)phenyl]-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,76(s, 1H), 9,63(s, 1H), 8,33-8,29(m, 1H), they were 8.22(d, J=3.6 Hz, 1H), 8,16-8,13(m, 1H), 7,78-7,74(m, 1H), 7.62mm(DD, J=2.4 and 9.0 Hz, 1H), 7,58-7,53(m, 1H), 7,42-7,31(m, 3H); LC/MS: purity: 92%; MS(mass/charge): 478(MH+).+-
6345-fluoro-N4-methyl-N2-[3-(oxazol-2-yl)phenyl]-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,67(s, 1H), to 8.57(t, J=1.8 Hz, 1H), 8,18-8,16(m, 1H), of 8.09(d, J=5.7 Hz, 1H), 7,72-7,66(m, 1H), 7,60(d, J=1.8 Hz, 1H), 7,54-7,47(m, 2H), 7,39-to 7.32(m, 3H), 3,53(s, 3H); LC/MS: purity: 96%; MS(mass/charge): 492(MH+).--
635N2-[3,5-Dimethyl-4-(N-methylamino)carbonintensity]-N4-(3,4-atlanticcity)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.02(s, 1H), 8,12-of 8.06(m, 1H), 7,88(d, J=5.7 Hz, 1H), 7,34(s, 2H), 6,83(d, J=6,9 Hz, 1H), PC 6.82(s, 1H), 6.73 x(DD, J=3.0 and 9.0 Hz, 1H), 4,24(s, 4H), 4,11(s, 2H), 3,38(s, 3H), 2,69(d, J=4,8 Hz, 3H), of 2.16(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 468(MH+).+++
636N2-[3,5-Dimethyl-4-(N-methylamino)carbonintensity]-5-fluoro-N4-methyl-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.15(s, 1H), 8,12-with 8.05(m, 1H), 8,02(d, J=5.7 Hz, 1H), 8,02(d, J=5.7 Hz, 1H), 7,55(DD, J=0.9 and 2.7 Hz, 1H), of 7.48(d, J=9,3 Hz, 1H), 7,31(s, 2H), 7,27(DD, J=0.9 and 2.1 Hz, 1H), 4,11(s, 2H), 3.46 in(s, 3H), 2,69(d, J=4,8 Hz, 3H), and 2.14 (s, 6N); LC/MS: purity: 99%; MS(mass/charge): 540(MH+).+++
637N2-[3,5-Dimethyl-4-(N-methylamino)carbonintensity]-5-fluoro-N4-[3,4-(tetrafluoroethoxy)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,59(s, 1H), 9,14(s, 1H), 8,16 was 8.8(m, 3H), to 7.61(DD, J=2.7 and 9.0 Hz, 1H), 7,40(d, J=9.0 Hz, 1H), 7,25(s, 2H), 4,12(s, 2H), 2,69(d, J=4,8 Hz, 3H), of 2.15(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 526(MH+).+-
638N2-[3,5-Dimethyl-4-(N-methylamino)carbonintensity]-N4-(3,5-acid)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,07(s, 1H), 8,13-with 8.05(m, 1H), 7,94(d, J=5.7 Hz, 1H), 7,35(s, 2H), 6,44(DD, J=0.6 and 2.4 Hz, 2H), 6,39(t, J=2.4 Hz, 1H), 4.16 the(s, 2H), and 3.72(s, 6H), 3.43 points(s, 3H), 2,69(d, J=4,8 Hz, 3H), of 2.16(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 470(MH+).+++
639N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(methoxycarbonylmethylene)indol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d or 10.60(s, 1H), to 9.45(s, 1H), which is 9.09(s, 1H), 8,04(d, J=3.6 Hz, 1H), EUR 7.57(s, 1H), 7,40-7,33(m, 2H), 7,31-7,24(m, 2H), 7,20(d, J=3.3 Hz, 1H), for 6.81(d, J=8.7 Hz, 1H), 3,35(d, J=2.4 Hz, 1H), 4,91(s, 2H), 3,63(s, 3H), of 1.40(s, 6H); LC/MS: purity: 97%; MS(mass/charge): 491(MH+).++-
640N4-[3-Chloro-4-(N-methylamino)carbonintensity]-ftor-N2-[1-(methoxycarbonylmethylene)indol-6-yl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,42(s, 1H), 9,24(s, 1H), 8,07(d, J=3,9 Hz, 1H), 7,92-to 7.84(m, 2H), 7,71(DD, J=2.7 and 9.3 Hz, 1H), 7,55(s, 1H), 7,41(d, J=8,4 Hz, 1H), 7,29(DD, J=1.5 and 8.4 Hz, 1H), 7,20(d, J=3.3 Hz, 1H), 6,94(d, J=9.0 Hz, 1H), 6,36 (d, J=3.3 Hz, 1H), 4.92 in (c, 2H), 4.53-in (c, 2H), 3,63 (c, 3H), to 2.67 (d, J=4.5 Hz, 1H); LC/MS: purity: 99%; MS(mass/charge): 514(MH+).++-
641N4-(4-Chloro-3-methoxyphenyl)-5-fluoro-N2-[1-(methoxycarbonylmethylene)indol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,34(s, 1H), 9,10(s, 1H), of 8.09(d, J=3.6 Hz, 1H), 7,62-to 7.59(m, 1H), 7,54(d, J=2.4 Hz, 1H), 7,49(DD, J=2.4 and 8.4 Hz, 1H), 7,38(d, J=8.7 Hz, 1H), 7,27-7,22(m, 2H), 7,20(d, J=3.3 Hz, 1H), 6,36(DD, J=0.6 and 3.0 Hz, 1H), 4,88 (s, 2H), 3,62 (s, 3H), of 3.60 (s, 3H); LC/MS: purity: 98%; MS(mass/charge): 457(MH+).+++
642N4-(3,4-Atlanticcity)-5-fluoro-N2-[1-(methoxycarbonylmethylene)indol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,19(s, 1H), 9,14(s, 1H), 8,02(d, J=3,9 Hz, 1H), 7,63(s, 1H), 7,40-7,31(m, 2H), 7,30-7,17(m, 3H), 6,74(d, J=9.0 Hz, 1H), 6.35mm(d, J=2.7 Hz, 1H), 4,90(s, 2H), is 4.21(s, 4H), 3,63(s, 3H); LC/MS: purity: 93%; MS(mass/charge): 450(MH+).++-
643N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(methoxycarbonylmethylene)indol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,56(s, 1H), 9,20(s, 1H), 8,79(s, 1H), 8,00(d, J=3.6 Hz, 1H), 7,86(s, 1H), 7,33(DD, J=2.1 and 8.7 Hz, 1H), 7,27-7,16(m, 4H), 6,83(d, J=8.7 Hz, 1H), 6,27(d, J=3.0 Hz, 1H), of 5.05(s, 2H), 3,66(s, 3H), of 1.40(s, 6H); LC/MS: purity: 96%; MS(mass/charge): 491(MH+).++-
644N4-[3-Chloro-4-(N-methylamino)carbonintensity]-5-fluoro-N2-[1-(methoxycarbonylmethylene)indol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d which 9.22(s, 1H), 8,96(s, 1H), 8,03(d, J=3,9 Hz, 1H), of 7.90-7,72(m, 4H), 7,28-of 7.23(m, 3H), 6,94(d, J=8.7 Hz, 1H), 6,32(d, J=3.0 Hz, 1H), 5,07(s, 2H), 4.53-in(s, 2H), to 3.67(s, 3H), 2,67(d, J=4.5 Hz, 3H); LC/MS: purity: 90%; MS(mass/charge): 514(MH+).++-
645N4-(4-Chloro-3-methoxyphenyl)-5-fluoro-N2-[1-(methoxycarbonylmethylene)indol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.32(s, 1H), 8,96(s, 1H), 8,07(d, J=3.6 Hz, 1H), to 7.84(s, 1H), 7,55-7,47(m, 2H), 7,28-7,17(m, 4H), of 6.29(d, J=3.0 Hz, 1H), to 5.08(s, 2H), to 3.67(s, 3H), of 3.64(s, 3H); LC/MS: purity: 96%; MS(mass/charge): 457(MH+). ++-
646N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(methoxycarbonylmethylene)indol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,18(s, 1H), to 8.94(s, 1H), 8,02(d, J=3.0 Hz, 1H), 7,82-7,76(m, 2H), of 7.70(DD, J=2.1 and 9.0 Hz, 1H), 7,27-7,21(m, 3H), 7,03(d, J=9.0 Hz, 1H), 6,30(d, J=2.7 Hz, 1H), is 5.06(s, 2H), 3,83(s, 3H), 3,66(s, 3H); LC/MS: purity: 98%; MS(mass/charge): 456(MH+).++-
647N4-(3,4-Atlanticcity)-5-fluoro-N2-[1-(methoxycarbonylmethylene)indol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,18(s, 1H), 9,99(s, 1H), 8,16(d, J 4.5 Hz, 1H), 7,74(s, 1H), 7,46-to 7.18(m, 3H), 7,34-to 7.18(m, 3H), 6,83(d, J=8,1 Hz, 1H), 6,46(d, J=3.0 Hz, 1H), 5,20(s, 2H), 4,29(s, 4H), 3,74(s, 3H); LC/MS: purity: 92%; MS(mass/charge): 450(MH+).++-
648N4-[3-Chloro-4-(N-methylamino)carbonintensity]-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 9.25(s, 1H), 9,07(s, 1H), 8,04(d, J=3.6 Hz, 1H), of 7.90-7,83(m, 3H), to 7.77-7,73(m, 1H), 7,55-7,52(m, 1H), 7,39(d, J=9.0 Hz, 1H), 7,32-7,26(m, 1H) 7,16(d, J=3.3 Hz, 1H), 6,91(d, J=9,3 Hz, 1H), 6,33(d, J=3.0 Hz, 1H), to 4.62(s, 4H), to 4.52 (s, 2H), to 2.67 (d, J=4,2 Hz, 3H), 2,58 (d, J=4.5 Hz, 3H); LC/MS: purity: 94%; MS(mass/charge): 513(MH+).++-+
649N4-(3,4-Atlanticcity)-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,06(s, 1H), of 9.02(s, 1H), to 7.99(d, J=3,9 Hz, 1H), 7,88-of 7.82(m, 1H), 7,58(s, 1H), 7,39-7,33(m, 2H), 7,32-7,25(m, 2H), 7,16(d, J=3.3 Hz, 1H), of 6.71(d, J=8.7 Hz, 1H), 6,33(d, J=3.3V Hz, 1H), 4,63(s, 2H), 4,19(s, 4H), 2,58(d, J=4,2 Hz, 3H); LC/MS: purity: 97%; MS(mass/charge): 449(MH+).++-
6505-fluoro-N4-[2-(2-hydroxyethyloxy)pyrid-5-yl]-N2-[1-(N-methylamino)carbonylmethyl-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,26(s, 1H), 8,98(s, 1H), 8,51(s, 1H), 8,07(DD, J=2.4 and 9.0 Hz, 1H), 8,03(d, J=3,9 Hz, 1H), 7,98-a 7.92(m, 1H), 7,87(s, 1H), 7.24 to 7,14(m, 3H), 6,76(d, J=9.0 Hz, 1H), 6,27(d, J=3,0 Hz, 1H), 4,84(t, J=5.4 Hz, 1H), 4.72 in(s, 2H), 4,25 (t, J=5.7 Hz, 2H), 3,71 (kV, J=5.7 Hz, 2H), 2,60 (d, J=4.5 Hz, 3H); LC/MS: purity: 90%; MS(mass/charge): 452(MH+).+
651 N4-(3-Chloro-4-trifloromethyl)-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.55(s, 1H), which is 9.09(s, 1H), 8,15-to 7.99(m, 2H), 8,02-to 7.95(m, 1H), 7,89(DD, J=1.5 and 9.6 Hz, 1H), of 7.75(s, 1H), 7,40(d, J=9.0 Hz, 1H), 7,27-7,21(m, 3H), 6,30(d, J=2.7 Hz, 1H), to 4.73(s, 2H,), 2,61(d, J=4.5 Hz, 3H); LC/MS: purity: 99%; MS(mass/charge): 510(MH+).+
652N4-[3-Chloro-4-(N-methylamino)carbonintensity]-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,88(s, 1H), to 9.70(s, 1H), 8,12-8,03(m, 2H), 7,94-7,87(m, 1H), 7,81(d, J=2.4 Hz, 1H), 7,69-7,63(m, 2H), 7,35-7,27(m, 2H), 7,17(d, J=8.7 Hz, 1H), 6,94(d, J=9.0 Hz, 1H), 6.35mm(d, J=3.0 Hz, 1H), of 4.77(s, 2H), 4,55(s, 2H), 2,66 (d, J=4,8 Hz, 3H), 2,61 (d, J=4,8 Hz, 3H); LC/MS: purity: 97%; MS(mass/charge): 513(MH+).++
653N4-(4-Chloro-3-methoxyphenyl)-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,22(s, 1H), to 9.91(s, 1H), 8,16(d, J=4,8 Hz, 1H), 8,12-with 8.05(m, 1H), 7,70-7,66(m, 1H), 7,52-of 7.48(m, 1H), 7,42(d, J=7.8 Hz, 1H), 7,37-7,28(m, 3H), 7,16-7,10(m, 1H), 6.35mm(d, J=2.7 Hz, 1H), 4,79(s, 2H), 3,63(s, 3H), 2,62(d, J=4.5 Hz, 3H); LC/MS: purity: 97%; MS(mass/who long): 456(MH+). +
654N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.21(s, 1H), 9,94(s, 1H), 8,16-8,03(m, 2H), 7,79-7,74(m, 1H), 7,65-7,58(m, 2H), 7,37-7,30(m, 2H), 7,14(d, J=8,4 Hz, 1H), 7,05(d, J=8.7 Hz, 1H), 6,37(d, J=3.0 Hz, 1H), 4,78(s, 2H,), of 3.84(s, 3H), 2,61(d, J=4.5 Hz, 3H); LC/MS: purity: 97%; MS(mass/charge): 456(MH+).+
655N4-(3,4-Atlanticcity)-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,19(users, 1H), 10,04(users, 1H), 8,12-8,03(m, 2H), 7,66-to 7.61(m, 1H), was 7.36-7,30(m, 2H), 7,27-to 7.09(m, 3H), 6,78(d, J=8,4 Hz, 1H), 6,38(d, J=2.7 Hz, 1H), 4,79(s, 2H), 4,23(s, 4H), 2,61(d, J=4,2 Hz, 3H); LC/MS: purity: 99%; MS(mass/charge): 449(MH+).+
656N4-[3-Chloro-4-(N-methylamino)carbonitril]-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,46(s, 1H), 9,07(s, 1H), 8,24-8,17(m, 1H), 8,11(d, J=3.0 Hz, 1H), 8.0 to 7,94(m, 1H), 7,94-7,86(m, 2H), to 7.77(s, 1H), 7,31-7,22(m, 4H), 6,33(d, J=3.3 Hz, 1H), to 4.73(s, 2H), 2,73(d, J=4,8 Hz, 3H), 2,60(d, J=4,8 Hz, 3H); LC/MS: purity: 99%; MS(mass/charge): 482(MH+).+
6572-Chloro-5-fluoro-N4-(2-methoxyphenyl-5-yl)-N4-methyl-4-pyrimidinamine1H NMR(DMSO-d6): d 8,21(d, J=3.0 Hz, 1H), 8,15(d, J=5.7 Hz, 1H), 7,78(DD, J=2.7 and 8.7 Hz, 1H), 6.87 in(d, J=8.7 Hz, 1H), 3,86(s, 3H), 3,38(s, 3H); LC/MS: purity: 95%; MS(mass/charge): 269(MH+).--
6582-Chloro-N4-(4-chloro-3-triptoreline)-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(DMSO-d6): d of 8.25(d, J=5.4 Hz, 1H), 7,97-7,94(m, 1H), 7,78-7,72(m, 2H), 3.45 points(s, 3H); LC/MS: purity: 96%; MS(mass/charge): 341(MH+).--
6592-Chloro-N4-(4-chloro-3-methoxyphenyl)-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(DMSO-d6): d 8,18(d, J=5,1 Hz, 1H), 7,42(d, J=8.7 Hz, 1H), 7,24(s, 1H), of 6.96(d, J=8.7 Hz, 1H), 3,82(s, 1H), and 3.31(s, 3H); LC/MS: purity: 99%; MS(mass/charge): 303(MH+).-
6602-Chloro-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(DMSO-d6): d to 8.14(d, J=5.4 Hz, 1H), 7,56(d, J=2.7 Hz, 1H), 7,34(DD, J=2.4 and 8.7 Hz, 1H), 7,15(d, J=8,4 Hz, 1H), a 3.87(s, 3H), on 3.36(s, 3H); LC/MS: purity: 96%; MS(mass/charge): 303(MH+).--
6612-Chloro-N4-[3-chloro-4-(N-methylamino)carbonintensity]-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(DMSO-d6): d of 8.15(d, J=5.4 Hz, 1H), 7,94-7,87(m, 1H), 7,58(d, J=2.4 Hz, 1H), 7,32(DD, J=2.4 and 8.7 Hz, 1H), 7,02(d, J=9.0 Hz, 1H), 4,60(s, 2H), on 3.36(s, 3H), 2,66(d, J=4,8 Hz, 3H); LC/MS: purity: 90%; MS(mass/charge): 360(MH+).--
662N4-(3-Chloro-4-trifloromethyl)-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,22(s, 1H), 9,88(s, 1H), they were 8.22(d, J=3,9 Hz, 1H), 8,14(d, J=2.7 Hz, 1H), 8,02-to 7.95(m, 1H), 7,84 for 7.78(m, 1H), 7,49(d, J=8,1 Hz, 1H), 7,45-7,37(m, 2H), 7,27(d, J=2.7 Hz, 1H), 7,27(d, J=2.7 Hz, 1H), 7,18(d, J=8,4 Hz, 1H), 6,41 (d, J=3.3 Hz, 1H), 4,70 (s, 2H), 2,58 (d, J=4.5 Hz, 3H); LC/MS: purity: 91%; MS(mass/charge): 509(MH+).+ +-
663N4-(4-Chloro-3-methoxyphenyl)-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,13(s, 1H), 9,90(s, 1H), 8,10(d, J=4.5 Hz, 1H), to $ 7.91(d, J=3,9 Hz, 1H), 7,49-7,34(m, 4H), of 7.23(d, J=3.3 Hz, 1H), 7,17(d, J=8,4 Hz, 1H), 7,07(d, J=8,4 Hz, 1H), 6,37(d, J=3.0 Hz, 1H), to 4.62(s, 2H), 3,52(s, 3H), of 2.51(d, J=4.5 Hz, 3H); LC/MS: purity: 97%; MS(mass/charge): 456(MH+).+-
664N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.21(s, 1H), 10,04(s, 1H), 8,14(d, J=5,1 Hz, 1H), 7,98-a 7.92(m, 1H), to 7.84(d, J=2.7 Hz, 1H), 7,60(DD, J=2.4 and 8.7 Hz, 1H), 7,51(d, J=8.7 Hz, 1H), 7,39(s, 1H), 7,30(d, J=3.3 Hz, 1H), to 7.15(d, J=7.8 Hz, 1H), 7,01(d, J=9.0 Hz, 1H), gold 6.43 (d, J=3.0 Hz, 1H), 4,70 (s, 2H), 3,82 (s, 3H), 2,58 (d, J=4.5 Hz, 3H); LC/MS: purity: 96%; MS(mass/charge): 455(MH+).++-
665N4-[3-Chloro-4-(N-methylamino)carbonitril]-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,50(s, 1H), 9,19(s, 1H), 8,28 to 8.0(m, 1H), 8,12(d, J=3.3 Hz, 1H), 7,97-to 7.84(m, 3H), 7,53(s, 1H), 7,42(d, J=8.7 Hz, 1H), 7,32-of 7.25(d, J=3.3 Hz, 1H), 6.35mm(d, J=3.0 Hz, 1H), 4,63(s, 2H), 2,74(d, J=4.5 Hz, 3H), 2,58(d, J=4.5 Hz, 3H); LC/MS: purity: 96%; MS(mass/charge): 482(MH+).+-
6662-Chloro-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-4-pyrimidinamine1H NMR(DMSO-d6): d 9,94(s, 1H), 8,28(DD, J=0.6 and 3.6 Hz, 1H), of 7.75(d, J=2.1 Hz, 1H), 7,58(DD, J=2.4 and 8.7 Hz, 1H), 7,16(d, J=8.7 Hz, 1H), 3,84(s, 3H); LC/MS: purity: 96%; MS(mass/charge): 288(M+).--
6675-fluoro-N2-[3-(oxazol-2-yl)phenyl]-N4-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,38(s, 1H), 9.28 are(s, 1H), 8,28(s, 1H), 8,14-8,10(m, 2H), 7,87(d, J=7.2 Hz, 1H), 7,50(d, J=7.5 Hz, 1H), 7,34-7,27(m, 2H), 7,06(s, 2H), 3,70(s, 6H), 3,63(s, 3H); LC/MS: purity: 98%; MS(mass/charge): 438(MH+).+
668N4-(3,4-Atlanticcity)-5-fluoro-N2-(2,3,4-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,10(s, 1H), of 7.96(d, J=3,9 Hz, 1H), of 7.75(s, 1H), 7,50(d, J=8.7 Hz, 1H), 7,26(d, J=2.4 Hz, 1H),7,10(DD, J=2.4 Hz, 1H), 6,74-only 6.64(m, 2H), 4,25-4,18(m, 4H), of 3.77(s, 3H), of 3.75(s, 3H), 3,74(s, 3H); LC/MS: purity: 99%; MS(mass/charge): 429(MH+).+
669N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(2,3,4-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,26(s, 1H), 8,01(d, J=3.6 Hz, 1H), 7,86(s, 1H), 7,81(d, J=2.7 Hz, 1H), 7,54(DD, J=2.4 and 9.0 Hz, 1H), 7,43(d, J=9.0 Hz, 1H), 7,03(d, J=9.0 Hz, 1H), 6,70(d, J=9,3 Hz, 1H), 3,81(, 3H), 3,76(s, 3H), 3,74(s, 3H), of 3.73 (s, 3H); LC/MS: purity: 96%; MS(mass/charge): 435(MH+).-
670N4-(4-Chloro-3-methoxyphenyl)-5-fluoro-N2-(2,3,4-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 816(d, J=4,8 Hz, 1H), 7,56-7,51(m, 1H), was 7.36-7,24(m, 4H), 6,74(d, J=9,3 Hz, 1H), 3,80(s, 3H), 3,74(s, 3H), of 3.73(s, 3H), 3,68(s, 3H); LC/MS: purity: 95%; MS(mass/charge): 436(MH+).-
671N4-(3-Chloro-4-trifloromethyl)-5-fluoro-N2-(2,3,4-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 8.20(d, J=4.5 Hz, 1H), with 8.05(d, J=2.7 Hz, 1H), 7,73-7,66(m, 1H), 7,45(d, J=9.6 Hz, 1H), and 7.4(d, J=8.7 Hz, 1H), 6.75 in(d, J=9.0 Hz, 1H), of 3.78(s, 3H), 3,74(s, 3H), of 3.73(s, 3H); LC/MS: purity: 95%; MS(mass/charge): 490(MH+).+
672N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(2,3,4-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.73(s, 1H), 10,44(s, 1H), 8,21(d, J=4,8 Hz, 1H), 7,43-7,32(m, 1H), 7,27-7,13(m, 2H), 6.89 in(d, J=8,4 Hz, 1H), 6,65(d, J=9.6 Hz, 1H), of 3.77(s, 3H), 3,76(s, 3H), 3,74(s, 3H), 1,41(s, 6H); LC/MS: purity: 98%; MS(mass/charge): 470(MH+).+
673N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine salt benzosulfimide acid1H NMR(DMSO-d6): d 11,14(s, 1H), 9,98(s, 1H), 9,63(s, 1H), 8,17(d, J=3,9 Hz, 1H), 7,62-7,52(m, 3H), of 7.36-7,25(m, 4H), 6.87 in(s, 2H), 3,66(s, 6H), 3,61(s, 3H), USD 1.43(s, 6H).++
674N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine salt methanesulfonic acid1H NMR(DMSO-d6) d 11,13(s, 1H), 9,95(s, 1H), 9,62(s, 1H), 8,18(d, J=3,9 Hz, 1H), 7,56(d, J=9.0 Hz, 1H), 7,31(d, J=8,4 Hz, 1H), to 6.88(s, 2H), 3,66(s, 6H),3,61(s, 3H), of 2.33(s, 3H), USD 1.43(s, 6H).++
675N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR(DMSO-d6): d 11,12(s, 1H), of 9.89(s, 1H), to 9.57(s, 1H), 8,17(d, J=3,9 Hz, 1H), EUR 7.57(d, J=8,4 Hz, 1H), 7,45(d, J=7.8 Hz, 2H), 7,31(d, J=8,4 Hz, 1H), to 7.09(d, J=7.8 Hz, 2H), 6.89 in(s, 2H), 3,66(, 6H), 3,61(s, 3H), of 2.28(s, 3H), USD 1.43(s, 6N).++
676N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine salt 4-hydroxybenzenesulfonic acid1H NMR(DMSO-d6): d 11,12(s, 1H), 9,81(s, 1H), at 9.53(s, 1H), 8,16(d, J=4,2 Hz, 1H), 7,58(d, J=8.1 Hz, 2H), 7,37(d, J=8.1 Hz, 2H), 7,31(d, J=8.7 Hz, 1H), 6.90 to(s, 2H), only 6.64(d, J=8.7 Hz, 2H), 3,66(, 6H), 3,61(s, 3H), USD 1.43(s, 6H).++
677N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimi indilinga salt of 2,4,6-trimethylbenzenesulfonamide acid 1H NMR(DMSO-d6): d 11,10(s, 1H), 9,72(s, 1H), for 9.47(s, 1H), 8,15(d, J=4,2 Hz, 1H), 7,62-7,56(m, 1H), 7,31(d, J=8,1 Hz, 1H), 6,91(s, 2H), 6,72(s, 2H), 3,66(s, 6H), 3,61(s, 3H), 2,48(s, 6H), 2,16(s, 3H), USD 1.43(s, 6H).+
678N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine salt 0.5 pyridine-3-sulfonic acid1H NMR(DMSO-d6): d 11,08(s, 2H), 9,46(s, 2H), of 9.30(s, 2H), 8,91(s, 1H), to 8.70(d, J=5.4 Hz, 1H), of 8.37(DD, J=1.5 and 7.8 Hz, 1H), 8,13(d, J=3,6 Hz, 2H), 7,80-7,74(m, 1H), 7.62mm(d, J=8.1 Hz, 2H), 7,31(d, J=8.1 Hz, 2H), 6,97(s, 4H), 3,66(s, N), 3,60 (C, 6N), USD 1.43 (s, N).++
679N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine salt p-ethylbenzophenone acid1H NMR(DMSO-d6): d 11,08(s, 1H), 9,44(s, 1H), 9,26(s, 1H), 8,13(d, J=3.3 Hz, 1H), 7,63(d, J=8,4 Hz, 1H), 7,47(d, J=8.1 Hz, 2H), 7,31(d, J=8,1 Hz, 1H), 7,12(d, J=7.8 Hz, 2H), 6,97(s, 2H), 3,65(, 6H)and 3.59(s, 3H), 2.57 m(sq, J=7.8 Hz, 2H), 1,42 (C, 6N)and 1.15 (t, J=7.8 Hz, 3H).++
680 N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine salt 0,5 1,2-ethicolegal acid1H NMR(DMSO-d6): d 11,08(s, 2H), 9,54(s, 2H), 9,35(s, 2H), 8,14(d, J=3,9 Hz, 2H), 7,60(d, J=8,4 Hz, 2H), 7,31(d, J=8,4 Hz, 2H), 6,95(s, 4H), 3,66(s, 12H), of 3.60(s, 6H), 2,62(s, 4H), USD 1.43(s, 12H).++
681N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine salt of (1R)-10-camphorsulfonic acid1H NMR(DMSO-d6): d of 11.11(s, 1H), 9,83(s, 1H), 9,54(s, 1H), 8,17(d, J=3,9 Hz, 1H), EUR 7.57(d, J=8.7 Hz, 1H), 7,30(d, J=8,4 Hz, 1H), 6,99(s, 2H), 3,66(s, 6H), 3,61(s, 3H), 2,86(d, J=14,7 Hz, 1H), 2,67(t, J=9.9 Hz, 1H), 2,38(d, J=14,7 Hz, 1H), 2,22 (dt, J=3.6 and is 18.0 Hz, 1H), 1.93 and (t, J=4.5 Hz, 1H), 1,89 is 1.75 (m, 2H), USD 1.43 (s, 6N), 1,30-of 1.23 (m, 2H), only 1.08 (t, J=6,9 Hz, 1H), was 1.04 (s, 3H), 0.74 and (s, 3H).++
682N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine salt of (1S)-10-camphorsulfonic acid1H NMR(DMSO-d6): d 11,08(s, 1H), of 9.55(s, 1H), 9,36(s, 1H), 8,14(d, J=3,9 Hz, 1H), 7,60(d, J=8.7 Hz, 1H), 7,31(d, J=8,4 Hz, 1H), 6,94(s, 2H), 3,66(s, 6), of 3.60(s, 3H), 2,85(d, J=14,7 Hz, 1H), 2,68(t, to 11.4 Hz, 1H), 2,36(d, J=14,7 Hz, 1H), 2,28-2,17 (m, 1H), 1,92 (t, J=4,8 Hz, 1H), 1,89-of 1.74 (m, 2H), USD 1.43 (s, 6N), 1,26 (kV, J=10,8 Hz, 2H), of 1.05 (s, 3H), 0.74 and (with, 3H).++
683N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(N-methylamino)carbonylmethyl-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,04(s, 1H), remaining 9.08-of 8.90(m, 2H), 8,07(d, J=3.3 Hz, 1H), 7,99-7,89(m, 1H), 7,81-of 7.96(m, 1H), 7,70-to 7.64(m, 1H), 7,29-7,20(m, 4H), of 6.29(d, J=3.0 Hz, 1H), to 4.73(s, 2H), 2,61(d, J=4.5 Hz, 3H), of 1.42(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 491(MH+).++
684N2-(4-Chloro-3, 5dimethylphenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR(DMSO-d6): d 11,13(s, 1H), 9,68(s, 1H), 9,46(s, 1H), 8,17(d, J=3.6 Hz, 1H), 7,51-7,35(m, 6H), to 7.09(d, J=8,4 Hz, 2H), 2,28(s, 3H), 2,22(s, 6H), USD 1.43(s, 6H).+
685N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinium is at the cleaners containing hydrochloride salt 1H NMR(DMSO-d6): d to 11.31(s, 1H), of 9.89(s, 1H), to 9.66(s, 1H), 8,18(d, J=4.5 Hz, 1H), 7,55(d, J=8,4 Hz, 1H), 7,30(d, J=8.7 Hz, 1H), 6.89 in(s, 2H), 3,65(s, 6H), 3,61(s, 3H), USD 1.43(s, 6H).++
686N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(3,5-dichloro-4-hydroxyphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,07(s, 1H), to 9.32(s, 1H), 9,27(s, 1H), 8,13(d, J=3.3 Hz, 1H), 7,63(s, 2H), 7,45(d, J=8.7 Hz, 1H), 7,35(d, J=8.7 Hz, 1H), USD 1.43(s, 6H); LC/MS: purity: 92%; MS(mass/charge): 467(MH+).++
687N2,N4-Bis(3-oxo-2,2,4-trimethyl-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,49(users, 2H), 8,18(d, J=3.3 Hz, 1H), to 7.93(d, J=8.7 Hz, 1H), 7,74(d, J=8,4 Hz, 1H), 7,37(d, J=8.7 Hz, 1H), 7,28(d, J=8,4 Hz, 1H), 3,34(s, 3H), of 3.33(s, 3H), of 1.44(s, 6H), of 1.41(s, 6H); LC/MS: purity: 98%; MS(mass/charge): 509(MH+).+
688N2,N4-Bis(2,2-dimethyl-4-carbomethoxy-3-oxo-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d of 9.55(s, 1H), 9,49(s, 1H), 8,19(d, J=2.7 Hz, 1H), of 7.97(d, J=8.7 Hz, 1H), 7,79(d, J=8.7 Hz, 1H), 7,45(d, J=8.7 Hz, 1H), 7,38(d, J=8.7 Hz, 1H), to 4.81(s, 2H), 4,80(s, 2H), to 3.67(s, 3H), 3,66(s, 3H), of 1.48(s, 6H), 1,45(s, 6H); LC/MS: purity: 97%; MS(mass/charge): 625(MH+).-
6895-fluoro-N4-(3-oxo-2,2,4-trimethyl-5-pyrid[1,4]oxazin-6-yl)-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,42(s, 1H), 9,13(s, 1H), 8,14(d, J=3.6 Hz, 1H), 7,80(d, J=8,4 Hz, 1H), 7,32(d, J=8,4 Hz. 1H), 7,03(s, 2H), 3,66(s, 6H), of 3.60(s, 3H), of 1.44(s, 6H); LC/MS: purity: 97%; MS(mass/charge): 485(MH+).+
690N4-(2,2-Dimethyl-4-carbomethoxy-3-oxo-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,46(s, 1H), 9.15, with(s, 1H), 8,15(d, J=3.6 Hz, 1H), 7,86(d, J=8.7 Hz, 1H), 7,37(d, J=8.7 Hz, 1H),? 7.04 baby mortality(s, 2H), 4,80(s, 2H), to 3.67(s, 6H), 3,66(s, 3H), of 3.60(s, 3H), of 1.47(s, 6H); LC/MS: purity: 96%; MS(mass/charge): 543(MH+).+
691N4-(2,2-Dimethyl-4-carb is oxymethyl-3-oxo-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N4-carbomethoxyamino-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,27(s, 1H), they were 8.22(d, J=4,8 Hz, 1H), 7,42(d, J=8,4 Hz, 1H), 6,98(s, 2H), for 6.81(DD, J=3.3 and an 8.4 Hz, 1H), a 4.83(s, 2H), 4,63(s, 2H), and 3.72(s, 6H), 3,63(s, 3H)and 3.59(s, 3H), of 3.57(s, 3H), 1,47(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 615(MH+).+
692N2-[3,5-Dimethoxy-4-(2-(N-morpholino)atilax)phenyl]-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,04(s, 1H), 9,14(s, 1H), which is 9.09(s, 1H), 8,11(d, J=3.6 Hz, 1H), 7,65(d, J=8,4 Hz, 1H), 7,31(d, J=8,4 Hz, 1H), 7,02(s, 2H), a 3.87(t, J=6.0 Hz, 2H), 3,65(s, 6H), to 3.58-of 3.53(m, 4H), 2,58(t, J=6.0 Hz, 2H), 2,47-to 2.42(m, 4H), of 1.42 (s, 6N); LC/MS: purity: 96%; MS(mass/charge): 570(MH+).++
693N2, N4-Bis(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,07(s, 1H), 10,91(s, 1H), 9,27(s, 1H), 9,12(s, 1H), 8,13(d, J=3.3 Hz, 1H), 7,69(d, J=8,4 Hz, 1H), 7,60(d, J=9.0 Hz, 1H), 7,32(d, J=8,4 Hz, 1H), 7,22(d, J=9.0 Hz, 1H), 1,43(, gH), of 1.39(s, 6H); LC/MS: purity: 99%; MS(mass/charge): 481(MH+).+
694 N4-(3-Chloro-4-methoxyphenyl)-N2-(1-ethylindole-5-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,36(s, 1H), of 10.21(s, 1H), 8,24(d, 1H, J=4.9 Hz), 7,92(s, 1H), 7,83(s, 1H), 7,74(d, 1H, J=2.6 Hz), the 7.65(d, 1H, J=9.1 Hz), 7,54(iscd, 1H, J=2.3 and 9.1 Hz), 7,38(DD, 1H, J=1.8 and 9.1 Hz), to 7.09(d, 1H, J=9.1 Hz), 4,40(Qut, 2H, J=7.0 Hz), 3,83(s, 3H), of 1.38(t, 3H, J=7.0 Hz). LC/MS: retention time: of 9.30 min; purity: 97%; MS(mass/charge): 414(MH+).++-
695N4-(3,4-Dichlorophenyl)-N2-(1-ethylindole-5-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,28(s, 1H), 10,02(s, 1H), 8,28(d, 1H, J=4,7 Hz), 8,02(d, 1H, J=2.3 Hz), 7,94(s, 1H), 7,87(s, 1H), of 7.70(s, 1H), 7,66(d, 1H, J=9.1 Hz), 7,52(d, 1H, J=8,8 Hz), 7,42(DD, 1H, J=the 2.3 and 8.8 Hz), to 4.41(Qut, 2H, J=7,0 Hz)to 1.38 (t, 3H, J=7.0 Hz); LC/MS: retention time: 12,41 min; purity: 99%; MS(mass/charge): 418(MH+).--
696N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-N2-(1-ethylindole-5-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,77(s, 1H), accounted for 10.39(s, 1H), of 10.21(s, 1H), they were 8.22(d, 1H, J=5.3 Hz), 7,89(s, 2H), to 7.61(d, 1H, J=8,8 Hz), 7,37(d, 1H, J=8,8 Hz), 7,20(DD, 2H, J=2.3 and 8.2 Hz), for 6.81(d, 1H, J=8,2 Hz), 4,39(Qut, 2H, J=7,0 Hz)to 1.37(s, 6N), of 1.36 (t, 3H, J=7.0 Hz); LC/MS: BP is me holding: 8,77 min; purity: 97%; MS(mass/charge): 448(MH+).++++
697N2-(1-Ethylindole-5-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,42(s, 1H), 10,29(s, 1H), compared to 8.26(d, 1H, J=4.9 Hz), 7,89(s, 2H), 7,63(d, 1H, J=8,8 Hz), 7,44(d, 1H, J=8,2 Hz), 7,37(d, 1H, J=9.0 Hz), 7,31-of 7.23(m, 1H), 7,19(DD, 1H, J=8.8 and 11.8 Hz), to 4.41(Qut, 2H, J=7.0 Hz), 3,60 (s, 3H), of 1.37 (t, 3H, J=7.0 Hz); LC/MS: retention time: a 9.09 min; purity: 98%; MS(mass/charge): 398(MH+).++-
698N4-(3-Chloro-4-methoxyphenyl)-N2-(1-ethylindole-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,44(s, 1H), the 10.40(s, 1H), 8,32(d, 1H, J=4.9 Hz), 7,92(s, 1H), 7,78(ISCT, 2H, J=2,6 Hz), to 7.67(d, 1H, J= 8.5 Hz), 7,58-7,52(dt, 1H, J=2.6 and 9.1 Hz), 7,16(d, 1H, J=8,8 Hz), 7,10(d, 1H, J=9.1 Hz), 4,11(Qut, 2H, J=7.0 Hz), 3,83 (s, 3H), 1,25 (t, 3H, J=7.0 Hz); LC/MS: retention time: 10,83 min; purity: 96%; MS(mass/charge): 414(MH+).++-
699N4-(3,4-Dichlorophenyl)-N2-(1-ethylindole-6-yl)-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,92(s, 1H), 9,78(s, 1H), 8,27(d, 1H, J=4,1 Hz), 8,08(iscd, 1H, J=2.6 Hz), to 7.93(s, 1H), to $ 7.91(s, 1H), 7,76(dt, 1H, J=2.6 and 8.1 Hz), a 7.62(d, 1H, J=8.5 Hz), 7,54(d, 1H, J=8,8 Hz), 7.23 percent(d, 1H, J=8.5 Hz), 4,14(Qut, 2H, J=7,0 Hz)of 1.29 (t, 3H, J=7.0 Hz); LC/MS: retention time: 14,02 min; purity: 98%; MS(mass/charge): 418(MH+).++
700N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-N2-(1-ethylindole-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d is 10.75(s, 1H), 10,18(s, 2H), of 8.25(d, 1H, J=4,7 Hz), 7,94(s, 1H), to 7.84(s, 1H), 7,63(d, 1H, J=8.5 Hz), 7,27-7,17(m, 3H), 6,86(d, 1H, J=8.5 Hz), 4,14(Qut, 2H, J=7,0 Hz)to 1.38(s, 6H), of 1.28(t, 3H, J=7.0 Hz). LC/MS: retention time: 9,07 min; purity: 98%; MS(mass/charge): 448(MH+).+++
701N2-(1-Ethylindole-6-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,18(s, 2H), compared to 8.26(d, 1H, J=4,7 Hz), to 7.93(s, 1H), of 7.90(s, 1H), 7.62mm(d, 1H, J=8.5 Hz), 7,50-7,46(m, 1H), 7,30-7,27(m, 1H), 7,19-7,13(m, 2H), 4.09 to(Qut, 2H, J=7.0 Hz), 3,60(s, 3H), of 1.27(t, 3H, J=7.0 Hz). LC/MS: retention time: 10,82 min; purity: 99%; MS(mass/charge): 397(MH+).++
702N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(1-n-propionate-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d accounted for 10.39(s, 1H), 10,26(s, 1H), compared to 8.26(d, 1H, J=4,7 Hz), 7,92(s, 1H), 7,82(s, 1H), of 7.75(d, 1H, J=2.7 Hz), of 6.66(d, 1H, J=9.1 Hz), 7,54(dt, 1H, J=2.3 and 9.1 Hz), was 7.08(d, 1H, J=9.1 Hz), 4,33(t, 2H, J=7.0 Hz), 3,83(s, 3H), equal to 1.82 (q, 2H, J=7.03 is Hz), 0,81 (t, 3H, J=7.0 Hz); LC/MS: retention time: 10,32 min; purity: 98%; MS(mass/charge): 427(MH+).+
703N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(1-n-propionate-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.21(s, 1H), to 9.93(s, 1H), compared to 8.26(d, 1H, J=4.4 Hz), 8,01(d, 1H, J=2.6 Hz), 7,94(s, 1H), 7,87(s, 1H), 7,69(DD, 1H, J=a 1.8 and 8.8 Hz), the 7.65(d, 1H, J=9.1 Hz), 7,49(d, 1H, J=8,8 Hz), 7,41(DD, 1H, J=9.1 Hz), 4,34(t, 2H, J=7,0 Hz)and 1.83 (Qut, 2H, J=7,0 Hz)of 0.82 (t, 3H, J=7.0 Hz); LC/MS: retention time: 13,49 min; purity: 98%; MS(mass/charge): 432(MH+).+
704N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(1-n-propionate-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d is 10.75(s, 1H), of 10.21(s, 2H), compared to 8.26(d, 1H, J=4.9 Hz), 7,94(s, 1H), 7,83(s, 1H) 7,63(d, 1H, J=8,8 Hz), 7,27-7,17(m, 3H), 6,86(d, 1H, J=8,8 Hz)4,06(t, 2H, J=7.0 Hz), 1,72(Qut, 2H, J=7,0 Hz)to 1.38(s, 6H), of 0.71(t, 3H, J=7.0 Hz); LC/MS: retention time: 8,27 min; purity: 96%; MS(mass/charge): 462(MH+).++
7055-fluoro-N4-(4-fluoro-3-methoxyphenyl)-N2-(1-n-propionate-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,46(s, 1H), 10,35(s, 1H), 8,28(d, 1H, J=4.9 Hz), of 7.90(s,1H), 7,87(s, 1H), 7,63(d, 1H, J=9.1 Hz), the 7.43(DD, 1H, J=2,3 and 8.8 Hz), 7,27-7,22(m, 1H), 7,14(DD, 1H, J=1,8 and 11.1 Hz), 4,34(t, 2H, J=7.0 Hz), 3,60(s, 3H), 1,82 (Qut, 2H, J=7.0 Hz), 0,81 (t, 3H, J=7.0 Hz); LC/MS: retention time: there is a 10.03 min; purity: 99%; MS(mass/charge): 411(MH+).+
706N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(1-n-propionate-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,51(s, 1H), 10,44(s, 1H), with 8.33(d, 1H, J=4.9 Hz), of 7.96(s, 1H), to 7.77(d, 1H, J=2.6 Hz), to 7.67(d, 1H, J=8,8 Hz), 7,55(DD, 1H, J=2,6 and 8.8 Hz), 7,16(DD, 1H, J=2,6 and 8.8 Hz), a 4.03(t, 2H, J=7,0 Hz), 3,83(s, 3H), 1,68 (Qut, 2H, J=7,0 Hz)of 0.68 (t, 3H, J=7.0 Hz); LC/MS: retention time: 11,82 min; purity: 99%; MS(mass/charge): 427(MH+).++
707N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(1-n-propionate-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,15(s, 1H), 10,02(s, 1H), 8.30 to(d, 1H, J=4.4 Hz), of 8.06(d, 1H, J=2.6 Hz), to 7.93(s, 1H), 7,89(s, 1H), 7,73(DD, 1H, J=2.6 and 8.5 Hz), the 7.65(d, 1H, J=8.5 Hz), 7,55(d, 1H, J=8,8 Hz), 7,21(d, 1H, J=8,8 Hz), 4,07(t, 2H, J=7.0 Hz), 1,71 (Qut, 2H, J=7,0 Hz)to 0.72 (t, 3H, J=7.0 Hz); LC/MS: retention time: 14,82 min; purity: 98%; MS(mass/charge): 433(MH+).++
708N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(1-n-propionate-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,77(s, 1H), 10,37(s, 1H), 10,16(s, 1H), 8,21(d, 1H, J=5.3 Hz), 7,89(s, 1H), 7,87(s, 1H),to 7.61(d, 1H, J=8,8 Hz), 7,37(DD, 1H, J=a 1.8 and 8.8 Hz), 7,20(d, 1H, J=8,8 Hz), 8,87(d, 1H, J=8,8 Hz), or 4.31(t, 2H, J=7.0 Hz), 1,81 (Qut, 2H, J=7.0 Hz), 1,36 (C, 6N), of 0.79 (t, 2H, J=7.0 Hz); LC/MS: retention time: becomes 9.97 min; purity: 99%; MS(mass/charge): 462(MH+).++
7095-fluoro-N4-(4-fluoro-3-methoxyphenyl)-N2-(1-n-propionate-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d the 10.40(s, 1H), 10,37(s, 1H), with 8.33(d, 1H, J=5.0 Hz), of 7.96(s,1H), to 7.84(s, 1H), to 7.64(d, 1H, J=8.5 Hz), 7,47(dt, 1H, J=1.8 and 8.5 Hz), 7,26-7,22(m, 2H), 7,15(DD, 1H, J=11.8 and an 8.8 Hz), was 4.02(t, 2H, J=7.0 Hz), 3,55(s, 3H), 1,68 (Qut, 2H, J=7.0 Hz), 0.69 (t, 3H, J=7.0 Hz); LC/MS: retention time: 11,72 min; purity: 100%; MS(mass/charge): 411(MH+).+
710N2-(1-n-Mutilingual-5-yl)-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d the 10.40(s, 1H), 10,27(s, 1H), 7,92(s, 1H), 7,82(s, 1H), of 7.75(d, 1H, J=2.3 Hz), the 7.65(d, 1H, J=9.1 Hz), 7,54(DD, 1H, J=2.3 and 9.1 Hz), 7,39(d, 1H, J=9.1 Hz), to 7.09(d, 1H, J=9.1 Hz), 4,36(t, 2H, J=7,3 Hz), 3,83(s, 3H), of 1.78 (q, 2H, J=7,3 Hz), 1,22 (ICEX, 2H, J=7,3 Hz)0,86 (t, 3H, J=7,3 Hz), LC/MS: retention time: 12,69 min; purity: 99%; MS (mass/charge): 442 (MH+).+
711N2-(1-n-Mutilingual-5-yl)-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,43(s, 1H), and 10.20(s, 1H), 8,32(d, 1H, J=4,7 Hz), 8,00(d, 1H, J=2.3 Hz), 7,95(s, 1H), 7,83(s, 1H), to 7.67(d, 2H, J=8,8 Hz), 7,49(d, 1H, J=8,8 Hz), 7,41(DD, 1H, J=2,3 and 8.8 Hz), to 4.38(t, 2H, J=7,3 Hz), 1,79(square, 2H, J=7,3 Hz), 1,23 (ICEX, 2H, J=7,3 Hz)of 0.87 (t, 3H, J=7,3 Hz), LC/MS: retention time: $ 15.87 with min; purity: 98%; MS (mass/charge): 446 (MH+).+
712N2-(1-n-Mutilingual-5-yl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d is 10.75(s, 1H), 10,28(s, 1H), of 10.05(s, 1H), 8,19(d, 1H, J=4.9 Hz), 7,89(s, 2H), 7,60(d, 1H, J=9.1 Hz), 7,38(d, 1H, J=9.1 Hz), 7,20(DD, 1H, J=1.8 and 9.1 Hz), 7,16(s, 1H), 6,86(d, 1H, J=9.1 Hz), 4,35(t, 2H, J=7,3 Hz), 1.77 in (q, 2H, J=7,3 Hz), 1,36 (c, 6H), 1,20 (ICEX, 2H, J=7,3 Hz)0,86 (t, 3H, J=7,3 Hz), LC/MS: retention time: 11,06 min; purity: 97%; MS (mass/charge): 476 (MH+).++
713N2-(1-n-Mutilingual-5-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,42(s, 1H), 10,29(s, 1H), 8,27(d, 1H, J=4.9 Hz), 7,89(s, 1H), 7,87(s, 1H), 7,63(d, 1H, J=8,8 Hz), the 7.43(DD, 1H, J=2,3 and 8.8 Hz), was 7.36(DD, 1H, J=1.8 and 9.1 Hz), 7,28-of 7.23(m, 1H), 7,13(DD, 1H, J=11.3 and 9.1 Hz), 4,37 (t, 2H, J=7,3 Hz), 3,60 (c, 3H), of 1.78 (q, 2H, J=7,3 Hz), 1,22 (ICEX, 2H, J=7,3 Hz)0,86 (t, 3H, J=7,3 Hz), LC/MS: retention time: 12,60 min; purity: 99%; MS (mass/charge): 426 (MH+).++
714N2-(1-n-Mutilingual-6-yl)-N4-(3-chloro-4-methoxyp the Nile)-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 10,27(s, 2H), 8,30(d, 1H, J=4,7 Hz), 7,94(s, 1H), 7,82(s, 1H), to 7.77(d, 1H, J=2.6 Hz), the 7.65(d, 1H, J=8,8 Hz), 7,56(DD, 1H, J=2,6 and 8.8 Hz), 7,16(d, 1H, J=8,8 Hz), 7,11(d, 1H, J=8,8 Hz)4,06(t, 2H, J=7,3 Hz), 3,83 (c, 3H), 1,64 (q, 2H, J=7,3 Hz)1,08 (ICEX, 2H, J=7,3 Hz)to 0.78 (t, 3H, J=7,3 Hz), LC/MS: retention time: 14,10 min; purity: 96%; MS (mass/charge): 442 (MH+).+
715N2-(1-n-Mutilingual-6-yl)-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.21(s, 1H), to 10.09(s, 1H), 8,32(d, 1H, J=4.4 Hz), with 8.05(d, 1H, J=2.3 Hz), 7,94(s, 1H), 7,86(s, 1H), 7,72(d, 1H, J=8,8 Hz), 7,66(d, 1H, J=8,8 Hz), 7,55(d, 1H, J=8,8 Hz), 7,20(d, 1H, J=8,8 Hz), 4,11(t, 2H, J=7,3 Hz)of 1.66 (q, 2H, J=7,3 Hz), 1,12 (ICEX, 2H, J=7,3 Hz)of 0.79 (t, 3H, J=7,3 Hz), LC/MS: retention time: 16,86 min; purity: 96%; MS (mass/charge): 446 (MH+).+
716N2-(1-n-Mutilingual-6-yl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,77(s, 1H), the 10.40(s, 1H), 10,36(s, 1H), 8,29(d, 1H, J=4.9 Hz), 7,94(s, 1H), 7,81(s, 1H), 7.62mm(d, 1H, J=8,8 Hz), 7.23 percent(s, 2H), 7,18(d, 1H, J=8,8 Hz), 6,85(d, 1H, J=8,8 Hz), 4,10(t, 2H, J=7,3 Hz), 1,67(square, 2H, J=7,3 Hz), 1,38 (c, 6H), 1,09 (W.the CEN, J=2H, J=7,3 Hz)to 0.78 (t, 3H, J=7,3 Hz), LC/MS: retention time: 12,49 min; purity: 96%; MS (mass/charge): 476 (MH+)++
717N2-(1-n-Mutilingual-6-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,42(s, 1H), 10,37(s, 1H), with 8.33(d, 1H, J=4,7 Hz), of 7.96(s, 1H), to 7.84(s, 1H), to 7.64(d, 1H, J=8,8 Hz), 7,50-7,46(m, 1H), 7,27-7,22(m, 1H), 7,16(INM. t, 1H, J=11.8 and an 8.8 Hz), 4,06(t, 2H, J=7,3 Hz), of 3.54(s, 3H), 1,65(square, 2H, J=7,3 Hz)1,08 (ICEX, 2H, J=7,3 Hz)to 0.78 (t, 3H, J=7,3 Hz), LC/MS: retention time: 14,23 min; purity: 97%; MS (mass/charge): 425 (MH+).+
718N4-(3-Chloro-4-methoxyphenyl)-N2-[1-(cyclohexylmethyl)indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,19(s, 1H), there is a 10.03(s, 1H), they were 8.22(d, 1H, J=4.9 Hz), of 7.90(s, 1H), to 7.84(s, 1H), 7,76(d, 1H, J=2.6 Hz), a 7.62(d, 1H, J=9.1 Hz), 7,56(DD, 1H, J=2.6 and 9.1 Hz), 7,39(DD, 1H, J=1.8 and 9.1 Hz), to 7.09(d, 1H, J=9.1 Hz), 4,20 (d, 2H, J=7.0 Hz), 3,83 (c, 3H), 1,89 is 1.86 (m, 3H), 1,60 (users, 3H), 1,48-1,44 (users, 2H), 1,13-to 0.96 (m, 5H), LC/MS: retention time: 13,78 min; purity: 98%; MS (mass/charge): 481 (MH+).+
719N2-[1-(Cyclohexylmethyl)indazol-5-yl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d RS 9.69(s, 1H), 9,38(s, 1H), 8,17(d, 1H, J=3.8 Hz), 8,07(iscd, 1H, J=2.6 Hz), 7,92(s, 1H), 7,88(s, 1H), 7,78(d, 1H, J=8,8 Hz), 7,58(d, 1H, J=9.1 Hz), 7,49-7,44(m, 2H), 4,19(d, 2H, J=7,3 Hz), 1,91-of 1.84(m, 1H), 1,62(m, 3H), 1,49-of 1.45 (m, 2H), 1,15-to 0.96 (m, 5H), LC/MS: retention time: 17,23 min; purity: 96%; MS (mass/charge): 485 (MH+).+
720N2-[1-(Cyclohexylmethyl)indazol-5-yl]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H of 7.90(s, 1H), to 7.84(s, 1H), 7.62mm(d, 1H, J=9.1 Hz), 7,37(DD, 1H, J=2,3 and 8.8 Hz), 7.23 percent(DD, 1H, J=2.3 and 9.1 Hz), 7,17(s, 1H), at 6.84(d, 1H, J=9.1 Hz), 4,19(d, 2H, J=7,3 Hz), 1,91-of 1.84(m, 1H), 1,62(users, 3H), 1,47-to 1.38(m, 2H), 1,36(s, 6H), 1,13-to 0.96 (m, 5H), LC/MS: retention time: 11,95 min; purity: 96%; MS (mass/charge): 516 (MH+).+
721N2-[1-(Cyclohexylmethyl)indazol-5-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,31(s, 1H), 10,13(s, 1H), of 8.25(d, 1H, J=4.9 Hz), 7,89(s, 1H), 7,87(s, 1H), 7.62mm(d, 1H, J=8,8 Hz) the 7.43(DD, 1H, J=2,6 and 8.8 Hz), was 7.36(DD, 1H, J=1.8 and 9.1 Hz), 7,29-of 7.25(s, 1H), 7,12(DD, 1H, J=8,8 and 11.4 Hz), is 4.21 (d, 2H, J=7,3 Hz), 3,61 (c, 3H), 1,91-of 1.84 (m, 1H), 1,62 (user. c, 3H), 1,48-of 1.44 (m, 2H), 1,16-to 0.96 (m, 5H), LC/MS: retention time: 13,82 min; purity: 98%; MS (mass/charge): 465 (MH+).+
722N4-(3-Chloro-4-methoxyphenyl)-N2-[1-(cyclohexylmethyl)indazol-6-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,12(s, 2H), compared to 8.26(d, 1H, J=4,7 Hz), to 7.93(s, 1H), a 7.85(s, 1H), 7,78(d, 1H, J=2.6 Hz), 7,63(d, 1H, J=8,8 Hz), 7,58(DD, 1H, J=2,6 and 8.8 Hz), 7,19(d, 1H, J=8,8 Hz), 7,11(d, 1H, J=8,8 Hz), 3,90(d, 2H, J=7,3 Hz), 3,82 (c, 3H), 1,74-1,71 (m, 1H), 1,53 (user. c, 3H), of 1.37 and 1.33 (m, 2H), 1,08-of 1.02 (m, 3H), 0,82-0,78 (m, 2H), LC/MS: retention time: 15,24 min; purity: 91%; MS (mass/charge): 481 (MH+).++
723N2-[1-(Cyclohexylmethyl)indazol-6-yl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.05(s, 1H), to 9.91(s, 1H), 8,29(d, 1H, J=4,1 Hz), with 8.05(d, 1H, J=2.3 Hz), 7,92(s, 1H), of 7.90(s, 1H), 7,73(DD, 1H, J=2,3 and 8.8 Hz), 7,63(d, 1H, J=8,8 Hz), 7,54(d, 1H, J=8,8 Hz), 7,21(d, 1H, J=8,8 Hz), 3,93(d, 2H, J=7,3 Hz), 1,78-of 1.74 (m, 1H), and 1.54 (user. c, 3H), of 1.40 and 1.35 (m, 2H), 1,13-of 1.03 (m, 3H), 0.88 to 0,81 (m, 2H), LC/MS: retention time: 17,78 min; purity: 91%; MS (mass/C is a number): 485 (MH+). -
724N2-[1-(Cyclohexylmethyl)indazol-6-yl]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.73(s, 1H), 10,07(s, 1H), 10,01(s, 1H), they were 8.22(d, 1H, J=4,7 Hz), to $ 7.91(s, 1H), 7,86(s, 1H), 7,60(d,1H, J=8,8 Hz), 7,26(DD, 1H, J=2.3 and 8.5 Hz), 7,22-7,19(ISCM, 2H), 6,85(d, 1H, J=8,5 Hz), 3,93(d, 2H, J=7,3 Hz), 1,78-175 (m, 1H), 1,52 (user. c, 3H), 1,38 (c, 6H), 1,36-of 1.32 (m, 2H), 1,09-of 1.03 (m, 3H), 0,88-0,82 (m, 2H), LC/MS: retention time: 13,52 min; purity: 95%; MS (mass/charge): 516 (MH+).+
725N2-[1-(Cyclohexylmethyl)indazol-6-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,24(s, 2H), 8,29(d, 1H, J=4,7 Hz), 7,95(s, 1H), 7,86(s, 1H), 7,63(d, 1H, J=8,8 Hz), 7,49(DD, 1H, J=2,3 and 8.8 Hz), 7,28-7,24(m, 1H), 7,19 for 7.12(m, 2H), 3,91(d, 2H, J=7,3 Hz), 3,55(s, 3H), 1,75-of 1.73(m, 1H), and 1.54(user. c, 3H), of 1.37 and 1.33 (m, 2H), 1,09-of 1.03 (m, 3H), 0,84-of 0.79 (m, 2H), LC/MS: retention time: 15,18 min; purity: 96%; MS (mass/charge): 465 (MH+).+
726N4-(3-Chloro-4-meth is xifei)-N2-[1-(cyclobutylmethyl)indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d the 10.40(s, 1H), 10,26(s, 1H), compared to 8.26(d, 1H, J=5.3 Hz), to $ 7.91(s, 1H), 7,81(s, 1H), of 7.75(d, 1H, J=2.6 Hz), to 7.68(d, 1H, J=9.1 Hz), 7,55(DD, 1H, J=2.6 and a 2.6 and 8.8 Hz), 7,38(d, 1H, J=8,8 Hz), to 7.09(d, 1H, J=9.1 Hz), 4,39(d, 2H, J=7.0 Hz), 3,83 (c, 3H), 2,80 (m, 1H), 1,94-of 1.74 (m, 6H), LC/MS: retention time: 12,08 min; purity: 99%; MS (mass/charge): 455 (MH+).+
727N2-[1-(Cyclobutylmethyl)indazol-5-yl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,32(s, 1H), 10,06(s, 1H), 8,29(d, 1H, J=4,7 Hz), 8,00(s, 1H), to 7.93(s, 1H), to 7.84(s, 1H), 7,68(d, 2H, J=8,8 Hz), 7,49(d, 1H, J=8,8 Hz), 7,41(d, 1H, J=8,8 Hz), and 4.40(d, 2H), 2,86 was 2.76(m, 1H), 1,96 is 1.75(m, 6H). LC/MS: retention time: 15,32 min; purity: 98%; MS (mass/charge): 458 (MH+).+
728N2-[1-(Cyclobutylmethyl)indazol-5-yl]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,79(s, 1H), the 10.40(s, 1H), of 10.25(s, 1H), 8,23(d, 1H, J=4.9 Hz), 7,88(s, 1H), 7,86(s, 1H), to 7.64(d, 1H, J=8,8 Hz), 7,37(d, 1H, J=9.1 Hz), 7,21(s, 1H), 7,18(s, 1H), 6,86(d, 1H, J=9.1 Hz), 4,37(d, 1H, J=7,0 Hz), 2,83-to 2.74 (m, 1H), 1.93 and is 1.70 (m, 6H), 1,36 (c, 6H), LC/MS: retention time: 10,57 min; purity: 97%; MS (mass/charge): 488 (H+). +
729N2-[1-(Cyclobutylmethyl)indazol-5-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,48(s, 1H), 10,36(s, 1H), 8,29(d, 1H, J=5.3 Hz), 7,88(s, 1H), 7,86(s, 1H), to 7.67(d, 1H, J=8.0 Hz), the 7.43(DD, 1H, J=2.3 and 8.0 Hz), 7,35(DD, 1H, J=a 1.8 and 8.8 Hz), 7,26-of 7.23(m, 1H), 7,14(DD, 1H, J=9.1 and 11.8 Hz), and 4.40 (d, 2H, J=7.0 Hz), 3,60 (c, 3H), 1,95-1,71 (m, 6H), LC/MS: retention time: 12,16 min; purity: 99%; MS (mass/charge): 437 (MH+).+
730N4-(3-Chloro-4-methoxyphenyl)-N2-[1-(cyclobutylmethyl)indazol-6-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,35(s, 2H), 8,31(d, 1H, J=4,7 Hz), 7,94(s, 1H), 7,86(s, 1H), 7,78(d, 1H, J=2.3 Hz), 7,66(d, 1H, J=8,8 Hz), EUR 7.57(DD, 1H, J=2,3 and 8.8 Hz), 7,16(d, 1H, J=8,8 Hz), 7,12(d, 1H, J=8,8 Hz), 4.09 to(d, 2H, J=7,3 Hz), 3,83 (c, 3H), 2,69 at 2.59 (m, 1H), 1,86-of 1.56 (m, 6H), LC/MS: retention time: 13.56MHz min; purity: 97%; MS (mass/charge): 454 (MH+).+
731N2-[1-(Cyclobutylmethyl)indazol-6-yl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine/td> 1H NMR(DMSO-d6): d 10,27(s, 1H), 10,16(s, 1H), 8.30 to(d, 1H, J=4.4 Hz), to 7.99(d, 1H, J=2.3 Hz), 7,88(s, 1H), a 7.85(s, 1H), to 7.67(DD, 1H, J=2,3 and 8.8 Hz), 7,60(d, 1H, J=8,8 Hz), 7,51(d, 1H, J=8,8 Hz), 7,13(d, 1H, J=8,8 Hz), 4,07(d, 2H, J=7.0 Hz), 2,66-of 2.56 (m, 1H), 1,83-of 1.56 (m, 6H), LC/MS: retention time: 16,25 min; purity: 96%; MS (mass/charge): 458 (MH+).+
732N2-[1-(Cyclobutylmethyl)indazol-6-yl]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,81(s, 1H), 10,63(s, 1H), 10,55(s, 1H), with 8.33(d, 1H, J=5.3 Hz), 7,94(s, 1H), 7,81(s, 1H), to 7.64(d, 1H, J=8,8 Hz), 7.24 to 7,21(m, 2H), 7,17(d, 1H, J=8.5 Hz), 6,86(d, 1H, J=8,5 Hz), 4,12(d, 2H, J=7.0 Hz), 2.71 to 2,61(m, 1H), 1.85 to to 1.59 (m, 6H), 1,38 (c, 6H), LC/MS: retention time: 12,01 min; purity: 97%; MS (mass/charge): 488 (MH+).+
733N2-[1-(Cyclobutylmethyl)indazol-6-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,67(s, 1H), of 10.58(s, 1H), scored 8.38(d, 1H, J=5.3 Hz), of 7.96(s, 1H), a 7.85(s, 1H), 7,66(d, 1H, J=8.5 Hz), of 7.48(DD, 1H, J=2.3 and 8.5 Hz), 7.23 percent-7,11(m, 3H), 4,07(d, 2H, J=7.0 Hz), 3,51(s, 3H), 2,67-to 2.57(m, 6H). LC/MS: retention time: 13,67 min; purity: 98%; MS (mass/charge): 439 (MH+). +
734N4-(3-Chloro-4-methoxyphenyl)-N2-[1-(cyclopropylmethyl)indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.05(s, 1H), to 9.91(s, 1H), 8,31(d, 1H, J=5,2 Hz), of 7.96(s, 1H), 7,87(s, 1H), 7,80(s, 1H), 7,72(d, 1H, J=8,8 Hz), 7,60(d, 1H, J=8,8 Hz), the 7.43(d, 1H, J=9.1 Hz), 7,14(d, 1H, J=8,8 Hz), or 4.31(d, 2H, J=7.0 Hz), 3,48(s, 3H), of 1.33 (m, 1H), 0,58-0,40 (m, 4H), LC/MS: retention time: 13,98 min; purity: 98%; MS (mass/charge): 439 (MH+).+
735N2-[1-(Cyclopropylmethyl)indazol-5-yl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d accounted for 10.39(s, 1H), 10,14(s, 1H), 8,31(d, 1H, J=4,7 Hz), with 8.05(d, 1H, J=2.3 Hz), 7,98(s, 1H), 7,89(s, 1H), 7,73(d, 1H, J=9.1 Hz), 7,54(d, 1H, J=8,8 Hz), was 7.45(DD, 1H, J=2,3 and 8.8 Hz), 4,32(d, 2H, J=7.0 Hz), 1,34-1,24(m, 1H), 0,54 to 0.44 (m, 4H), LC/MS: retention time: 13,89 min; purity: 96%; MS (mass/charge): 444 (MH+).+
736N2-[1-(Cyclopropylmethyl)indazol-5-yl]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1 H NMR(DMSO-d6): d 10,85(s, 1H), 10,46(s, 1H), 10,29(s, 1H), 8,23(d, 1H, J=5.3 Hz), 7,95(s, 1H), 7,94(s, 1H0, 7,71(d, 1H, J=9.1 Hz), 7,42(DD, 1H, J=2.3 and 9.1 Hz), 7,27(d, 1H, J=8.5 Hz), 7,25(s, 1H), to 6.95(d, 1H, J=8.5 Hz), 4,32(d, 2H, J=7.0 Hz), 1,38 (c, 6H), 1,34-1,24 (m, 1H), 0,54 to 0.44 (m, 4H), LC/MS: retention time: 9,65 min; purity: 96%; MS (mass/charge): 474 (MH+).++
737N2-[1-(Cyclopropylmethyl)indazol-5-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,43(s, 1H), 10,27(s, 1H), 8,31(d, 1H, J=4.3 Hz), 7,95(s, 1H), 7,94(s, 1H), 7,71(d, 1H, J=9.1 Hz), of 7.48(DD, 1H, J=2,3 and 8.8 Hz), 7,41(DD, 1H, J=2.3 and 9.1 Hz), 7,31-7,29(m, 1H), 7,30(DD, 1H, J=8,8 and 11.1 Hz), 4,32 (d, 2H, J=7.0 Hz), 3,65 (c, 3H), 1,33-1,17 (m, 1H), 0.55 to 0,46 (m, 4H), LC/MS: retention time: br11.01 min; purity: 98%; MS (mass/charge): 423 (MH+).+
738N4-(3-Chloro-4-methoxyphenyl)-N2-[1-(cyclopropylmethyl)indazol-6-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,28(s, 2H), 8,31(d, 1H, J=4.3 Hz), 7,95(s, 1H), of 7.96(s, 2H), 7,87(s, 1H), 7,79(d, 1H, J=2.6 Hz), 7,69(d, 1H, J=8,8 Hz), 7,58(DD, 1H, J=2.6 and 9.1 Hz), 7,19(DD, 1H, J=a 1.8 and 8.8 Hz), 7,11(d, 1H, J=9.1 Hz), 4,32(d, 2H, J=6,7 Hz), 3,84 (c, 3H), 1,33-1,17 (m, 1H), 0.55 to 0,46 (m, 4H), LC/MS: retention time: 12,54 min; purity: 8%; MS (mass/charge): 440 (MH+).+
739N2-[1-(Cyclopropylmethyl)indazol-6-yl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.21(s, 1H), 10,10(s, 1H), 8,32(d, 1H, J=4.3 Hz), of 8.04(d, 1H, J=2.6 Hz), to 7.93(s, 1H), to $ 7.91(s, 1H), 7,71(DD, 1H, J=2,6 and 8.8 Hz), the 7.65(d, 1H, J=8,8 Hz), 7,54(d, 1H, J=8,8 Hz), 7,20(d, 1H, J=8,8 Hz), 4,32(d, 2H, J=6,7 Hz), 1,33-1,17 (m, 1H), 0.55 to 0,46 (m, 4H), LC/MS: retention time: 15,18 min; purity: 95%; MS (mass/charge): 444 (MH+).+
740N2-[1-(Cyclopropylmethyl)indazol-6-yl]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d was 10.82(s, 1H), 10,22(s, 1H), 10,16(s, 1H), 8,31(d, 1H, J=4,7 Hz), 8,00(d, 1H, J=0.8 Hz), of 7.97(s, 1H), 7,34(d, 1H, J=8,8 Hz), 7,35-7,27(m, 3H), 6,92(d, 1H, J=8.5 Hz), 4,32(d, 2H, J=7,0 Hz)of 1.36(s, 6H), 1,33-1,17(m, 1H), 0.55 to 0.45 in (m, 2H), 0,35-0,30 (m, 2H), LC/MS: retention time: of 10.93 min; purity: 96%; MS (mass/charge): 474 (MH+).++
741N2-[1-(Cyclopropylmethyl)indazol-6-yl)-5-fluoro-N4-(4-f the PR-3-methoxyphenyl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 10,23(s, 2H), 8,31(d, 1H, J=4.9 Hz), 7,95(s, 1H), to $ 7.91(s, 1H), 7,65(d, 1H, J=8,8 Hz), of 7.48(DD, 1H, J=2,3 and 8.8 Hz), 7,29-7,24(m, 1H), 7,20-7,13(m, 3H), 4.09 to(d, 2H, J=6,7 Hz), 3,65(s, 3H), 1,33-1,17(m, 1H), 0.55 to 0,46 (m, 2H), 0,35-0,30 (m, 2H), LC/MS: retention time: 12,54 min; purity: 98%; MS (mass/charge): 423 (MH+).+
742N4-(3-Chloro-4-methoxyphenyl)-N2-(1-cyclohexylidene-5-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,35(s, 1H), and 10.20(s, 1H), 8,24(d, 1H, J=5.3 Hz), 7,92(s, 1H), 7,81(s, 1H), 7,74(d, 1H, J=2.6 Hz), 7,71(d, 1H, J=8.1 Hz), 7,55(DD, 1H, J=2,6 and 8.8 Hz), was 7.36(DD, 1H, J=a 1.8 and 8.8 Hz), to 7.09(d, 1H, J=8.1 Hz), 4,56-a 4.53 (m, 1H), 3,82 (c, 3H), 1.91 a-to 1.82 (m, 6H), 1,72 by 1.68 (m, 1H), 1,51 -1,46 (m, 2H), 1,31-of 1.23 (m, 1H), LC/MS: retention time: 13,04 min; purity: 98%; MS (mass/charge): 467 (MH+).++
743N2-(1-Cyclohexylidene-5-yl)-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,26(s, 1H), 9,99(s, 1H), 8,23(d, 1H, J=4.9 Hz), of 7.96(s, 1H), 7,89(s, 1H), 7,80(s, 1H), 7,66(d, 1H, J=8.1 Hz), to 7.61(ISCS, 1H), 7,45(d, 1H, J=9.1 Hz), 7,34(d, 1H, J=9.1 Hz), 4,53 figure-4.49(m, 1H), 1,87-of 1.78(m, 6H), 1,67-to 1.63 (m, 1H), 1,46-of 1.42(m, 2H), 1,27-of 1.18 (m, 1H), LC/MS: retention time: 16,43 min; purity: 7%; MS (mass/charge): 472 (MH+).+
744N2-(1-Cyclohexylidene-5-yl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,80(s, 1H), 10,36(s, 1H), 10,15(s, 1H), 8,21(d, 1H, J=4.9 Hz), 7,89(s, 1H), 7,86(s, 1H), to 7.64(d, 1H, J=9.4 Hz), was 7.36(DD, 1H, J=2,3 and 8.8 Hz), 7,18(d, 1H, J=2.3 Hz), 6,86(d, 1H, J=9.4 Hz), 4.53-in figure-4.49(m, 1H), 1,89-to 1.82 (m, 6H), 1,72 by 1.68 (m, 1H), 1,52 was 1.43 (m, 2H), 1,36 (c, 6H), 1,29 is 1.23 (m, 1H), LC/MS: retention time: 11,44 min; purity: 96%; MS (mass/charge): 502 (MH+).++
745N2-(1-Cyclohexylidene-5-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,26(s, 1H), 10,07(s, 1H), they were 8.22(d, 1H, J=5.0 Hz), of 7.90(s, 1H), 7,89(s, 1H), to 7.67(d, 1H, J=8,8 Hz), 7,44(DD, 1H, J=8.5 Hz), 7,34(DD, 1H, J=a 1.8 and 8.8 Hz), 7,28-7,24(m, 1H), 7,15(DD, 1H, J=8,8 and 11.1 Hz), 4.53-in-4, 49 (m, 1H), 3,59 (c, 3H), 1,91-of 1.84 (m, 6H), 1,72 by 1.68 (m, 1H), 1,52 was 1.43 (m, 2H), 1,31-of 1.23 (m, 1H), LC/MS: retention time: 13,11 min; purity: 98%; MS (mass/charge): 451 (MH+).+
7461H NMR(DMSO-d6): d of 10.21(s, 1H), 10,19(s, 1H), 8,28(d, 1H, J=4.9 Hz), 7,95(s, 1H), 7,86(d, 1H, J=2.6 Hz), to 7.84(s, 1H), 7,66(d, 1H, J=8.5 Hz), to 7.59(DD, 1H, J=2.6 and 9.1 Hz), 7,21(DD, 1H, J=1.8 and 8.5 Hz), 7,06(d, 1H, J=9.1 Hz), 4,19-4,06 (m, 1H), 3,80 (c, 3H), 1,83-of 1.74 (m, 6H), 1,65-of 1.62 (m, 1H), 1,29-of 1.15 (m, 3H), LC/MS: retention time: 14,39 min; purity: 97%; MS (mass/charge): 465 (MH+).+
747N2-(1-Cyclohexylidene-6-yl)-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.05(s, 1H), 9,88(s, 1H), 8,29(d, 1H, J=4.9 Hz), 8,11(d, 1H, J=2.6 Hz), to 7.93(s, 1H), 7,92(s, 1H), 7,78(DD, 1H, J=2,6 and 8.8 Hz), to 7.64(d, 1H, J=8.5 Hz), 7,51(d, 1H, J=8,8 Hz), 7,22(DD, 1H, J=1.7 and 8.5 Hz), 4,19-4,06 (m, 1H), 1.85 to to 1.77 (m, 6H), 1,65-of 1.62 (m, 1H), 1,29 is 1.13 (m, 3H), LC/MS: retention time: 17,10 min; purity: 94%; MS (mass/charge): 472 (MH+).+
748N2-(1-Cyclohexylidene-6-yl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.76(s, 1H), of 10.25(s, 1H), 10,18(s, 1H), 8,24(d, 1H, J=4.9 Hz), 7,94(s, 1H), 7,83(s, 1H), 7,63(d, 1H, J=8.5 Hz), 7,31-7,22(m, 3H), to 6.80(d, 1H, J=8.5 Hz), 4,2-4,12(m, 1H), 1.85 to to 1.77(m, 6H), 1,65-of 1.62(m, 1H), 1,38(s, 6H), 1,29 is 1.13 (m, 3H), LC/MS: retention time: 12,78 min; purity: 94%; MS (mass/charge): 502 (MH+).+
749N2-(1-Cyclohexylidene-6-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,02(s, 1H), 9,95(s, 1H), compared to 8.26(d, 1H, J=4.3 Hz), to 7.93(s, 2H), 7,83(s, 1H), 7,63(d, 1H, J=8,8 Hz), 7,55(DD, 1H, J=2,6 and 8.8 Hz), 7,31-7,28(m, 1H), 7,18(d, 1H, J=8,8 Hz), 7,12(DD, 1H, J=8,8 and 11.4 Hz), 4,11-4,00 (m, 1H), 3,49 (c, 3H), 1,82 is 1.75 (m, 6H), 1,65-of 1.62 (m, 1H), 1,29 is 1.13 (m, 3H), LC/MS: retention time: 14,35 min; purity: 94%; MS (mass/charge): 452 (MH+).+
750N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(3-methylindol-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 12,23(s, 1H), at 9.53(s, 1H), 9,36(s, 1H), 8,14(d, 1H, J=3.5 Hz), 8,10(d, 1H, J=2.7 Hz), 7,88(s, 1H), 7,86(DD, 1H, J=2.7 and 8.8 Hz), 7,47(d, 2H, J=8,8 Hz), 7,16(DD, 1H, J=a 1.8 and 8.8 Hz), a 2.36(s, 3H). LC/MS: retention time: br12.62 min; purity: 94%; MS (mass/charge): 404 (MH+).++
751N4-(2,2-Dimethyl--oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(3-methylindol-6-yl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d to 10.62(s, 1H), 9,63(s, 1H), 9,44(s, 1H), 8,13(d, 1H, J=41 Hz), to 7.84(s, 1H), 7,50(d, 1H, J=8,8 Hz), was 7.36(DD, 1H, J=2.3 and 8.5 Hz), 7,31(d, 1H, J=2.3 Hz), 7,24(DD, 1H, J=1.8 and 8,8 Hz), 6.89 in(d, 1H, J=8.5 Hz), 2,41(c, 3H), 1.39 in (c, 6H), LC/MS: retention time: 8,78 min; purity: 92%; MS (mass/charge): 434 (MH+).++
752N4-(3-Chloro-4-methoxyphenyl)-N2-(1,3-dimethylindole-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,49(s, 1H), 10,43(s, 1H), with 8.33(d, 1H, J=5.3 Hz), to 7.77(d, 1H, J=2.6 Hz), to 7.67(d, 1H, J=1.2 Hz), a 7.62(d, 1H, J=8,8 Hz), 7,55(DD, 1H, J=2,6 and 8.8 Hz), 7,10(d, 1H, J=8,8 Hz), to 7.09(d, 1H, J=8,8 Hz), 3,83(s, 3H), 3,67 (c, 3H), 2,41 (c, 3H), LC/MS: retention time: 11,19 min; purity: 94%; MS (mass/charge): 413 (MH+).++
753N4-(3,4-Dichlorophenyl)-N2-(1,3-dimethylindole-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,65(s, 1H), 9,50(s, 1H), they were 8.22(d, 1H, J=3,5H), to 8.12(d, 1H, J=2.3 Hz), to $ 7.91(d, 1H, J=1.8 Hz), 7,79(DD, 1H, J=2,3 and 8.8 Hz), 7,52(DD, 2H, J=2.3 and 8,8gts), 7,18(DD, 1H, J=1.8 and 8,8 Hz), of 3.69(s, 3H), 2,39(s, 3H), LC/MS: retention time: 13,96 min; purity: 97%; MS (mass/charge): 418 (MH+).++
754N2-(1,3-Dimethylindole-6-yl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.72(s, 1H), of 10.25(s, 2H), compared to 8.26(d, 1H, J=4.9 Hz), 7,72(s, 1H), EUR 7.57(d, 1H, J=8.5 Hz), 7,25(DD, 1H, J=2.3 and 8.5 Hz), 7,22(ISCS, 1H), 7,14(DD, 1H, J=2.3 and 8.5 Hz), 6.87 in(d, 1H, J=8,5 Hz), 3,37(s, 3H), 2.40 a(s, 3H), 1,38 (c, 6H), LC/MS: retention time: 9,77 min; purity: 94%; MS (mass/charge): 448 (MH+).+++
755N2-(1,3-Dimethylindole-6-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,14(s, 2H), 8,28(d, 1H, J=3,7 Hz), 7,79(d, 1H, J=1.8 Hz), EUR 7.57(d, 1H, J=8.5 Hz), of 7.48(DD, 1H, J=2.3 and 8.5 Hz), 7,31-7,26(m, 1H), 7,17(DD, 1H, J=8,8 and 11.4 Hz), 7,10(DD, 1H, J=1.8 and 8,8 Hz), 3,66(s, 3H), 3, 60 (c, 3H), 2,41 (c, 3H), LC/MS: retention time: 11,36 min; purity: 99%; MS (mass/charge): 397 (MH+).++
756N4-(3-Chloro-4-methoxyphenyl)-N2-(1,6-dimethylimidazole-5-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,44(s, 1H), of 9.89(s, 1H), 8,21(d, 1H, J=5.6 Hz), of 7.97(s, 1H), of 7.70(s, 1H), 7.62mm(s, 1H), 7,58(s, 1H), 7,46(d, 1H, J=8,5Hz), 6,91(d, 1H, J=8.5 Hz), 4.00 points(s, 3H), of 3.75(s, 3H), 2,32(s, 3H). LC/MS: retention time: 9,25 min; purity: 93%; MS (mass/charge): 413 (MH+).+
757N4-(3,4-Dichlorophenyl)-N2-(1,6-dimethylimidazole-5-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,34(s, 1H), to 9.70(s, 1H), 8,24(d, 1H, J=4,7 Hz), of 7.97(s, 1H), 7,87(s, 1H), 7,68(s, 1H), 7,58(s, 1H), 7,55(d, 1H, J=8.5 Hz), 7,37(d, 1H, J=8.5 Hz), to 4.01(s, 3H), 2,32(s, 3H). LC/MS: retention time: 11,58 min; purity: 91%; MS (mass/charge): 417 (MH+).+
758N2-(1,6-Dimethylimidazole-5-yl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,70(s, 1H), 10,51(s, 1H), 8,16(d, 1H, J=4.9 Hz), 7,95(s, 1H), 7,74(s, 1H), 7,55(s, 1H), 7,17(d, 1H, J=8.5 Hz), 6,69(d, 1H, J=8.5 Hz), 4.00 points(s, 3H), of 2.34(s, 3H), of 1.31(s, 6H). LC/MS: retention time: 8,24 min; purity: 96%; MS (mass/charge): 448 (MH+).++
759N2-(1,6-Dimethylimidazole-5-yl)-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 10,42(s, 1H), 9,84(s, 1H), 8,18(d, 1H, J=3,9 Hz), of 7.96(s, 1H), 7,74(s, 1H), EUR 7.57(s, 1H), 7,45(d, 1H, J=8.5 Hz), 7,20(m, 1H), 6,97(m, 1H), was 4.02(s, 3H), 3,55(s, 3H), of 2.33(s, 3H). LC/MS: retention time: was 9.33 min; purity: 96%; MS (mass/charge): 397 (MH+).+
760N4-(3,4-Dichlorophenyl)-N2-(2-ethylindole-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.25(s, 1H), 10,06(s, 1H), at 8.36(d, 1H, J=1.8 Hz), 8,30(d, 1H, J=4.4 Hz), 8,03(d, 1H, J=2.3 Hz), 7,86(s, 1H), 7,82(DD, 1H, J=2,6 and 8.8 Hz), 7,66(d, 1H, J=8,8 Hz), 7,53(d, 1H, J=8,8 Hz), 7,14(DD, 1H, J=a 1.8 and 8.8 Hz), 4,42 (Qut, 2H, J=7,3 Hz)of 1.50 (t, 3H, J=7,3 Hz), LC/MS: retention time: 12,85 min; purity: 94%; MS (mass/charge): 418 (MH+).++
761N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-N2-(2-ethylindole-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,57(s, 1H), 9,51(s, 1H), of 9.30(s, 1H), 8,21(s, 1H), 8,12(d, 1H, J=4,1 Hz), 8,07(s, 1H), 7,51(d, 1H, J=9.1 Hz), 7,40(d, 1H, J=2.3 Hz), 7,27(DD, 1H, J=2,3 and 8.8 Hz), 7,11(DD, 1H, J=1.8 and 9.1 Hz), 6.89 in(d, 1H, J =8,8 Hz), 4,39 (Qut, 2H, J=7,3 Hz)of 1.45 (t, 3H, J=7,3 Hz), 1,40 (c, 6H), LC/MS: retention time: 9,58 min; purity: 93%; MS (mass/charge): 448 (MH+).+ +-
762N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-n-propionate-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,14(s, 1H), 9,82(s, 1H), of 8.25(d, 1H, J=4.4 Hz), by 8.22(s, 1H), of 8.06(d, 1H, J=2.3 Hz), 7,83(s, 1H), 7,74(DD, 1H, J=2.3 and 9.1 Hz), EUR 7.57(d, 1H, J=9.1 Hz), 7,50(d, 1H, J=9.1 Hz), 7,27(DD, 1H, J=2.3 and 9.1 Hz), 4,34(t, 2H, J=7,33 Hz), 1.91 a (sextet, 2H, J=7,3 Hz), or 0.83 (t, 3H, J=7,3 Hz), LC/MS: retention time: 12,80 min; purity: 92%; MS (mass/charge): 432 (MH+).++
763N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(2-n-propionate-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,77(s, 1H), 10,33(s, 1H), 10,07(s, 1H), to 8.20(d, 1H, J=5.3 Hz), 8,15(s, 1H), 7,81(s, 1H), 7,54(d, 1H, J=9.1 Hz), 7.23 percent-to 7.18(m, 3H), 6,86(d, 1H, J=9.1 Hz), 4,32(t, 2H, J=7,3 Hz), 1,90(sextet, 2H, J=7,3 Hz)of 1.36(s, 6H), of 0.82 (t, 3H, J=7,3 Hz), LC/MS: retention time: the remaining 9.08 min; purity: 98%; MS (mass/charge): 462 (MH+).++
764N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(2-n-propionate-6-yl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 10,56(s, 1H), 9,29(s, 1H), which is 9.09(s, 1H), 8,17(d, 1H, J=0.8 Hz), 8,13(d, 1H, J=0.8 Hz), of 8.09(d, 1H, J=3.8 Hz), of 7.48(d, 1H, J=9.1 Hz), 7,41(d, 1H, J=2.3 Hz), 7,29(DD, 1H, J=2.3 and 9.1 Hz), 7,12(DD, 1H, J=2,3 and 8.8 Hz), to 6.88 (d, 1H, J=8,8 Hz), 4,30 (t, 2H, J=7,33 Hz), 1,87 (sextet, 2H, J=7,3 Hz), 1,40 (c, 6H), of 0.82 (t, 3H, J=7,3 Hz), LC/MS: retention time: 10,48 min; purity: 97%; MS (mass/charge): 462 (MH+).++
765N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-n-propionate-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.93(s, 1H), 9,67(s, 1H), 8,28(s, 1H), 8,24(d, 1H, J=4,1 Hz), with 8.05(d, 1H, J=2.3 Hz), to $ 7.91(s, 1H), 7,88(DD, 1H, J=2,6 and 8.8 Hz), to 7.61(d, 1H, J=8,8 Hz), 7,51(d, 1H, J=8,8 Hz), 7,15(d, 1H, J=8,8 Hz), 4,28(t, 2H, J=7,3 Hz), 1,90 (sextet, 2H, J=7,3 Hz)0,86 (t, 3H, J=7,3 Hz), LC/MS: retention time: 13,66 min; purity: 91%; MS (mass/charge): 432 (MH+).++
766N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(1-methylindol-6-yl)-2,4-pyrimidinediamine salt DL-camphor-1-sulfonic acid1H NMR(DMSO-d6): d 10,69(s, 1H), to 10.09(s, 1H), 9,88(s, 1H), 8,21(d, 1H, J=4,7 Hz), to $ 7.91(d, 1H, J=0.8 Hz), 7,83(s, 1H), to 7.61(d, 1H, J=8.5 Hz), 7,29(DD, 1H, J=2.3 and 8.5 Hz), 7,17(DD, 1H, J=2.3 and 8.5 Hz), 7,13(d, 1H, J=2.3 Hz), 6,85(d, 1H, J=8.5 Hz),3,80(s, 3H), 2,87(d, 1H, AB cut, J=14.6 Hz), and 2.26-to 2.18(m, 1H), 1,92(ushort, 1H, J=4,7 Hz), 1,88 of-1.83(m, 2H), 1,38(s, 6H), 1.32 to-1,21(, 2H), of 1.03(s, 3H), 0,73(s, 3H). LC/MS: retention time: at 9.53 min; purity: 94%; MS(mass/charge): 434(MH+).++-
767N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(1-methylindol-6-yl)-2,4-pyrimidinediamine salt econsultancy acid1H NMR(DMSO-d6): d 10,70(s, 1H), 10,22(s, 1H), 10,00(s, 1H), 8,24(d, 1H, J=4.9 Hz), 7,92(d, 1H, J=0.8 Hz), 7,80(s, 1H), 7,63(d, 1H, J=8,8 Hz), 7,28(DD, 1H, J=2,3 and 8.8 Hz), 7,16(d, 1H, J=1.8 and 8.5 Hz), 7,11(d, 1H, J=2.3 Hz), 6, 84 (d, 1H, J=8.5 Hz), 3,80 (c, 3H), 2,46 (Qut, 1H, J=7,3 Hz), 1,38 (c, 6H), of 1.06 (t, 3H, J=7,3 Hz), LC/MS: retention time: 9,52 min; purity: 97%; MS (mass/charge): 434 (MH+).++-
768N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(1-methylindol-6-yl)-2,4-pyrimidinediamine salt p-hydroxybenzenesulfonic acid1H NMR(DMSO-d6): d 10,69(s, 1H), 10,17(s, 1H), 9,92(s, 1H), 8,21(d, 1H, J=4,7 Hz), 7,92(d, 1H, J=0.8 Hz), 7,81(s, 1H), 7.62mm(d, 1H, J=8.5 Hz), 7,38(TD, 2H, J=2,6 and 8.8 Hz), J =7,28(DD, 1H, J=2.3 and 8.5 a Hz), 7,16(d, 1H, J=1.8 and 8.5 Hz), 7,11 (d, 1H, J=2.3 Hz), at 6.84 (d, 1H, J=8.5 Hz), only 6.64 (dt, 2H, J=2,6 and 8.8 Hz), 3,81 (c, 3H), 1,37 c, 6H), LC/MS: retention time: 9,51 min; purity: 97%; MS (mass/charge): 434 (MH+).++-
769N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(1-methylindol-6-yl)-2,4-pyrimidinediamine salt benzosulfimide acid1H NMR(DMSO-d6): d 10,70(s, 1H), 10,28(s, 1H), 10,00(s, 1H), they were 8.22(d, 1H, J=4.9 Hz), 7,94(d, 1H, J=0.8 Hz), 7,78(s, 1H), to 7.64(d, 1H, J=8,8 Hz), 7,60-7,56(m, 2H), 7,33-7,26(m, 4H), to 7.15(d, 1H, J=1,8 and 8.5 Hz), 7,10(d, 1H, J=2.3 Hz), at 6.84 (d, 1H, J=8.5 Hz), 3,82 (c, 3H), 1,37 (c, 6H), LC/MS: retention time: 9,51 min; purity: 97%; MS (mass/charge): 434 (MH+).++-
770N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(1-methylindol-6-yl)-2,4-pyrimidinediamine salt of hydrochloric acid1H NMR(DMSO-d6): d a 10.74(s, 1H), of 10.21(s, 2H), compared to 8.26(d, 1H, J=4.9 Hz), 7,92(d, 1H, J=0.8 Hz), 7,82(s, 1H), 7.62mm(d, 1H, J=8,8 Hz), 7,27(DD, 1H, J=2.3 and 8.5 Hz), 7,21(d, 1H, J=2.3 Hz), 7,18(DD, 1H, J=the 1.8 and 8.5 Hz), 6,86(d, 1H, J=8,8 Hz), 3,79 (c, 3H), 1,38 (c, 6H), LC/MS: retention time: 9,52 min; purity: 98%; MS (mass/charge): 434 (MH+).++-
771N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(2-methoxyethyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,18(s, 1H), to 9.91(s, 1H), 8,21(d, 1H, J=4,7 Hz), 7,98(d, 1H, J=2.3 Hz), of 7.90(s, 1H), 7,81(s, 1H), 7,66(iscd, 1H, J=8,8 Hz), 7,60(d, 1H, J=9.1 Hz), 7,46(d, 1H, J=9.1 Hz), 7,37(DD, 1H, J=2,3 and 8.8 Hz), 4,48(t, 2H, J=5,2 Hz), of 3.69 (t, 2H, J=5,2 Hz), 3,12 (c, 3H, LC/MS: retention time: 12,23 min; purity: 91%; MS (mass/charge): 448 (MH+).++-
772N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(2-methoxyethyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,45(s, 1H), 10,33(s, 1H), 8,27(d, 1H, J=4.9 Hz), to 7.93(s, 1H), 7,81(d, 1H, J=1.5 Hz), 7,74(d, 1H, J=2.3 Hz), the 7.65(d, 1H, J=8,8 Hz), 7,54(DD, 1H, J=2.3 and 9.1 Hz), 7,37(DD, 1H, J=of 2.6 and 9.1 Hz), 7,10(d, 1H, J==8,8 Hz)to 4.52 (t, 2H, J=5,2 Hz), 3,83 (c, 3H), of 3.73 (t, 2H, J=5,2 Hz), and 3.16 (c, 3H), LC/MS: retention time: 12,23 min; purity: 91%; MS (mass/charge): 448 (MH+).++-
773N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(2-methoxyethyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,78(s, 1H), 10,35(s, 1H), 10,19(s, 1H), 8,21(d, 1H, J=4.9 Hz), 7,0 (, 1H), 7,87(s, 1H), 7,60(d, 1H, J=8,8 Hz), was 7.36(DD, 1H, J=a 1.8 and 8.8 Hz), 7,21(DD, 1H, J=1.8 and 8.5 Hz), 7,17(s, 1H), 6.87 in(d, 1H, J=8.5 Hz), 4,51 (t, 2H, J=5.3 Hz), 3,71 (t, 3H, J=5.3 Hz), and 3.16 (c, 3H), 1,36 (c, 6H), LC/MS: retention time: 8,53 min; purity: 91%; MS (mass/charge): 478 (MH+).++-
7745-fluoro-N4-(4-fluoro-3-methoxyphenyl)-N2-[1-(2-methoxyethyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,19(s, 1H), to 9.93(s, 1H), to 8.20(d, 1H, J=4,7 Hz), of 7.90(s, 2H), to 7.61(d, 1H, J=8,8 Hz), 7,44(DD, 1H, J=2,6 and 8.8 Hz), 7,37(DD, 1H, J=a 2.0 and 8.8 Hz), 7,29-7,26(m, 1H), 7,13(DD, 1H, J=8,8 and 11.1 Hz), a 4.53(t, 2H, J=5.3 Hz), to 3.73 (t, 3H, J=5.3 Hz), 3,62 (c, 3H), 3,17 (c, 3H), LC/MS: retention time: 9,60 min; purity: 95%; MS (mass/charge): 427 (MH+).++-
775N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(2-methoxyethyl)indazol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,08(s, 1H), 9,96(s, 1H), compared to 8.26(d, 1H, J=4.4 Hz), 8,03(d, 1H, J=2.3 Hz), to $ 7.91(d, 1H, J=0.8 Hz), 7,82(s, 1H), of 7.70(DD, 1H, J=2,3 and 8.8 Hz), 7,60(d, 1H, J=8,8 Hz), 7,49(d, 1H, J=8,8 Hz), 7,19(DD, 1H, J=a 1.8 and 8.8 Hz), 4,24 (t, 2H, J=5.3 Hz), 3,61 (t, 3H, J=5.3 Hz), 3,06 (c, 3H), LC/MS: retention time: 13,66 min; purity: 93%; MS (mass/charge): 448 (MH+).+ +-
776N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(2-methoxyethyl)indazol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,02(users, 2H), 8,24(d, 1H, J=4,7 Hz), 7,95(d, 1H, J=0.8 Hz), 7,83(s, 1H), 7,79(d, 1H, J=2.6 Hz), 7,63(d, 1H, J=8,8 Hz), 6,59(DD, 1H, J=2.6 and 9.1 Hz), 7,21(DD, 1H, J=a 1.8 and 8.8 Hz), 7,09(d, 1H, J=9.1 Hz), 4,25 (t, 2H, J=5.3 Hz), 3,82 (c, 3H), 3,63 (t, 3H, J=5.3 Hz), 3,09 (c, 3H), LC/MS: retention time: of 10.93 min; purity: 96%; MS (mass/charge): 443 (MH+).++-
777N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(2-methoxyethyl)indazol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,71(s, 1H), 10,18(users, 2H), to 8.20(d, 1H, J=4.9 Hz), to $ 7.91(d, 1H, J=0.8 Hz), of 7.75(s, 1H), EUR 7.57(d, 1H, J=8.5 Hz), 7.23 percent-to 7.15(m, 3H), for 6.81(d, 1H, J=8,8 Hz), 4,24(t, 2H, J=5.3 Hz), 3,61(t, 3H, J=5.3 Hz), 3,06(s, 3H), 1,33 (c, 6H), LC/MS: retention time: 9,59 min; purity: 96%; MS (mass/charge): 479 (MH+).++-
7785-fluoro-N4-(4-fluoro-3-methoxyphenyl)-N2-[1-(2-methoxyethyl)indazol-6-yl]-2,4-pyrimidinediamine1H NMR(DM what About-d6): d 9,92(users, 2H), 8,23(d, 1H, J=4.4 Hz), 7,94(d, 1H, J=0.8 Hz), to $ 7.91(s, 1H), to 7.59(d, 1H, J=8.5 Hz), of 7.48(DD, 1H, J=2,6 and 8.8 Hz), 7,34-7,30(m, 1H), 7,21(DD, 1H, J=a 1.8 and 8.8 Hz), to 7.15(DD, 1H, J=8,8 and 11.1 Hz), 4,24 (t, 2H, J=5.3 Hz), to 3.64 (t, 3H, J=5.3 Hz), 3,61 (c, 3H), 3,06 (c, 3H), LC/MS: retention time: of 10.93 min; purity: 96%; MS (mass/charge): 427 (MH+).+-
779N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(1-methylethyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d accounted for 10.39(s, 1H), 10,27(s, 1H), compared to 8.26(d, 1H, J=4.9 Hz), to 7.93(s, 1H), 7,81(d, 1H, J=1.4 Hz), 7,74(d, 1H, J=2.3 Hz), to 6.67(d, H, J=9.1 Hz), 7,54(DD, 1H, J=2.3 and 9.1 Hz), 7,37(DD, 1H, J=the 1.8 and 8.8 Hz), to 7.09(d, 1H, J=9.1 Hz), 4,94 (kV, 1H, J=6,7 Hz), 3,83 (c, 3H), 1,476 (d, 6H, J=6,7 Hz), LC/MS: retention time: 10,94 min; purity: 97%; MS (mass/charge): 427 (MH+).+
780N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(1-methylethyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d and 10.20(s, 1H), to 9.91(s, 1H), compared to 8.26(d, 1H, J=4,7 Hz), 8,02(d, 1H, J=2.3 Hz), 7,94(s, 1H), 7,86(s, 1H), 7,68(d, 1H, J=8,8 Hz), 7,66(d, 1H, J=9.1 Hz), 7,50(d, 1H, J=8,8 Hz), 7,41(DD, 1H, J=1.8 and 9.1 Hz), 4.95 points(square, 1H, J=6,7 Hz)of 1.47 (d, 6H, J=6,7 Hz), LC/MS: retention time: 13,92 min; purity: 97%; MS (mass/charge): 432 (MH+)./td> +
781N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(1-methylethyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.76(s, 1H), 10,32(s, 1H), 10,11(s, 1H), 8,19(d, 1H, J=5.3 Hz), of 7.90(s, 1H), 7,89(s, 1H), 7.62mm(d, 1H, J=8,8 Hz), was 7.36(DD, 1H, J=a 1.8 and 8.8 Hz), 7,19(d, 2H, J=8,9 Hz), 6.87 in(d, 1H, J=8,8 Hz), 4,91 (kV, 1H, J=6.4 Hz), the 1.44 (d, 6H, J=6.4 Hz), 1,36 (c, 6H), LC/MS: retention time: 9,60 min; purity: 96%; MS (mass/charge): 462 (MH+).+
7825-fluoro-N4-(4-fluoro-3-methoxyphenyl)-N2-[1-(1-methylethyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,35(s, 1H), of 10.21(s, 1H), of 8.25(d, 1H, J=4.9 Hz), of 7.90(s, 1H), 7,88(s, 1H), 7,65(d, 1H, J=8.1 Hz), the 7.43(DD, 1H, J=2,3 and 8.8 Hz), 7,35(DD, 1H, J=a 1.8 and 8.8 Hz), 7,26-7,22(m, 1H), 7,14(DD, 1H, J=8,8 and 11.1 Hz), of 4.95 (q, 1H, J=6,4 Hz)and 3.59 (c, 3H), of 1.46 (d, 6H, J=6.4 Hz), LC/MS: retention time: 10,96 min; purity: 96%; MS (mass/charge): 411 (MH+).+
783N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(1-methylethyl)indazol-6-yl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 10,10(s, 2H), of 8.25(d, 1H, J=4,7 Hz), to 7.93(s, 1H), 7,86(s, 1H), 7,78(d, 1H, J=2.3 Hz), to 7.64(d, 1H, J=8,8 Hz), 7,56(DD, 1H, J=2,3 and 8.8 Hz), 7,18(d, 1H, J=8,8 Hz), 7,10(d, 1H, J=the 8.9 Hz), 4,45(square, 1H, J=6.4 Hz), 3,82 (c, 3H), of 1.35 (d, 6H, J=6.4 Hz), LC/MS: retention time: of 12.26 min; purity: 97%; MS (mass/charge): 427 (MH+).+
784N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(1-methylethyl)indazol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,06(s, 1H), to 9.93(s, 1H), 8.30 to(d, 1H, J=4.3 Hz), of 8.06(d, 1H, J=2.3 Hz), to 7.93(s, 2H), 7,76(DD, 1H, J=2,3 and 8.8 Hz), to 7.64(d, 1H, J=8,8 Hz), 7,54(d, 1H, J=8,8 Hz), 7,21(DD, 1H, J=the 1.8 and 8.8 Hz), 4,55(square, 1H, J=6,4 Hz)to 1.38 (d, 6H, J=6.4 Hz), LC/MS: retention time: 15,20 min; purity: 97%; MS (mass/charge): 432 (MH+).+
785N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(1-methylethyl)indazol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.76(s, 1H), 10,14(s, 2H), 8,24(d, 1H, J=4.9 Hz), to 7.93(s, 1H), 7,88(s, 1H), to 7.61(d, 1H, J=8,8 Hz), 7,27-7,16(m, 3H), to 6.88(d, 1H, J=8,8 Hz), 4,50(square, 1H, J=6,4 Hz)to 1.37(d, 6H, J=6.4 Hz), of 1.35(s, 6H). LC/MS: retention time: 10,91 min; purity: 97%; MS (mass/charge): 462 (MH+).+
786(S)-N4-[2-Methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl]-5-fluoro-N2-[1-(1-methylethyl)indazol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,77(s, 1H), 10,14(s, 1H), to 9.93(s, 1H0, by 8.22(d, 1H, J=4,7 Hz), to 7.93(s, 1H), 7,92(s, 1H), 7,60(d, 1H, J=8.5 Hz), 7,27(DD, 1H, J=2.3 and 8.5 Hz), 7,21-7,16(m, 2H), 6.90 to(d, 1H, J=8,5 Hz)and 4.65(Qut, 1H, J=6,7 Hz), 4,49 (kV, 1H, J=6,4 Hz)of 1.41 (d, 3H, J=6,7 Hz)of 1.36 (d, 6H, J=6.4 Hz), LC/MS: retention time: 10,30 min; purity: 95%; MS (mass/charge): 448 (MH+).+
787N2-[1-(3-Acetyloxybenzoic)indazol-5-yl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,17(s, 1H), 9,90(s, 1H), 8,21(d, 1H, J=4,7 Hz), of 7.97(d, 1H, J=2.3 Hz), of 7.90(DD, 1H, J=2,3 and 8.8 Hz), to 7.59(d, 1H, J=8,8 Hz), 7,47(d, 1H, J=8,8 Hz), 7,38(DD, 1H, J=a 2.0 and 8.8 Hz), to 4.41(d, 2H, J=6,7 Hz), 3,88 (t, 2H, J=6.4 Hz), 2,07 (q, 2H, J=6,7 Hz), 1,89 (c, 3H).++-
788N2-[1-(3-Acetyloxybenzoic)indazol-5-yl]-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,32(s, 1H), 10,19(s, 1H), 8,24(d, 1H, J=5.3 Hz), to 7.93(s, 1H), a 7.85(s, 1H), 7,74(d, 1H, J2,3 Hz), 7,63(d, 1H, J=8,8 Hz), 7,54(DD, 1H, J=2.3 and 9.1 Hz), 7,40(DD, 1H, J=2,3 and 8.8 Hz), to 7.09(d, 1H, J=9.1 Hz), 4, 45 (t, 2H, J 6,7 Hz), 3,93 (t, 2H, J=6.4 Hz), 3,83 (c, 3H), 2,11 (q, 2H, J=6,7 Hz), 1.93 and (c, 3H).++-
789N2-[1-(3-Acetyloxybenzoic)indazol-5-yl]-5-fluoro-N4-(4-fluoro-3-methoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,31(s, 1H), 10,15(s, 1H), 8,24(d, 1H, J=4,7 Hz), to $ 7.91(s, 2H), to 7.61(d, 1H, J=8,8 Hz), 7,44(DD, 1H, J=2,3 and 8.8 Hz), 7,38(DD, 1H, J=1.8 and 9.1 Hz), 7,27-7,25(m, 1H), 7,15(DD, 1H, J=8,8 and 11.1 Hz), of 4.45(t, 2H, J=6,7 Hz)to 3.92 (t, 2H, J=6.4 Hz), 3,62 (c, 3H), 2,11 (INM. kV, 2H, J=6.4 Hz), 1.93 and (c, 3H).++-
790N2-[1-(3-Acetyloxybenzoic)indazol-6-yl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,96(s, 1H), 9,83(s, 1H), 8,27(d, 1H, J=4,1 Hz), of 8.09(d, 1H, J=2.3 Hz), 7,94(s, 1H), 7,92(s, 1H), of 7.75(DD, 1H, J=2,3 and 8.8 Hz), 7,63(d, 1H, J=8,8 Hz), 7,53(d, 1H, J=8,8 Hz), 7.23 percent(DD, 1H, J=a 1.8 and 8.8 Hz), 4,20 (t, 2H, J=6,7 Hz), 3,83 (t, 2H, J=6.4 Hz), 2,02 (INM. kV, 2H, J=6.4 Hz), 1,89 (c, 3H).++-
791N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-f the PR-N2-[1-(3-hydroxypropyl)indazol-6-yl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d is 10.68(s, 1H), 9,84(s, 1H), 9,74(s, 1H), 8,18(d, 1H, J=4.4 Hz), of 7.90(s, 1H), 7,56(s, 1H), 7,58(d, 1H, J=8,8 Hz), 7,32-7,24(m, 3H), 6,85(d, 1H, J=8,8 Hz), 4,20(t, 2H, J=6,7 Hz), 3,29(t, 2H, J=6.4 Hz), 1,87(ISCCP, 2H, J=6,7 Hz), 1,38 (c, 6H).++-
792N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-methoxypropyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,42(s, 1H), 10.30 a.m. (s, 1H), compared to 8.26(d, 1H, J=5,2 Hz), to 7.93(s, 1H), 7,82(d, 1H, J=1.8 Hz), 7,74(d, 1H, J=2.3 Hz), 7,60(d, 1H, J=9.1 Hz), 7,53(DD, 1H, J=2.3 and 9.1 Hz), 7,38(DD, 1H, J=the 1.8 and 9.1 Hz), to 7.09(d, 1H, J=9.1 Hz), and 4.40 (t, 2H, J=6,7 Hz), 3,83 (c, 3H), 3,23 (t, 2H, J=6.4 Hz), 3,17 (c, 3H), 2,02 (INM. kV, 2H, J=6,7 Hz).++-+
793N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(3-methoxypropyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,36(s, 1H), 10,13(s, 1H), 8.30 to(d, 1H, J=5.0 Hz), 8,01(d, 1H, J=2.3 Hz), 7,95(s, 1H), 7,86(s, 1H), 7,68(DD, 1H, J=2,3 and 8.8 Hz), to 7.61(d, 1H, J=9.1 Hz), 7,51(d, 1H, J=8,8 Hz), 7,41(DD, 1H, J=1.8 and 9.1 Hz), 4, 41 (t, 2H, J=6,7 Hz), 3,19 (c, 3H), 3,24 (t, 2H, J=6.4 Hz), 2,03 (q, 2H, J=6,7 Hz).++-
794 N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(3-methoxypropyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,77(s, 1H), 10,42(s, 1H), 10,27(s, 1H), 8,23(d, 1H, J=4.3 Hz), of 7.90(s, 1H), 7,88(s, 1H), 7,56(d, 1H, J=8,8 Hz), 7,37(DD, 1H, J=a 1.8 and 8.8 Hz), 7,21(iscd, 2H, J=9.1 Hz), 6.87 in(d, 1H, J=9.1 Hz), 4,39(t, 2H, J=6,7 Hz), 3,21 (t, 2H, J=6.4 Hz), 3,17 (c, 3H), 2.00 (evens INM. kV, 2H, J=6,7 Hz), 1,36 (c, 6H).++-
795(S)-5-fluoro-N2-[1-(3-methoxypropyl)indazol-5-yl]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.73(s, 1H), 10,32(s, 1H), 10,15(s, 1H), 8,17(d, 1H, J=4.9 Hz), the 7.85(s, 1H), 7,83(s, 1H), 7,51(d, 1H, J=8,8 Hz), 7,33(DD, 1H, J=2.1 and 9.1 Hz), 7,16(DD, 2H, J=2.3 and 9.1 Hz), at 6.84(d, 1H, J=8,8 Hz), 4,60(Qut, 1H, J=6,7 Hz), 4,34 (t, 2H, J=6,7 Hz), 3,17 (t, 2H, J=6.4 Hz), 3,12 (c, 3H), 1,95 (q, 2H, J=6,7 Hz)of 1.36 (d, 3H, J=6,7 Hz).++-
796N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-methoxypropyl)indazol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,16(s, 2H), of 8.27(d, 1H, J=4,7 Hz), 7,95(d, 1H, J=0.8 Hz), 7,80(s, 1H), 7,78(d, 1H, J=8,8 Hz), the 7.65(d, 1H, J=2.3 and 9.1 Hz), 7,58(DD, 1H, J=2.3 and 9.1 Hz), 7,20(DD, 1H, J=a 1.8 and 8.8 Hz), to 7.09(d, 1H, J=9.1 Hz), is 4.15 (t, 2H, J=6,7 Hz), 3,82 (c, 3H), of 3.13 (t, 2H, J=6,7 Hz), 3,12 (, 3H), 1,89 (ICCT, 2H, J=6,7 Hz).++-
797N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(3-methoxypropyl)indazol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,13(s, 1H), 10,02(s, 1H), 8,31(d, 1H, J=4,1 Hz), of 8.06(d, 1H, J=2.3 Hz), 7,95(s, 1H), 7,87(s, 1H), 7,74(DD, 1H, J=2,3 and 8.8 Hz), the 7.65(d, 1H, J=8.5 Hz), 7,54(d, 1H, J=8,8 Hz), 7,22(d, 1H, J=8.5 Hz), 4,17(t, 2H, J=6,7 Hz), 3,17 (t, 2H, J=6,7 Hz), 3,12 (c, 3H), 1.91 a (INM. kV, 2H, J=6,7 Hz).++-
798N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(3-methoxypropyl)indazol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.73(s, 1H), 9,92(s, 2H), 8,21(d, 1H, J=4,7 Hz), 7,92(s, 1H), 7,89(s, 1H), 7,58(d, 1H, J=8,8 Hz), 7,29-7,24(m, 3H), 6,85(d, 1H, J=8.5 Hz), 4,17(t, 2H, J=6,7 Hz), 3,14(ICCT, 2H, J=6.4 Hz), of 3.13(s, 3H), 1,92(INM. kV, 2H, J=6.4 Hz), 1,38 (c, 6H).+++
799(S)-5-fluoro-N2-[1-(3-methoxypropyl)indazol-6-yl]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.76(s, 1H), 10,11(s, 2H), 8,23(d, 1H, J=4,7 Hz), 7,9 (, 1H), 7,86(s, 1H), 7.62mm(d, 1H, J=8.5 Hz), 7,28-7,19(m, 3H), to 6.88(d, 1H, J=8.5 Hz), with 4.64(Qut, 1H, J=6,7 Hz), 4,17(t, 2H, J=6,7 Hz), and 3.16(ICCT, 2H, J=6,7 Hz), 3,13 (c, 3H), 1.91 a (INM. kV, 2H, J=6,7 Hz)of 1.41 (d, 3H, J=6,7 Hz).++-
800N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(2-trifluoromethyl-1H-benzimidazole-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,17(s, 1H), to 8.20(d, 1H, J=4.9 Hz), the 7.85(s, 1H), 7,69(d, 1H, J=2.3 Hz), to 7.61(d, 1H, J=8,8 Hz), to 7.59(DD, 1H, J=2,3 and 8.8 Hz), 7,39(DD, 1H, J=a 2.0 and 8.8 Hz),? 7.04 baby mortality(d, 1H, J=9.1 Hz), 3,76(s, 3H).++++
801N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-trifluoromethyl-1H-benzimidazole-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,84(s, 1H), to 9.70(s, 1H), 8,19(d, 1H, J=4,1 Hz), with 8.05(d, 1H, J=2.3 Hz), of 7.96(s, 1H), of 7.75(DD, 1H, J=2,3 and 8.8 Hz), 7,60(d, 1H, J=9.1 Hz), 7,47-the 7.43(m, 2H).++++
802N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(2-trifluoromethyl-1H-benzimidazole-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,71(s, 1H), 10,26(s, 1H), of 10.21(s, 1H), they were 8.22(d, 1H, J=4,Hz), 7,88(s, 1H), to 7.61(d, 1H, J=8,8 Hz), 7,49(DD, 1H, J=2,3 and 8.8 Hz), 7,24(s, 1H), 7,22(s, 1H), 6,86(d, 1H, J=8,8 Hz)of 1.36(s, 6H).++-+
803(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-(2-trifluoromethyl-1H-benzimidazole-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,71(s, 1H), 10,27(s, 1H), 10,22(s, 1H), they were 8.22(d, 1H, J=4.9 Hz), to 7.93(s, 1H), 7.62mm(d, 1H, J=8,8 Hz), 7,46(DD, 1H, J=2,3 and 8.8 Hz), 7,24(s, 1H), 7,21(s, 1H), 6.89 in(d, 1H, J=8,8 Hz), 4,66(Qut, 1H, J=6,7 Hz)of 1.40(d, 3H, J=6,7 Hz).++-
804N2-(3-Amino-1-methylindol-5-yl)-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,13(s, 1H), 9,94(s, 1H), 8,17(d, 1H, J=4.9 Hz), 7,76(s, 1H), of 7.75(d, 1H, J=2.3 Hz), to 7.61(DD, 1H, J=2.3 and 9.1 Hz), 7,44(s, 2H), 7,05(d, 1H, J=9.1 Hz), 3,80(s, 3H), 3,79(s, 3H).++
805N2-(3-Amino-1-methylindol-5-yl)-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,17(s, 1H), 9,90(s, 1H), 8,21(d, 1H, J=4,7 Hz), of 7.97(d, 1H, J=2.3 Hz), of 7.90(DD, 1H, J=2,3 and 8.8 Hz), to 7.59(d, 1H, J=8,8 Hz), 7,47(d,1H, J=8,8 Hz), 7,38(DD, 1H, J=a 2.0 and 8.8 Hz), to 4.41(d, 2H, J=6,7 Hz), 3,88 (t, 2H, J=6.4 Hz), 2,07 (q, 2H, J=6,7 Hz), 1,89 (c, 3H).+
806N2-(3-Amino-1-methylindol-5-yl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d is 10.75(s, 1H), 10,46(s, 1H), the 10.40(s, 1H), they were 8.22(d, 1H, J=4.9 Hz), 7,79(s, 1H), 7,54(DD, 1H, J=2,3'an d8,8 Hz), of 7.48(d, 1H, J=9.1 Hz), 7,28(iSCSI, 1H), 7,22(DD, 1H, J=2.3 and 9.1 Hz), 6,54(d, 1H, J=8,8 Hz), of 3.84(s, 3H), 1,34 (c, 6H).++
807(S)-N2-(3-Amino-1-methylindol-5-yl)-5-fluoro-N4-(2-methyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.76(s, 1H), 10,38(s, 1H), 10,28(s, 1H), to 8.20(d, 1H, J=5.3 Hz), 7,80(s, 1H), 7,53(d, 1H, J=9.1 Hz), of 7.48(d, 1H, J=9.1 Hz), 7,27(s, 1H), 7,25(s, 1H), 6.87 in(d, 1H, J=9.1 Hz), 4,63(Qut, 1H, J=6,7 Hz), 3,83(s, 3H), 1, 38 (d, 3H, J=6,7 Hz).++
808N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(2-methyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d at 9.53(s, 1H), 9,40(s, 1H), 8,14(d, 1H, J=3.8 Hz), and 13(C, 1H), 7,86(d, 1H, J=2.6 Hz), 7,72-to 7.67(m, 2H), to 7.59(d, 1H, J=8,8 Hz), 7,11(d, 1H, J=9.1 Hz), 3,83(s, 3H), of 2.72(s, 3H).++-+
809N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-methyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 9.93(s, 2H), 8,28(d, 1H, J=4,8 Hz)to 8.12(d, 1H, J=2.6 Hz), 8,07(s, 1H), 7,81(DD, 1H, J=2.3 and 9.1 Hz), 7,66(s, 2H), 7,56(d, 1H, J=8,8 Hz)of 2.75(s, 3H).++-+
810N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(2-methyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,70(s, 1H), of 9.56(s, 1H), 9,40(s, 1H), 8,21(s, 1H), 8,12(d, 1H, J=3.8 Hz), 7,79(DD, 1H, J=2.3 and 9.1 Hz), 7,55(d, 1H, J=8,8 Hz), 7,52(s, 1H), 7,31(DD, 1H, J=2,3 and 8.8 Hz), to 6.88(d, 1H, J=8,8 Hz), of 2.72(s, 3H), 1.39 in (c, 6H).++-+
811(S)-5-fluoro-N2-(2-methyl-3H-benzimidazole-5-yl)-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,69(s, 1H), 9,58(s, 1H), 9,42(s, 1H), 8,23(s, 1H), 8,12(d, 1H, J=3.5 Hz), 7,74(DD, 1H, J=2,3 and 8.8 Hz), EUR 7.57(d, 1H, J=9.1 Hz), 7,53(d, 1H, J=2.3 Hz), 7,29(DD, H, J=2,3 and 8.8 Hz), 6,91(d, 1H, J=8,8 Hz), with 4.64(Qut, 1H, J=6,7 Hz), 2,71 (c, 3H), of 1.42 (d, 3H, J=6,7 Hz).++-+
812N2-(1,3-Dimethylindole-6-yl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,06(s, 1H), at 9.53(s, 1H), 9,44(s, 1H), 8,16(d, 1H, J=3.5 Hz), 7,83(s, 1H), 7,53(d, 1H, J=8.5 Hz), was 7.45(d, 1H, J=8,8 Hz), 7,30(d, 1H, J=8.5 Hz), to 7.15(DD, 1H, J=2,3 and 8.8 Hz), 3,67(s, 3H), of 2.33(s, 3H), of 1.36(s, 6H).+
813N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3-methyl-1H-indazol-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 12,21(s, 1H), 11,02(s, 1H), of 9.30(s, 1H), 9,12(s, 1H), 8,11(d, 1H, J=3.5 Hz), of 7.90(s, 1H), 7,69(d, 1H, J=8.5 Hz), the 7.43(d, 1H, J=8.5 Hz), 7,33(d, 1H, J=8,8 Hz), 7,19(d, 1H, J=8,8 Hz), was 2.34(s, 3H), of 1.36(s, 6H).+
814N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(3-methoxypropyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,10(s, 1H), which 9.22(s, 1H), 9,19(s, 1H), 8,12(d, 1H, J=3.5 Hz), with 8.05(s, 1H), to 7.84(s, 1H), EUR 7.57(d, 1, J=8.5 Hz), 7,50(d, 1H, J=8,8 Hz), 7,46(d, 1H, J=8,8 Hz), 7,35(d, 1H, J=8,8 Hz), 4,37(t, 2H, J=6.4 Hz), up 3.22(t, 2H, J=6.4 Hz), 3,19 (c, 3H), 2.00 (evens INM. kV, 2H, J=6.4 Hz), 1,42 (c, 6H).+
815N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-[3-(N-phthalimidopropyl)]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,36(s, 1H), of 10.25(s, 1H), 8,21(d, 1H, J=4.9 Hz), the 7.85(s, 1H), 7,79 to 7.75(m, 5H), to 7.67(d, 1H, J=2.3 Hz), 7,63(d, 1H, J=8,8 Hz), 7,49(DD, 1H, J=2,3 and 8.8 Hz), 7,32(DD, 1H, J=1.8 and 9.1 to Hz), 7,03(d, 1H, J=8,8 Hz), 4,39 (t, 2H, J=6,7 Hz), 3,75 (c, 3H), of 3.57 (t, 2H, J=6,7 Hz), 2,12 (INM. kV, 2H, J=6,7 Hz).+
816N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-[3-(N-phthalimidopropyl)]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,24(s,1H), 9,99(s, 1H), 8,23(d, 1H, J=4,7 Hz), 7,95(d, 1H, J=2.0 Hz), 7,87(s, 1H), 7,80(s, 1H), 7,78-7,73(m, 4H), to 7.64(d, 1H, J=9.1 Hz), was 7.45(d, 1H, J=8,8 Hz), was 7.36(DD, 1H, J=1.8 and 9.1 Hz), to 4.41(t, 2H, J=6,7 Hz), of 3.57 (t, 2H, J=6,7 Hz), 2,12 (INM. kV, 2H, J=6,7 Hz).-
817N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-[3-(N-phthalimidopropyl)]in the azole-5-yl]-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 10,78(s, 1H), 10,45(s, 1H), 10,32(s, 1H), 8,24(d, 1H, J=4.9 Hz), 7,88(s, 1H), 7,87(s, 1H), 7,84-to 7.77(m, 4H), of 7.65(d, 1H, J=8,8 Hz), 7,37(DD, 1H, J=1.8 and 9.1 Hz), 7,20(d, 1H, J=8,8 Hz), 6,86(d, 1H, J=9.1 Hz), 4,43 (t, 2H, J=6,7 Hz), of 3.60 (t, 2H, J=6,7 Hz), 2,16 (INM. kV, 2H, J=6,7 Hz), 1,32 (c, 6H).+
818(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[1-[3-(N-phthalimidopropyl)]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,80(s, 1H), 10,44(s, 1H), 10.30 a.m. (s, 1H), 8,24(d, 1H, J=5.3 Hz), 7,89(s, 1H), 7,87(s, 1H), 7,82-to 7.77(m, 4H), to 7.67(d, 1H, J=8,8 Hz), 7,37(DD, 1H, J=1.8 and 9.1 Hz), 7,22(DD, 1H, J=1,8 and 8.8 Hz), 7,18(s, 1H), 6.89 in(d, 1H, J=8,8 Hz), 4,59 (Qut, 1H, J=6,7 Hz), of 4.44 (t, 2H, J=6,7 Hz), of 3.60 (t, 2H, J=6,7 Hz), 2,16 (INM. kV, 2H, J=6,7 Hz)of 1.35 (d, 3H, J=6,7 Hz).+
819N2-[1-[3-(N-Acetylamino)propyl]indazol-5-yl]-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,22(s, 1H), of 10.05(s, 1H), 8,21(d, 1H, J=4.9 Hz), 7,92(s, 1H), of 7.90(m, 1H), 7,86(s, 1H), of 7.75(d, 1H, J=2.3 Hz), to 7.64(d, 1H, J=9.1 Hz), EUR 7.57(DD, 1H, J=2,3 and 8.8 Hz), 7,39(DD, 1H, J=a 1.8 and 8.8 Hz), to 7.09(d, 1H, J=8,8 Hz), 4,37 (t, 2H, J=7.0 Hz), 3,83 (c, 3H), 3,02 (Qut, 2H, J=7.0 Hz), 1,92 (INM. kV, 2H, J=7.0 Hz), 1,78 (c, 3H). ++
820N2-[1-[3-(N-Acetylamino)propyl]indazol-5-yl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.51(s, 1H), 9,23(s, 1), 8,10(d, 1H, J=3.8 Hz), of 8.04(d, 1H, J=2.3 Hz), 7,95(s, 1H), 7,82(m, 2H), 7,74(DD, 1H, J=2.0 and 9.1 Hz), 7,51(d, 1H, J=9.1 Hz), 7,44(d, 1H, J=9.1 Hz), 7,43(DD, 1H, J=1.8 and 9.1 Hz), 4,30(t, 2H, J=6,7 Hz), 2,95 (Qut, 2H, J=6,7 Hz), 1,87 (INM. kV, 2H, J=7.0 Hz), 1,73 (c, 3H).+
821N2-[1-[3-(N-Acetylamino)propyl]indazol-5-yl]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,77(s, 1H), 10,38(s, 1H), 10,18(s, 1H), 8,21(d, 1H, J=4.9 Hz), of 7.90(s, 3H), to 7.61(d, 1H, J=8,8 Hz), was 7.36(DD, 1H, J=2.0 and 9.1 Hz), 7,21(d, 1H, J=8.5 Hz), 7,18(s, 1H), 6.89 in(d, 1H, J=8.5 Hz), 4,36(t, 2H, J=7.0 Hz), 2,99 (INM. Cut, 2H, J=6,7 Hz), 1,92 (INM. kV, 2H, J=6,7 Hz), 1,78 (c, 3H), 1,36 (c, 6H).+
822N2-[1-[3-(N-Acetylamino)propyl]indazol-5-yl]-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,05(s, 1H), 9,18(s, 1H), 9.15, with(s, 1H), 8,07(d, 1H), 3.5 Hz), 8,01(s, 1H), 7,80(d, 1H, J=63 Hz), 7,79(s, 1H), 7,52(d, 1H, J=8.5 Hz), of 7.48-7,40(m, 2H), 7,31(d, 1H, J=8.5 Hz), the 4.29(t, 2H, J=7.0 Hz), 2,94(Qut, 2H, J=6.4 Hz), 1,86 (INM. kV, 2H, J=7.0 Hz), 1,72 (c, 3H), 1,37 (c, 6H).++
823N2-[1-(3-Aminopropyl)indazol-5-yl]-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.25(s, 1H), of 10.21(s, 1H), 8,21(d, 1H, J=4,8 Hz), 7,97(users, 2H), 7,88(s, 1H), 7,84 for 7.78(m, 2H), of 7.70(d, 1H, J=2.6 Hz), the remaining 9.08(d, 1H, J=9.1 Hz), 7,49(DD, 1H, J=2,6 and 8.8 Hz), was 7.36(DD, 1H, J=a 1.8 and 8.8 Hz), 7,06(d, 1H, J=8,8 Hz), 4,43 (t, 2H, J=6,7 Hz), 3,79 (c, 3H), was 2.76-2,70 (m, 2H), 2.05 is (INM. kV, 2H, J=6,7 Hz).+
824N2-[1-(3-Aminopropyl)indazol-5-yl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.01(s, 1H), made up 9.77(s, 1H), 8,24(d, 1H, J=3.1 Hz), of 8.06(d, 1H, J=2.6 Hz), of 7.96(s, 1H), 7,95(s, 1H), of 7.90-a 7.85(m, 2H), of 7.75(d, 1H, J=8.5 Hz), to 7.67(d, 1H, J=8,8 Hz), 7,53(d, 1H, J=8,8 Hz), 7,47(DD, 1H, J=2.0 and 9.1 Hz), 4,43 (t, 2H, J=6,7 Hz), 2,81-2,77 (m, 2H), 2,14-2,04 (INM. kV, 2H, J=6,7 Hz).+
825N2-[1-(3-Aminopropyl)indazol-5-yl]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxa is in-6-yl)-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 10,77(s, 1H), 10,35(s, 2H), to 8.20(d, 1H, J=5.0 Hz), 7,94(users, 2H), 7,94(s, 1H), 7,86(s, 1H), 7,82-7,79(m, 1H), 7.62mm(d, 1H, J=9.1 Hz), 7,34(DD, 1H, J=1.8 and 9.1 Hz), 7,21(users, 1H), 7,15(DD, 1H, J=a 1.8 and 8.8 Hz), 6,86 (d, 1H, J=8,8 Hz), 4,42 (t, 2H, J=6,7 Hz), was 2.76-to 2.67 (m, 2H), 2,03 (INM. kV, 2H, J=6,7 Hz), 1,32 (c, 6H).+
826(S)-N2-[1-(3-Aminopropyl)indazol-5-yl]-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,78(s, 1H), 10.30 a.m. (s, 2H), 8,18(d, 1H, J=4.9 Hz), 7,93(users, 2H), to $ 7.91(s, 1H), 7,87(s, 1H), 7,83-7,80(m, 1H), 7,63(d, 1H, J=8,8 Hz), was 7.36(DD, 1H, J=a 1.8 and 8.8 Hz), 7,21(users, 1H), 7,17(DD, 1H, J=2.3 and 8.5 Hz), to 6.88 (d, 1H, J=8.5 Hz), br4.61 (Qut, 1H, J=6,7 Hz), 4,42 (t, 2H, J=6,7 Hz), was 2.76-to 2.67 (m, 2H), 2,03 (INM. kV, 2H, J=6,7 Hz)of 1.36 (d, 3H, J=6,7 Hz).+
827N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-hydroxypropyl)indazol-5-yl]-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR(DMSO-d6): d accounted for 10.39(s, 1H), there is a 10.03(s, 1H), to 8.20(d, 1H, J=5.3 Hz), 7,95(s, 1H), 7,80(d, 1H, J=1.8 Hz), 7,74(d, 1H, J=2.6 Hz), to 7.64(d, 1H, J=8,8 Hz), 7,54(DD, 1H, J=2.6 and 9.1 Hz), 7,46(d, 2H, J=8.1 Hz), 7,38(DD, 1H, J=2.1 and 9.1 Hz), 7,10 (d, 2H, J=8.1 Hz), 7,07 (d, 1H, J=8,8 Hz), 4,42 (t, 2H, J=6,7 Hz), 3,82 (c, 3H), 3,37 (t, 2H, J=67 Hz), 2,27 (c, 3H), 1,94 (INM. kV, 2H, J=6,7 Hz).+-
828N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-hydroxypropyl)indazol-5-yl]-2,4-pyrimidinediamine salt of bis-p-toluensulfonate acid1H NMR(DMSO-d6): d as 10.63(s, 1H), 10,23(s, 1H), 8,24(d, 1H, J=5.5 Hz), of 7.97(s, 1H), 7,76(d, 1H, J=1.8 Hz), 7,72(d, 1H, J=2.4 Hz), 7,66(d, 1H, J=9.1 Hz), 7,52(DD, 1H, J=2,6 and 8.8 Hz), 7,47(d, 4H, J=8.1 Hz), 7,35(DD, 1H, J=a 1.8 and 8.8 Hz), 7,10 (d, 4H, J=8.1 Hz), 7,07 (d, 1H, J=9.1 Hz), 4,43 (t, 2H, J=6,7 Hz), 3,82 (c, 3H), 3,38 (t, 2H, J=6.4 Hz), and 2.27 (c, 6H), 1,95 (INM. kV, 2H, J=6,7 Hz).++-
829N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-hydroxypropyl)indazol-5-yl]-2,4-pyrimidinediamine salt benzosulfimide acid1H NMR(DMSO-d6): d 10,38(s, 1H), 10,02(s, 1H), 8,19(d, 1H, J=4,7 Hz), 7,95(s, 1H), 7,80(s, 1H), 7,74(s, 1H), 7,65-7,58(m, 4H), 7,38(d, 1H, J=9.1 Hz), 7,29(s, 3H), 7,07(d, 1H, J=8,8 Hz), 4,42(t, 2H, J=6,7 Hz), 3,82(s, 3H), 3,37(t, 2H, J=6.4 Hz),1,95 (INM. kV, 2H, J=6,7 Hz).+++
830N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-hydroxyprop the Il)indazol-5-yl]-2,4-pyrimidinediamine salt of bis-benzosulfimide acid 1H NMR(DMSO-d6): d 10,29(s, 1H), 9,95(s, 1H), 8,19(d, 1H, J=5,1 Hz), 7,94(s, 1H), 7,81(d, 1H, J=1.8 Hz), of 7.75(d, 1H, J=2.6 Hz), 7,65-7,53(m, 7H), 7,39(DD, 1H, J=a 2.0 and 8.8 Hz), 7,31-7,26(m, 5H), 7,07(d, 1H, J=8,8 Hz), 4,42(t, 2H, J=6,7 Hz), 3,82 (c, 3H), 3,37 (t, 2H, J=6.4 Hz),1,95 (INM. kV, 2H, J=6,7 Hz).++-
831N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-hydroxypropyl)indazol-5-yl]-2,4-pyrimidinediamine cleaners containing hydrochloride salt1H NMR(DMSO-d6): d 10,36(s, 1H), of 10.25(s, 1H), 8,21(d, 1H, J=5.3 Hz), 7,87(s, 1H), to 7.77(d, 1H, J=1.5 Hz), 7,69(d, 1H, J=2.1 Hz), EUR 7.57(d, 1H, J=9.1 Hz), 7,49(DD, 1H, J=2,3 and 8.8 Hz), 7,33(DD, 1H, J=of 2.0 and 9.1 Hz), 7,03(d, 1H, J=8,8 Hz), 4,36 (t, 2H, J=6,7 Hz), 3,78 (c, 3H), of 3.32 (t, 2H, J=6,7 Hz), 1,89 (INM. kV, 2H, J=6,7 Hz).++-
832N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-[3-(N-methylsulfonylamino)propyl]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d or 10.60(s, 1H), 10,52(s, 1H), 8.30 to(d, 1H, J=5.6 Hz), 7,95(s, 1H), 7,81(d, 1H, J=1.8 Hz), 7,73(d, 1H, J=2.3 Hz), 7,69(d, 1H, J=9.1 Hz), 7,52(DD, 1H, J=2,3 and 8.8 Hz), 7,37(DD, 1H, J=of 2.0 and 8.8 Hz), 7,10(users, 1H), to 7.09 (d, 1H, J=9.1 Hz), 4,42 (t, 2H, J=6,7 Hz), 3,83 (c, 3H), 2.95 and (INM. m, 2H), 2,86 (c, 3H), 2.00 (evens INM. kV, 2H, J=6,7 Hz).++ -
833N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-[3-(N-methylsulfonylamino)propyl]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d at 9.53(s, 1H), 9,25(s, 1H), 8,11(d, 1H, J=3.8 Hz), of 8.04(d, 1H, J=2.3 Hz), 7,97(users, 1H), 7,83(s, 1H), 7,73(d, 1H, J=2,3 and 8.8 Hz), 7,53(d, 1H, J=8,8 Hz), 7,44(d, 1H, J=8,8 Hz), 7,43(DD, 1H, J=2,3 and 8.8 Hz), 7, 02 (t, 1H, J=5.3 Hz), 4,34 (t, 2H, J=7.0 Hz), 2,89 (Qut, 2H, J=6.4 Hz), 1,96 (INM. kV, 2H, J=7,0 and 6.7 Hz), 2,86 (c, 3H).++-
834N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-[3-(N-methylsulfonylamino)propyl]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 10.74(s, 1H), 10,24(s, 1H), 9,98(s, 1H), 8,21(d, 1H, J=4.3 Hz), to 7.93(s, 1H), of 7.90(s, 1H), to 7.61(d, 1H, J=8,8 Hz), 7,38(DD, 1H, J=1.8 and 9.1 Hz), 7,22(DD, 1H, J=a 1.8 and 8.8 Hz), 7,17(s, 1H), 7,09(ISCT, 1H, J=5.3 Hz), 6.89 in (d, 1H, J=8,8 Hz), and 4.40 (t, 2H, J=7.0 Hz), 2.91 in (INM. cut, 2H, J=6,7 Hz), 2,86 (c, 3H),1,98 (INM. kV, 2H, J=6,7 Hz), 1,37 (c, 6H).-+-
835(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[1-(3-(N-methylsulfonylamino)propyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.80(s, 1H), 10,42(s, 1H), of 10.25(s, 1H), 9,98(s, 1H), they were 8.22(d, 1H, J=4.9 Hz), 7,92(s, 1H), of 7.90(d, 1H, J=1.5 Hz), to 7.64(d, 1H, J=8,8 Hz), 7,38(DD, 1H, J=2.0 and 9.1 Hz), 7.24 to 7,19(m, 3H), to 7.09(t, 1H, J=5.3 Hz), 6,91(d, 1H, J=8,8 Hz)and 4.65 (CVT, H, J= 6,7 Hz)to 4.41 (t, 2H, J=7.0 Hz), 2,92 (INM. cut, 2H, J=6,7 Hz), 2,86 (c, 3H), 2.00 (evens INM. kV, 2H, J=6,7 Hz)of 1.40 (d, 3H, J=6,7 Hz).++-
836N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[1-[3-(N-methylsulfonylamino)propyl]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 11.11(s, 1H), 9,25(s, 1H), 9,24(s, 1H), 8,11(d, 1H, J=3.0 Hz), 8,07(s, 1H), a 7.85(s, 1H), 7,58(d, 1H, J=8.5 Hz), 7,54(d, 1H, J=9.1 Hz), of 7.48(d, 1H, J=9.1 Hz), was 7.36(d, 1H, J=8.5 Hz), 7,06(t, 1H, J=6,7 Hz), 4,39(t, 2H, J=6,7 Hz), 2,93 (Qut, 2H, J=6,7 Hz), 2,85 (c, 3H), 1,98 (INM. kV, 2H, J=6,7 Hz), 1,42 (c, 6H).++-
837N2-(3-Amino-1-methylindol-5-yl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,17(s, 1H), 10,22(s, 1H), 10,13(s, 1H), of 8.25(d, 1H, J=4.4 Hz), 7,92(s, 1H), 7,58(d, 1H, J=9.1 Hz), 7,50(d, 1H, J=9.1 Hz), 7,34(d, 1H, J=8.5 Hz), 3,86(s, 3H), of 1.39(s, 3H).++
838N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(3-hydroxypropyl)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,22(s, 1H), 10,22(s, 1H), to 10.09(s, 1H), of 8.25(d, 1H, J=4.4 Hz), of 7.90(s, 2H), EUR 7.57(d, 1H, J=9.3 Hz), 7,41-7,35(m, 3H), and 4.40(t, 2H, J=6,7 Hz), the 3.35(t, 2H, J=6.4 Hz), 1.93 and(ISCCP, 2H, J=6,7 Hz)of 1.40(s, 6H).++
839N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(3-methoxypropyl)indazol-6-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,10(s, 1H), 9,46(s, 1H), 9,27(s, 1H), 8,19(d, 1H, J=3.5 Hz), 8,01(s, 1H), 7,87(s, 1H), 7,65(d, 1H, J=8.5 Hz), 7,54(d, 1H, J=8,8 Hz), 7,35(d, 1H, J=8.5 Hz), 7,29(d, 1H, J=8,8 Hz), 4,19(t, 2H, J=6,7 Hz), and 3.16(t, 2H, J=6.4 Hz), 3,13 (c, 3H), 1,94 (INM. kV, 2H, J=6,7 Hz), 1,42 (c, 3H).++
840N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-[3-(N-triftormetilfullerenov)propyl]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d for 9.47( users, 1H), 9.28 are(s, 1H), 9,17(s, 1H), 8,07(d, 1H, J=3.8 Hz), of 8.04(s, 1H), to 7.84(s, 1H), 7,79(d, 1H, J=2.6 Hz), to 7.64(DD, 1H, J=2.3 and 9.1 Hz), 7,52(d, 1H, J=8,8 Hz), 7,49(d, 1H, J=9.1 Hz), 7,07(d, 1H, J=8,8 Hz), of 4.45 (t, 2H, J=7.0 Hz), 3,82 (c, 3H), 3,19 (t, 2H, J=7.0 Hz), 2.06 to (INM. kV, 2H, J=7,0 Hz). +
841N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-[3-(N-triftormetilfullerenov)propyl]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,48(s, 1H), 10,28(s, 1H), of 9.55(t, 1H, J=5,2 Hz), 8,32(d, 1H, J=4.9 Hz), 8,00(d, 1H, J=2.0 Hz), 7,98(s, 1H), 7,85-7,81(m, 1H), 7,70-the 7.65(m, 2H), 7,52(d, 1H, J=8,8 Hz), 7,42(DD, 1H, J=2.0 and 9.1 Hz), of 4.45(t, 2H, J=6,7 Hz), 3,19 (INM. cut, 2H, J=6,7 Hz), 2.06 to (INM. kV, 2H, J=6,7 Hz).+
842N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-[3-(N-triftormetilfullerenov)propyl]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d as 10.63(s, 1H), 9,46(users, 1H), 9.28 are(s, 1H), 9,06(s, 1H), 8,12(s, 1H), with 8.05(d, 1H, J=3.8 Hz), 7,80(s, 1H), 7,47(iscd, 2H, J=9.1 Hz), 7,29(DD, 1H, J=a 2.0 and 8.8 Hz), 7,20(d, 1H, J=2.0 Hz), 6,89(d, 1H, J=8,8 Hz), 4,37 t, 2H, J=6,7 Hz)and 3.15 (m, 2H), 2,02 (INM. kV, 2H, J=6,7 Hz), 1.39 in (c, 6H).+
843(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[1-[3-(N-triftormetilfullerenov)propyl]indazol-5-yl]-2,4-pyrimidinediamine1H AMTSO-d6): d a 10.74(s, 1H), 9,88(s, 1H), 9,68(s, 1H), 9,49(t, 1H, J=6,7 Hz), 8,13(d, 1H, J=4,7 Hz), 8,01(s, 1H), 7,87(s, 1H), 7,56(d, 1H, J=9.1 Hz), the 7.43(d, 1H, J=9.1 Hz), 7,26(d, 1H, J=8.5 Hz), 7,21(s, 1H), 6.90 to(d, 1H, J=8.5 Hz), with 4.64 (Qut, 1H, J=6,7 Hz), and 4.40 (t, 2H, J=6,7 Hz), 3,17 (Qut, 2H, J=6,77 Hz), 2,03 (INM. kV, 2H, J=6,7 Hz), USD 1.43 (d, 3H, J=6,7 Hz).+
844N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[1-[3-(N-triftormetilfullerenov)propyl]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,10(s, 1H), 9,46(users, 1H), 9,23(s, 1H), 9,19(s, 1H), 8,11(DD, 1H, J=0.9 and 3.5 Hz), 8,07(s, 1H), 7,86(s, 1H), to 7.59(d, 1H, J=8.5 Hz), 7,53(d, 1H, J=9.1 Hz), 7,49(d, 1H, J=8,8 Hz), to 7.35(d, 1H, J=8.5 Hz), 4,39(t, 2H, J=7.0 Hz), 3,17 (INM. cut, 2H, J=7.0 Hz), 2,03 (INM. kV, 2H, J=7.0 Hz), 1,42 (c, 6H).-
845N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(2-methyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 11.11(s, 1H), 9,68(s, 1H), 9,42(s, 1H), to 8.20(d, 1H, J= 3.5 Hz), 8,13(s, 1H), 7,73(DD, 1H, J=1.8 and 9.1 Hz), 7,63(d, 1H, J=8.5 Hz), EUR 7.57(d, 1H, J=9.1 Hz), 7,39(d, 1H, J=8.5 Hz), 2,73(s, 3H), of 1.42(s, 6H).+++
846N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(2-trifluoromethyl-1H-benzimidazole-5-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 13.56MHz(users, 1H), 11,07(s, 1H), 9,43(s, 1H), 9,20(s, 1H), 8,16(d, 1H, J=3.5 Hz), 8,13(s, 1H), 7,73(DD, 1H, J=1.8 and 9.1 Hz), to 7.61(d, 1H, J=8.5 Hz), 7,55(d, 1H, J=9.1 Hz), was 7.36(d, 1H, J=8.5 Hz), of 1.42(s, 6H).+++
847N4-(3-Chloro-4-methoxyphenyl)-N2-[1-(3-(diethylphosphonate)propyl]indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,27(s, 1H), 9,16(s, 1H), 8,07(d, 1H, J=3.5 Hz), 8,03(s, 1H), 7,82(s, 1H), 7,79(d, 1H, J=2.3 Hz), the 7.65(DD, 1H, J=2.3 and 8.5 Hz), 7,53(d, 1H, J=8.5 Hz), 7,47(d, 1H, J=9.1 Hz), 7,08(d, 1H, J=9.1 Hz), 4,91(dt, 1H, JHH=6.7 and J2PH =to 11.0 Hz), 4,35 (t, 2H, J=6,7 Hz), 3,84 (INM. cut, 4H, JHH=6.7 and J3PH=to 11.0 Hz), 3,84 (c, 3H), by 2.73 (m, 2H), 1,92 (INM. kV, 2H, J=6,7 Hz)and 1.15 (t, 6H, J=7,0 Hz).+
848N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-evalidator)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,42(s, 1H), 10,29(s, 1H), compared to 8.26(d, 1H, J=4.9 Hz), to 7.93(s, 1H), 7,83(s, 1H), 7,74(s, 1H), 7.62mm(d, 1H, J=8,8 Hz), 7,55-7,47(m, 2H), 7,39(d, 1H, J=9.1 Hz), to 7.09(d, 1H, J=8,8 Hz), of 4.35(t, 2H, J=7.0 Hz), 3,82(s, 3H), 3,06 (INM. cut, 2H, J=6.4 Hz), 1,94 (ISCCP, 2H, J=6,7 Hz), 1.06 a (c, 9H).+
849N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(3-evalidator)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.55(s, 1H), 9.28 are(s, 1H), 8,15(DD, 1H, J=1,2 and 3.7 Hz), of 8.09(d, 1H, J=1.5 Hz), 8,00(s, 1H), 7,87(s, 1H), 7,79(DD, 1H, J=1.8 and 9.1 Hz), 7,54-7,44(m, 4H), to 4.33(t, 2H, J=6,7 Hz), 3.04 from(cut, 2H, J=6.4 Hz), 1,94(ISCCP, 2H, J=6,7 Hz), 1.06 a (c, 9H).+
850N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(3-evalidator)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 10.74(s, 1H), of 10.21(s, 1H), of 9.89(s, 1H), 8,18(d, 1H, J=4.4 Hz), to 7.93(s, 1H), 7,88(s, 1H), 7,56(d, 1H, J=8.5 Hz), 7,46(t, 1H, J=5.6 Hz), 7,37(d, 1H, J=9.1 Hz), of 7.23(d, 1H, J=9.1 Hz), 7,17(s, 1H), to 6.88(d, 1H, J=8, 8 Hz), to 4.33 (t, 2H, J=6.4 Hz), 3,02 (Qut, 2H, J=6,7 Hz), 1,92 (INM. kV, 2H, J=6,7 Hz), 1,37 (c, 6H), 1.05 of (c, 9H).+
8515-fluoro-(S)-N4-(2-methyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-N2-[1-(3-evalidator)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,80(s, 1H), 10,42(s, 1H, 10,28(s, 1H), they were 8.22(d, 1H, J=4.4 Hz), of 7.90(s, 2H), to 7.59(d, 1H, J=8,8 Hz), 7,47(m, 1H), 7,38(d, 1H, J=8,8 Hz), 7,22(iscd, 2H, J=8,8 Hz)6,91(d, 1H, J=8,8 Hz), with 4.64(Qut, 1H, J=6,7 Hz), 4,34 (t, 2H, J=6,7 Hz), 3,03 (Qut, 2H, J=6,7 Hz), 1,95 (INM. kV, 2H, J=7,0 Hz)of 1.40 (d, 3H, J=6,7 Hz), 1,05 (c, 9H).+
852N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(3-evalidator)indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,10(s, 1H), which 9.22(s, 1H), 9,18(s, 1H), 8,12(d, 1H, J=3.5 Hz), to 7.84(s, 1H), 7,82(s, 1H), to 7.59(d, 1H, J=8,8 Hz), of 7.48-the 7.43(m, 3H), of 7.36(d, 1H, J=8.5 Hz), 4,32(t, 2H, J=6,7 Hz), 3,02(Qut, 2H, J=6,7 Hz), 1,92(ISCCP, 2H, J=6,7 Hz), 1,42 (c, 6H), 1.05 of (c, 9H).+
853N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-[3-(N-Succinimidyl)]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9.28 are(s, 1H), 9,17(s, 1H), 8,07(d, 1H, J=3.5 Hz), 7,82(s, 1H), 7,78(d, 1H, J=2.0 Hz), 7,66(DD, 1H, J=2.0 and 8.5 Hz), 7,52(d, 1H, J=9.1 Hz), 7,46(d, 1H, J=9.1 Hz), to 7.09(d, 1H, J=8,5 Hz)to 4.33(t, 2H, J=6.3 Hz), 3,84 (c, 3H), 3,38 (t, 2H, J=6.3 Hz), 2,54 (c, 2H), 2,48 (c, 2H), 2,02 (q, 2H, J=6.3 Hz).++
854 N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-[3-(N-Succinimidyl)]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.55(s, 1H), 9.28 are(s, 1H), 8,16(d, 1H, J=3.5 Hz), 8,08(d, 1H, J=2.3 Hz), 8,01(s, 1H), 7,88(s, 1H), 7,80(DD, 1H, J=2,3 and 8.8 Hz), 7,56(d, 1H, J=8,8 Hz), 7,51-7,46(m, 2H), 4,35(t, 2H, J=6,7 Hz), 3,40(t, 2H, J=7.0 Hz), 2,55 (c, 2H), 2,48 (c, 2H), 2,03 (INM. kV, 2H, J=7,0 Hz).+-
855N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-[3-(N-Succinimidyl)]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.73(s, 1H), 10,38(s, 1H), of 10.25(s, 1H), 8,18(d, 1H, J=3,9 Hz), the 7.85(s, 1H), 7,83(s, 1H), 7,56(d,1H, J=9.1 Hz), 7,32(d, 1H, J=8,8 Hz), 7,14(d, 2H, J=9.1 Hz), at 6.84(d, 1H, J=8,8 Hz), 4,30(t, 2H, J=7,0 Hz)to 3.34(t, 2H, J=6,7 Hz), 2,50 (c, 2H), 2,42 (c, 2H), 1,98 (INM. kV, 2H, J=7.0 Hz), 1,31 (c, 6H).++
856(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[1-[3-(N-Succinimidyl)]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d was 10.82(s, 1H), 10,52(s, 1H), 10,42(s, 1H), 8,24(d, 1H, J=4.9 Hz), 7,92(s, 1H), 7,87(s, 1H), 7,63(d,1H, J=8,8 Hz), 7,37(DD, 1H, J=1,0 and 8.8 Hz), 7,20(d, 2H, J=8,8 Hz)6,91(d, 1H, J=9.1 Hz)and 4.65(Qut, 1H, J=6,7 Hz), 4,36 (t, 2H, J=6,7 Hz), 3,39 (t, 2H, J=6,7 Hz), 2,55 (c, 2H), 2,48 (c, 2H), 2,01 (INM. kV, 2H, J=6,7 Hz), 139 (d, 3H, J=6,7 Hz).++
857N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[1-[3-(N-Succinimidyl)]indazol-5-yl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,10(s, 1H), 9,23(s, 1H), 9,19(s, 1H), 8,12(d, 1H, J=3.5 Hz), of 8.06(s, 1H), EUR 7.57(d, 1H, J=8,8 Hz), 7,53-7,46(m, 2H), was 7.36(d, 1H, J=8,8 Hz)to 4.33(t, 2H, J=7.0 Hz), 3,39(t, 2H, J=6,7 Hz)to 2.54(s, 2H), 2,48(s, 2H), 2,02 (INM. kV, 2H, J=7.0 Hz), 1,42 (c, 6H).++
858N4-(3-Chloro-4-methoxyphenyl)-N2-[1-[3-(2,6-dioxopiperidin]propyl)indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,26(s, 1H), 10,08(s, 1H), they were 8.22(d, 1H, J=4.3 Hz), 7,92(s, 1H), a 7.85(s, 1H), 7,74(d,1H, J=2.0 Hz), a 7.62(d, 1H, J=8,8 Hz), EUR 7.57(DD, 1H, J=2,3 and 8.8 Hz), 7,39(DD, 1H, J=2.0 and 8.3 in Hz), to 7.09(d, 1H, J=8,8 Hz), 4,35(t, 2H, J=7.0 Hz), 3,83 (c, 3H), to 3.67 (t, 2H, J=7.0 Hz), 2,53 (t, 4H, J=6,7 Hz), 1,96 (INM. kV, 2H, J=7.0 Hz), 1,76 (q, 2H, J=6,7 Hz).++
859N4-(3,4-Dichlorophenyl)-N2-[1-[3-(2,6-dioxopiperidin)propyl]indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DM what About-d6): d of 10.05(s, 1H), made up 9.77(s,1H), 8,23(d, 1H, J=5,1 Hz), 8,03(s, 1H), 7,92(s, 1H), to $ 7.91(s, 1H), 7,73(d, 1H, J=8,8 Hz), to 7.61(d, 1H, J=8,8 Hz), 7,51(d,1H, J=8,8 Hz), 7,44(d, 1H, J=8,8 Hz), 4,35(t, 2H, J=6,7 Hz), to 3.67(t, 2H, J=6,7 Hz), 2,53 (t, 4H, J=6.4 Hz), 1,97 (q, 2H, J=6.4 Hz), 1,75 (INM. kV, 2H, J=6,7 Hz).++
860N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-N2-[1-[3-(2,6-dioxopiperidin]propyl)indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 10.76(s, 1H), 10,34(s, 1H), 10,16(s, 1H), 8,21(d, 1H, J=4.3 Hz), 7,89(s, 2H), to 7.59(d, 1H, J=8.5 Hz), 7,37(DD, 1H, J=1.5 and 8.5 Hz), 7,21(d, 1H, J=8,8 Hz), 7,19(s, 1H), to 6.88(d, 1H, J=8,8 Hz), 4,35(t, 2H, J=7.0 Hz), 3,66 (t, 2H, J=7.0 Hz), 2,53 (t, 4H, J=7.0 Hz), 1,95 (q, 2H, J=7.0 Hz), 1,76 (INM. kV, 2H, J=7.0 Hz), 1,36 (c, 6H).++
861(S)-N2-[1-[3-(2,6-Dioxopiperidin]propyl)indazol-5-yl]-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,78(s, 1H), 10,49(s, 1H), 10,44(s, 1H), 8,21(d, 1H, J=4.9 Hz), the 7.85(s, 1H), 7,82(s, 1H), 7,56(d, 1H, J=8,8 Hz), 7,31(d, 1H, J=8,8 Hz), 7,17(s, 1H), 7,16(d, 1H, J=8,8 Hz), 6,86(d, 1H, J=8,8 Hz), 4,59(Qut, 1H, J=6,7 Hz), the 4.29 (t, 2H, J=6,7 Hz), 3,61 (t, 2H, J=7.0 Hz), 2,47 (t, 4H, J=7.0 Hz), 1,90 (q, 2H, J=7.0 Hz), 1,71 (INM. kV, 2H, J=6,7 Hz)of 1.35 (d, 3H, J=6,7 Hz).+ +
862N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-[1-[3-(2,6-dioxopiperidin]propyl)indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,10(s, 1H), which 9.22(s, 1H), 9,18(s, 1H), 8,12(d, 1H, J=3.2 Hz), with 8.05(s, 1H), to 7.84(s, 1H), 7,58(d, 1H, J=8,2 Hz), of 7.48(s, 2H), was 7.36(d, 1H, J=8,2 Hz), 4,32(t, 2H, J=7,3 Hz), 3,66(t, 2H, J=7,3 Hz), a 2.45(t, 2H, J=7,3 =6,7 Hz), the 4.29 (t, 2H, J=6,7 Hz), 3,61 (t, 2H, J=7.0 Hz), 2,47 (t, 4H, J=7.0 Hz), 1,90 (q, 2H, J=7.0 Hz), 1,71 (INM. kV, 2H, J=6,7 Hz)of 1.35 (d, 3H, J=6,7 Hz).++
863N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-trifluoromethyl-1H-benzimidazole-5-yl)-2,4-pyrimidinediamine cleaners containing hydrochloride salt1H NMR(DMSO-d6): d 10,33(s, 1H), 10,23(s, 1H), 8,32(d, 1H, J=4,7 Hz), 8,03(d, 1H, J=2.0 Hz), of 7.90(s, 1H), 7,74(d, 1H, J=2.0 Hz), 7,69(d, 1H, J=8,8 Hz), 7,51(d, 1H, J=8,8 Hz), was 7.45(DD, 1H, J=2.0 and 8,8 Hz).++
864N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-trifluoromethyl-1H-benzimidazole-5-yl)-2,4-pyrimidinediamine salt econsultancy acid1H NMR(DMSO-d6): d 10,11(s, 1H), 9,92(s, 1H), 8,27(d, 1H, J=4.4 Hz), of 8.06(d, 1H, J=2.0 Hz), and 7.4(s, 1H), 7,76(d, 1H, J=2.0 Hz), to 7.67(d, 1H, J=8,8 Hz), 7,51(d, 1H, J=8,8 Hz), 7,41(DD, 1H, J=a 2.0 and 8.8 Hz), 2,42(Qut, 2H, J=7,3 Hz)of 1.05 (t, 3H, J=7,3 Hz).-+
865N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-trifluoromethyl-1H-benzimidazole-5-yl)-2,4-pyrimidinediamine salt benzosulfimide acid1H NMR(DMSO-d6): d of 10.25(s, 1H), 10,04(s, 1H), 8,29(d, 1H, J=4.4 Hz), 8,03(s, 1H), to $ 7.91(s, 1H), 7,73-7,26(m, 2H), 7,58-the 7.43(m, 4H), 7,29-7,27(m, 3H).-+
866N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-trifluoromethyl-1H-benzimidazole-5-yl)-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR(DMSO-d6): d 10,30(s, 1H), 10,08(s, 1H), 8.30 to(d, 1H, J=4,7 Hz), 8,03(d, 1H, J=2.0 Hz), of 7.90(s, 1H), 7,71(d, 2H, J=8,8 Hz), 7,51(d, 1H, J=8,8 Hz), 7,47-the 7.43(m, 3H), 7,10(d, 2H, J=8,8 Hz), 2.26 and(s, 3H).-+
867N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-methyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine salt benzosulfimide acid1H NMR(DMSO-d6): d 9,77(s, 1H), 9,74(s, 1H), of 8.25(d, 1H, J=3.8 Hz), 8,14(who, 1H, J=2.3 Hz), to 8.12(s, 1H), 7,81(DD, 1H, J=2,3 and 8.8 Hz), 7,66(d, 2H, J=9.1 Hz), to 7.59-7,52(m, 3H), 7,33-7,27(m, 3H), 2,74(s, 3H).++
868N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-methyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR(DMSO-d6): d 9,78(s, 1H), 9,74(s, 1H), of 8.25(d, 1H, J=3.8 Hz), 8,14(d, 1H, J=2.3 Hz), to 8.12(s, 1H), 7,81(DD, 1H, J=2,3 and 8.8 Hz), 7,66(d, 2H, J=9.1 Hz), 7,54(d, 1H, J=8,8 Hz), 7,46(d, 2H, J=8,2 Hz), 7,10(d, 2H, J=8,2 Hz), 2, 74 (c, 3H).++
869N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-methyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine cleaners containing hydrochloride salt1H NMR(DMSO-d6): d to 9.93(s, 2H), 8,28(d, 1H, J=3.8 Hz), to 8.12(d, 1H, J=2.3 Hz), 8,07(s, 1H), 7,81(DD, 1H, J=a 1.8 and 8.8 Hz), 7,66(d, 2H, J=8,8 Hz), 7,56(d, 1H, J=8,8 Hz)of 2.75(s, 3H).++
870N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(2-methyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamine salt econsultancy acid1H NMR(DMSO-d6): d of 9.75(s, 2H), 9,72(s, 1H), 8,24(d, 1H, J=3.8 Hz), 8,14(d, 1H, J=20 Hz), to 8.12(s, 1H), 7,82(d, 1H, J= 8,8 Hz), 7,66(d, 2H, J=8.5 Hz), 7,53(d, 1H, J=8,8 Hz), is 2.74(s, 3H), 2.40 a(Qut, 2H, J=7,3 Hz)of 1.05(t, 3H, J=7,3 Hz).++
871N4-(3-Chloro-4-methoxyphenyl)-N2-[1-(3-ethoxypropan)indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,37(s, 1H), 10,23(s, 1H), of 8.25(d, 1H, J=5.3 Hz), 7,92(s, 1H), 7,83(s, 1H), 7,74(d, 1H, J=2.6 Hz), to 7.59(d, H, J=8,8 Hz), 7,53(DD, 1H, J=2.3 and 8.5 Hz), 7,38(DD, 1H, J=a 1.8 and 8.8 Hz), to 7.09(d, 1H, J=9.1 Hz), and 4.40(t, 2H, J=6,7 Hz), 3,83 (c, 3H), 3,31 (Qut, 2H, J=6,7 Hz), 3,26 (t, 2H, J=6,7 Hz), 2,01 (INM. kV, 2H, J=6,7 Hz)of 1.06 (t, 3H, J=6,7 Hz).++
872N4-(3,4-Dichlorophenyl)-N2-[1-(3-ethoxypropan)indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,27(s, 1H), 10,02(s, 1H), 8,28(d, 1H, J=4,7 Hz), 8,02(d, 1H, J=2.3 Hz), 7,95(s, 1H), 7,87(s, 1H), 7,68(d, 1H, J=8,8 Hz), 7,60(d, 1H, J=8,8 Hz), 7,51(d,1H, J=8,8 Hz), 7,42(DD, 1H, J=2,3 and 8.8 Hz), to 4.41(t, 2H, J=6.4 Hz), 3,32 (Qut, 2H, J=6,7 Hz), with 3.27 (t, 2H, J=6.4 Hz), 2,02 (q, 2H, J=6.4 Hz), with 1.07 (t, 3H, J=6,7 Hz).+
873N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-N2-[1-(3-e is oksipropil)indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d of 10.76(s, 1H), 10,36(s, 1H), 10,19(s, 1H), they were 8.22(d, 1H, J=5.3 Hz), of 7.90(s, 2H), 7,55(d, 1H, J=9.1 Hz), 7,37(DD, 1H, J=a 1.8 and 8.8 Hz), 7,20(d, 1H, J=8,8 Hz), 7,18(s, 1H), 6.87 in(d, 1H, J=8,8 Hz), 4,39(t, 2H, J=6,7 Hz)and 3.31 (Qut, 2H, J=7,0 Hz)at 3.25 (t, 2H, J=6,7 Hz), 1,99 (INM. kV, 2H, J=6,7 Hz), 1,36 (c, 6H), of 1.07 (t, 3H, J=7,0 Hz).++
874(S)-N2-[1-(3-Ethoxypropan)indazol-5-yl]-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,79(s, 1H), the 10.40(s, 1H), 10,24(s, 1H), they were 8.22(d, 1H, J=5.3 Hz), of 7.90(d, 1H, J=1.8 Hz), 7,88(s, 1H), EUR 7.57(d, 1H, J=9.1 Hz), 7,37(DD, 1H, J=1.8 and 9.1 Hz), 7,22(DD, 2H, J=1.8 and 8.5 Hz), 6,89(d, 1H, J=8.5 Hz)and 4.65 (Qut, 1H, J=7,0 Hz), and 4.40 (t, 2H, J=6,7 Hz), 3,29 (Qut, 2H, J=7,0 Hz)at 3.25 (t, 2H, J=6,7 Hz), 2.00 (evens INM. kV, 2H, J=6,7 Hz)of 1.40 (d, 3H, J=7.0 Hz), with 1.07 (t, 3H, J=7,0 Hz).++
875N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-[1-(3-ethoxypropan)indazol-5-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 11,10(s, 1H), which 9.22(s, 1H), 9,19(s, 1H), 8,11(d, 1H, J=3.5 Hz), with 8.05(s, 1H), to 7.84(s, 1H), 7,58(d, 1H, J=8.5 Hz), 7,42(d, 2H, J=8,8 Hz), 7,35(d, 1H, J=8.5 Hz), 4,37(t, 2H, J=of 6.7 Hz), 3,32(Qut, 2H, J=7.0 Hz), or 3.28(t, 2H, J=6,7 Hz), 2,02 (INM. kV, 2H, J=6,7 Hz), 1,42 (c, 6H), of 1.07 (t, 3H, J=7,0 Hz). ++
876N4-(2-Chloro-3-methoxyphenyl-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,32(s, 1H), 9,63(s, 1H), 8,19(d, 1H, J=4,1 Hz), of 8.06(d, 1H, J=8.5 Hz), 7,52(d, 1H, J=8.5 Hz), 6,91(s, 2H), 3,88(s, 3H), of 3.64(s, 6H), 3,61(s, 3H).++
877N4-(2-Chloro-3-methoxyphenyl-6-yl)-N2-(3,4-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,84(s, 1H), 9,23(s, 1H), 8,15(d, 1H, J=8,8 Hz)to 8.14(d, 1H, J=3.5 Hz), 7,55(d, 1H, J=9.1 Hz), 6.90 to(d, 1H, J=2.3 Hz), between 6.08(d, 2H, J=2.3 Hz), 3,88(s, 3H), of 3.65(s, 3H).+
878N2-(3-Chloro-4-methoxyphenyl)-N4-(2-chloro-3-methoxyphenyl-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,83(s, 1H), 9,26(s, 1H), 8,14(d, 1H, J=3.5 Hz), 8,01(d, 1H, J=9.1 Hz), 7,80(d, 1H, J=2.6 Hz), to 7.59(d, 1H, J=9.1 Hz), the 7.43(DD, 1H, J=2.6 and 9.1 Hz), 7,03(d, 1H, J=9.1 Hz), 3,88(, 3H), of 3.78(s, 3H).-
879 N4-(2-Chloro-3-methoxyphenyl-6-yl)-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,79(s, 1H), 9.15, with(s, 1H), 8,13(d, 1H, J=3.5 Hz), 8,08(DD, 1H, J=2,3 and 8.8 Hz), EUR 7.57(d, 1H, J=8,8 Hz), 7,22(s, 2H), 6,53(s, 1H), 3,82(s, 3H), 2,19(s, 6H). H+).++
880N4-(2-Chloro-3-methoxyphenyl-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,84(s, 1H), to 9.32(s, 1H), 8,14(d, 1H, J=3.5 Hz), to 8.12(d, 1H, J=8,8 Hz), of 7.96(Qut, 1H, J=4,7 Hz), 7,60(d, 1H, J=8,8 Hz), 7,37(ISCS, 1H), 7.23 percent(d, 1H, J=8,2 Hz), 7,13(t, 1H, J=8,2 Hz), 6,48(DD, 1H, J=2.3 and 8.2 Hz), 4,37 (c, 2H), a 3.87 (c, 3H), 2,61 (d, 3H, J=4,7 Hz).++
8812-Chloro-N4-(2-chloro-3-methoxyphenyl-6-yl)-5-fluoro-4-pyrimidinamine1H NMR(DMSO-d6): d with 8.33(d, 1H, J=8,8 Hz)to 8.12(d, 1H, J=2.3 Hz), 7,65(users, 1H), 7,38(d, 1H, J=8,8 Hz), of 3.94(s, 3H).
882N4-(2-Chloro-3-methoxyphenyl-6-yl)-5-fluoro-N2-(indazol-6-yl)-2,4-pyrimidinediamineLC/MS: time derivan the I: 10,99 min; purity: 93%; MS(mass/charge): 386(MH+).+
883N4-(2-Chloro-3-methoxyphenyl-6-yl)-5-fluoro-N2-(2-trifluoromethyl-1H-benzimidazole-5-yl)-2,4-pyrimidinediamineLC/MS: retention time: 11,74 min; purity: 97%; MS(mass/charge): 454(MH+).+
884N4-(2-Chloro-3-methoxyphenyl-6-yl)-5-fluoro-N2-(2-methyl-3H-benzimidazole-5-yl)-2,4-pyrimidinediamineLC/MS: retention time: 7,71 min; purity: 93%; MS(mass/charge): 400(MH+).+
885N4-(2-Chloro-3-methoxyphenyl-6-yl)-5-fluoro-N2-(1-methylindol-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 12,20 min; purity: 93%; MS(mass/charge): 400(MH+).+
886N4-(2-Chloro-3-methoxyphenyl-6-yl)-ftor-N2-(1-methylindol-5-yl)-2,4-pyrimidinediamine LC/MS: retention time: 10,79 min; purity: 94%; MS(mass/charge): 400(MH+).-
887N4-(2-Chloro-3-methoxyphenyl-6-yl)-5-fluoro-N2-(1-ethylindole-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 12,97 min; purity: 95%; MS(mass/charge): 414(MH+).+
888N4-(2-Chloro-3-methoxyphenyl-6-yl)-5-fluoro-N2-(1-isopropylindole-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 13,86 min; purity: 92%; MS(mass/charge): 428(MH+).+
889N4-(2-Chloro-3-methoxyphenyl-6-yl)-N2-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 11,84 min; purity: 94%; MS(mass/charge): 445(MH+).+
80 N2-[1-[3-(N-Acetylamino)propyl]indazol-5-yl]-N4-(2-chloro-3-methoxyphenyl-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 9,42 min; purity: 95%; MS(mass/charge): 485(MH+).+
891N4-(2-Chloro-3-methoxyphenyl-6-yl)-N2-[1-[3-(N-cyclopropanecarbonyl)propyl]indazol-5-yl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 10,30 min; purity: 95%; MS(mass/charge): 511(MH+).+
892N4-(2-Chloro-3-methoxyphenyl-6-yl)-5-fluoro-N2-[1-(3-evalidator)indazol-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 11,73 min; purity: 99%; MS(mass/charge): 527(MH+).+
893N4-(2-Chloro-3-methoxyphenyl-6-yl)-5-fluoro-N2-[1-[3-(N-isobutylamino)propyl]indazol-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 10,71 min; purity: 97%; MS(mass/C is a number): 514(MH +).+
894N4-(3,4-Dichlorophenyl)-N2-(1,2-dimethylbenzimidazole-5-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 9,44 min; purity: 100%; MS(mass/charge): 418(MH+).+
895N4-(3-Chloro-4-methoxyphenyl)-N2-(1,2-dimethylbenzimidazole-5-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 7,66 min; purity: 96%; MS(mass/charge): 413(MH+).+
896N2-(1,2-Dimethylbenzimidazole-5-yl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 7,09 min; purity: 99%; MS(mass/charge): 448(MH+).++
897(S)-N2-(1,2-Dimethylbenzimidazole-5-yl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-Ben is[1,4]oxazin-6-yl)-2,4-pyrimidinediamine LC/MS: retention time: 6,52 min; purity: 97%; MS(mass/charge): 434(MH+).+++
898N2-(1,2-Dimethylbenzimidazole-5-yl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: a 7.85 min; purity: 91%; MS(mass/charge): 449(MH+).+++
899N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(2-hydroxyethyl)-2-methylbenzimidazole-5-yl)-2,4-pyrimidinediamineLC/MS: retention time: 8,77 min; purity: 97%; MS(mass/charge): 448(MH+).++
900N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(2-hydroxyethyl)-2-methylbenzimidazole-5-yl)-2,4-pyrimidinediamineLC/MS: retention time: 7,06 min; purity: 93%; MS(mass/charge): 443(MH+).+
901N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(2-hydroxyethyl)-2-methylbenzimidazole-5-yl)-2,4-pyrimidinediamineLC/MS: retention time: 6,50 min; purity: 97%; MS(mass/charge): 478(MH+).++
902(S)-5-fluoro-N2-[1-(2-hydroxyethyl)-2-methylbenzimidazole-5-yl)-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 5,99 min; purity: 94%; MS(mass/charge): 464(MH+).++
903N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(2-hydroxyethyl)-2-methylbenzimidazole-5-yl)-2,4-pyrimidinediamineLC/MS: retention time: 6,89 min; purity: 97%; MS(mass/charge): 479(MH+).++
904N4-(3,4-Dichlorophenyl)-N2-(2,3-dihydro-1-methyl-2-oxopentanoate-5-yl)-5-fluoro-2,4-pyrimidinediamine LC/MS: retention time: 10,32 min; purity: 100%; MS(mass/charge): 420(MH+).--
905N4-(3-Chloro-4-methoxyphenyl)-N2-(2,3-dihydro-1-methyl-2-oxopentanoate-5-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 8,24 min; purity: 96%; MS(mass/charge): 415(MH+).++
906N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-N2-(2,3-dihydro-1-methyl-2-oxopentanoate-5-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 7,53 min; purity: 97%; MS(mass/charge): 450(MH+).++
907(S)-N2-(2,3-Dihydro-1-methyl-2-oxopentanoate-5-yl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 7,00 min; purity: 98%; MS(mass/charge): 436(MH+).++
908N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(2,3-dihydro-1-methyl-2-oxopentanoate-5-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 8,19 min; purity: 94%; MS(mass/charge): 451(MH+).++
9095-fluoro-N2-(2-methyl-3H-benzimidazole-5-yl)-N4-(2-methyl-1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 7,11 min; purity: 94%; MS(mass/charge): 468(MH+).++
9105-fluoro-N4-(2-methyl-1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-N2-(2-trifluoromethyl-1H-benzimidazole-5-yl)-2,4-pyrimidinediamineLC/MS: retention time: 10,29 min; purity: 98%; MS(mass/charge): 521(MH+).++
911N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(1-methyl-2-triftoratsetata-5-yl)-2,4-pyrimidinediamine LC/MS: retention time: of 14.28 min; purity: 97%; MS(mass/charge): 472(MH+).+
912N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(1-methyl-2-triftoratsetata-5-yl)-2,4-pyrimidinediamineLC/MS: retention time: 11,38 min; purity: 91%; MS(mass/charge): 467(MH+).+
913N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-N2-(1-methyl-2-triftoratsetata-5-yl)-2,4-pyrimidinediamineLC/MS: retention time: of 10.21 min; purity: 94%; MS(mass/charge): 502(MH+).+
914(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-(1-methyl-2-triftoratsetata-5-yl)-2,4-pyrimidinediamineLC/MS: retention time: 9,66 min; purity: 93%; MS(mass/charge): 488(MH+).+
915N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(1-methyl-2-triftoratsetata-5-yl)-2,4-pyrimidinediamineLC/MS: retention time: 11,48 min; purity: 91%; MS(mass/charge): 503(MH+).+
916N4-(3,4-Dichlorophenyl)-5-fluoro-[1-(2-hydroxyethyl)-2-triftoratsetata-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 12,15 min; purity: 96%; MS(mass/charge): 502(MH+).+
917N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-[1-(2-hydroxyethyl)-2-triftoratsetata-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 9,90 min; purity: 94%; MS(mass/charge): 497(MH+).+
918N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-[1-(2-hydroxyethyl)-2-triftoratsetata-5-yl]-2,4-pyrimidinediamine LC/MS: retention time: the remaining 9.08 min; purity: 96%; MS(mass/charge): 532(MH+).++
919(S)-5-fluoro-[1-(2-hydroxyethyl)-2-triftoratsetata-5-yl]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 8,67 min; purity: 92%; MS(mass/charge): 518(MH+).++
920N4-(3,4-Dichlorophenyl)-5-fluoro-[1-(2-hydroxymethyl)-2-triftoratsetata-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 14,96 min; purity: 97%; MS(mass/charge): 486(MH+).++
921N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-[1-(2-hydroxymethyl)-2-triftoratsetata-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 12,21 min; purity: 98%; MS(mass/charge): 481(MH+).++
922N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-[1-(2-hydroxymethyl)-2-triftoratsetata-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: of 10.93 min; purity: 96%; MS(mass/charge): 516(MH+).+
923(S)-5-fluoro-[1-(2-hydroxymethyl)-2-triftoratsetata-5-yl]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 10,43 min; purity: 92%; MS(mass/charge): 502(MH+).+
924N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-[1-(2-hydroxymethyl)-2-triftoratsetata-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 12,25 min; purity: 98%; MS(mass/charge): 517(MH+).+
925N2-(1,2-Benzisoxazol-5-yl)-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamine/td> LC/MS: retention time: 9,63 min; purity: 100%; MS(mass/charge): 386(MH+).+
926N2-(1,2-Benzisoxazol-5-yl)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 8,48 min; purity: 100%; MS(mass/charge): 421(MH+).+
927(S)-N2-(1,2-Benzisoxazol-5-yl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 8,11 min; purity: 100%; MS(mass/charge): 407(MH+).+
928N2-(1,2-Benzisoxazol-5-yl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: to 9.57 min; purity: 100%; MS(mass/charge): 422(MH+).+
929Racemic-N2-(1,2-benzisoxazol-5-yl)-5-fluoro-(2-methyl-1,1,3-trioxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: RS 9.69 min; purity: 95%; MS(mass/charge): 455(MH+).+
930N2-(1,2-Benzisoxazol-5-yl)-N4-(2,2-dimethyl-1,1,3-trioxo-4H-benzo[1,4]thiazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 10,13 min; purity: 97%; MS(mass/charge): 470(MH+).+
931Racemic-N2-(1,2-benzisoxazol-5-yl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]thiazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: of 9.21 min; purity: 96%; MS(mass/charge): 423(MH+).+
932N4-(3,4-Dichlorophenyl)-N2-(1-ethyl-2-methylbenzimidazole-5-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: to 10.09 min; purity: 99%; MS(mass/dawn is): 432(MH +).-
933N4-(3-Chloro-4-methoxyphenyl)-N2-(1-ethyl-2-methylbenzimidazole-5-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 8,64 min; purity: 92%; MS(mass/charge): 427(MH+).+
934N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-N2-(1-ethyl-2-methylbenzimidazole-5-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: to $ 7.91 min; purity: 99%; MS(mass/charge): 462(MH+).+
935(S)-N2-(1-Ethyl-2-methylbenzimidazole-5-yl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 7,72 min; purity: 95%; MS(mass/charge): 448(MH+).++
936N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,]oxazin-6-yl)-N2-(1-ethyl-2-methylbenzimidazole-5-yl)-5-fluoro-2,4-pyrimidinediamine LC/MS: retention time: 8,48 min; purity: 96%; MS(mass/charge): 463(MH+).+
937N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(3-hydroxypropyl)-2-triftoratsetata-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: of 12.33 min; purity: 97%; MS(mass/charge): 516(MH+).++
938N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-hydroxypropyl)-2-triftoratsetata-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 9,85 min; purity: 94%; MS(mass/charge): 511(MH+).+
939N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(3-hydroxypropyl)-2-triftoratsetata-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 9,04 min; purity: 96%; MS(mass/charge): 546(MH+).++
940(S)-5-fluoro-N2-[1-(3-hydroxypropyl)-2-triftoratsetata-5-yl]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 8,49 min; purity: 95%; MS(mass/charge): 532(MH+).++
941N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(3-hydroxypropyl)-2-triftoratsetata-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 9,85 min; purity: 93%; MS(mass/charge): 547(MH+).++
942N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-methyl-2-(4-morpholino)benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 9,49 min; purity: 97%; MS(mass/charge): 489(MH+).+++
943N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-methyl-2-(4-morpholino)benzimidazole-5-yl]2,4-pyrimidinediamine LC/MS: retention time: 7,79 min; purity: 93%; MS(mass/charge): 484(MH+).++
944N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-methyl-2-(4-morpholino)benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 7,20 min; purity: 99%; MS(mass/charge): 519(MH+).+++
945(S)-5-fluoro-N2-[1-methyl-2-(4-morpholino)benzimidazole-5-yl]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 6,78 min; purity: 90%; MS(mass/charge): 505(MH+).++
946N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[1-methyl-2-(4-morpholino)benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 7,86 min; purity: 96%; MS(mass/charge): 520(MH+).++
947N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-(3-hydroxypropyl)-2-methylbenzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 9,65 min; purity: 95%; MS(mass/charge): 462(MH+).+
948N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-(3-hydroxypropyl)-2-methylbenzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 8,28 min; purity: 90%; MS(mass/charge): 457(MH+).+
949N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(3-hydroxypropyl)-2-methylbenzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 7,70 min; purity: 96%; MS(mass/charge): 492(MH+).+
950(S)-5-fluoro-N2-[1-(3-hydroxypropyl)-2-methylbenzimidazole-5-yl]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimi Indiamen LC/MS: retention time: 7,22 min; purity: 90%; MS(mass/charge): 478(MH+).+
951N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[1-(3-hydroxypropyl)-2-methylbenzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 7,97 min; purity: 94%; MS(mass/charge): 493(MH+).++
952N2-[1-[3-(N-Acetylamino)propyl]-2-methylbenzimidazole-5-yl]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 7,89 min; purity: 97%; MS(mass/charge): 533(MH+).++
953N2-[1-[3-(N-Acetylamino)propyl]-2-methylbenzimidazole-5-yl]-N4-(2,2-dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 8,09 min; purity: 97%; MS(mass/charge): 534(MH+).+
954N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-methyl-2-(4-morpholinomethyl)benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 10,04 min; purity: 96%; MS(mass/charge): 503(MH+).++
955N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-methyl-2-(4-morpholinomethyl)benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 9,29 min; purity: 93%; MS(mass/charge): 498(MH+).+
956N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-methyl-2-(4-morpholinomethyl)benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 8,09 min; purity: 94%; MS(mass/charge): 533(MH+).+
957(S)-5-fluoro-N2-[1-methyl-2-(4-morpholinomethyl)benzimidazole-5-yl]-N4-(2-methyl-3-oxo-2H,4H-b is NC[1,4]oxazin-6-yl)-2,4-pyrimidinediamine LC/MS: retention time: at 7.55 min; purity: 98%; MS(mass/charge): 519(MH+).++
958N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[1-methyl-2-(4-morpholinomethyl)benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 8.34 per min; purity: 98%; MS(mass/charge): 534(MH+).+
959N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[2-(4-morpholinomethyl)-1H-benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 9,12 min; purity: 95%; MS(mass/charge): 489(MH+).+
960N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[2-(4-morpholinomethyl)-1H-benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 8,10 min; purity: 97%; MS(mass/charge): 484(MH+).+
961N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[2-(4-morpholinomethyl)-1H-benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 7,70 min; purity: 93%; MS(mass/charge): 519(MH+).++
962N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[2-(4-morpholinomethyl)-1H-benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 7,93 min; purity: 95%; MS(mass/charge): 520(MH+).++
963N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[2-methyl-1-[3-(N-methylsulfonylamino)propyl]benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 8,01 min; purity: 95%; MS(mass/charge): 569(MH+).+
964N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[2-methyl-1-[3-(N-matilal is phenylamino)propyl]benzimidazole-5-yl]-2,4-pyrimidinediamine LC/MS: retention time: at 8.36 min; purity: 95%; MS(mass/charge): 570(MH+).++
965N4-(3,4-Dichlorophenyl)-5-fluoro-N2-{1-methyl-2-[(methylsulphonyl)methyl]benzimidazole-5-yl}-2,4-pyrimidinediamineLC/MS: retention time: 10,63 min; purity: 94%; MS(mass/charge): 496(MH+).+
966N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-{1-methyl-2-[(methylsulphonyl)methyl]benzimidazole-5-yl}-2,4-pyrimidinediamineLC/MS: retention time: 9,10 min; purity: 95%; MS(mass/charge): 491(MH+).+
967N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-{1-methyl-2-[(methylsulphonyl)methyl]benzimidazole-5-yl}-2,4-pyrimidinediamineLC/MS: retention time: which 9.22 min; purity: 91%; MS(mass/charge): 525(MH+).++
968(S)-5-fluoro-N2-{1-methyl-2-[(methylsulphonyl)methyl]benzimidazole-5-yl}-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 8,62 min; purity: 91%; MS(mass/charge): 512(MH+).++
969N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-{1-methyl-2-[(methylsulphonyl)methyl]benzimidazole-5-yl}-2,4-pyrimidinediamineLC/MS: retention time: 9,14 min; purity: 94%; MS(mass/charge): 527(MH+).++
970N4-(3,4-Dichlorophenyl)-N2-[2-(N,N-diethylaminomethyl)-1-methylbenzimidazole-5-yl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 9,42 min; purity: 91%; MS(mass/charge): 489(MH+).+
971N4-(3-Chloro-4-methoxyphenyl)-N2-[2-(N,N-diethylaminomethyl is)-1-methylbenzimidazole-5-yl]-5-fluoro-2,4-pyrimidinediamine LC/MS: retention time: 7,76 min; purity: 94%; MS(mass/charge): 485(MH+).+
972N2-[2-(N,N-Diethylaminomethyl)-1-methylbenzimidazole-5-yl]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 7,56 min; purity: 94%; MS(mass/charge): 519(MH+).++
973(S)-N2-[2-(N,N-Diethylaminomethyl)-1-methylbenzimidazole-5-yl]-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 7,21 min; purity: 97%; MS(mass/charge): 505(MH+).++
974N2-[2-(N,N-Diethylaminomethyl)-1-methylbenzimidazole-5-yl]-N4-(2,2-dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 7,51 min; purity: 97%; MS(mass/charge): 520(MH+). ++
975N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[2-(4-morpholino)-1H-benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 8,89 min; purity: 90%; MS(mass/charge): 475(MH+).++
976N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[2-(4-morpholino)-1H-benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 7,76 min; purity: 96%; MS(mass/charge): 505(MH+).++
977N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[2-(4-morpholino)-1H-benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 8,05 min; purity: 926%; MS(mass/charge): 506(MH+).++
978N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[2-(4-morpholino)-1H-benzimida the evil-5-yl]-2,4-pyrimidinediamine LC/MS: retention time: 8,03 min; purity: 92%; MS(mass/charge): 470(MH+).+
979N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[1-methyl-2-(4-methyl-1-piperazine derivatives)-1H-benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 8,12 min; purity: 98%; MS(mass/charge): 502(MH+).
980N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-[1-methyl-2-(4-methyl-1-piperazine derivatives)-1H-benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 7,34 min; purity: 96%; MS(mass/charge): 497(MH+).
981N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[1-methyl-2-(4-methyl-1-piperazine derivatives)-1H-benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 6,99 min; purity: 97%; MS(mass/charge): 532(MH+).
982(S)-5-fluoro-N2-[1-methyl-2-(4-methyl-1-piperazine derivatives)-1H-benzimidazole-5-yl]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: retention time: 6,62 min; purity: 97%; MS(mass/charge): 518(MH+).
983N4-(2,2-Dimethyl-3-oxo-4H-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-[1-methyl-2-(4-methyl-1-piperazine derivatives)-1H-benzimidazole-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 7,05 min; purity: 96%; MS(mass/charge): 533(MH+).
984N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine salt benzosulfimide acid1H NMR (DMSO-d6): d 11,22(1H, s), 9,79(1H, s), 9,62(1H, s), of 8.27(1H, d, J=3,9 Hz), 8,08(1H, d, J=4.5 Hz), 7.68 per-of 7.64(3H, m), 7,47(1H, d, J=8.7 Hz), 7,42-7,31(5H, m), 7,22(1H, t, J=8.1 Hz), 6,63(1H, DD, J=8,1 Hz, J=2.4 Hz), 4,47(2H, c), is 2.74 (3H, d, J=4.5 Hz), of 1.52 (6H, c) ; purity: 100%; MS (mass/charge): 468 (MH+).++/td> +
985N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR (DMSO-d6): d 11,23(1H, s), to 9.91(1H, s)to 9.70(1H, s), 8,29(1H, d, J=3,9 Hz), of 8.06(1H, m), 7,65-to 7.61(1H, m), 7,55(1H, d, J=8.1 Hz), of 7.48(1H, d, J=8.1 Hz), 7,33-to 7.18(5H, m), of 6.66(1H, d, J=7,5 Hz), 4,48(2H, s)of 2.75(3H, d, J=3.6 Hz), of 2.38 (3H, c), of 1.53 (6H, c) ; purity: 100%; MS (mass/charge): 468 (MH+).+++
986N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine cleaners containing hydrochloride salt1H NMR (DMSO-d6): d 11,18(1H, s), 9,54(2H, users), compared to 8.26(1H, s), with 8.05(1H, users), 7,70-7,66(1H, m), 7,47(1H, d, J=8,4 Hz), 7,40(1H, s), 7,34(1H, d, J=9 Hz), 7,20(1H, t, J=7.9 Hz), is 6.61(1H, d, J=7.5 Hz), 4,47(2H, s)of 2.75(3H, d, J=3.3 Hz), of 1.53 (6H, c) ; purity: 100%; MS (mass/charge): 468 (MH+).++
987N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimido the diamine bis-cleaners containing hydrochloride salt 1H NMR (DMSO-d6): d 11,18(1H, s), 9,50(2H, users), to 8.25(1H, d, J=3.3 Hz), of 8.06(1H, m), 7,74-to 7.67(1H, m), 7,47(1H, d, J=8,4 Hz), 7,41(1H, s), 7,37(1H, d, J=8.1 Hz), 7,20(1H, t, J=7.9 Hz), 6,59(1H, d, J=8.1 Hz), 4,47(2H, s), 2,74((3H, d, J=3.6 Hz), of 1.53 (6H, c); purity: 100%; MS (mass/charge): 468 (MH+).++
988N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine salt of nitric acid1H NMR (DMSO-d6): d 11,19(1H, s), 9,58(1H, users), 9,52(1H, s), of 8.25(1H, d, J=3.6 Hz), of 8.06(1H, m), 7,70-7,66(1H, m), 7,47(1H, d, J=8.7 Hz), 7,40(1H, s), 7,34(1H, d, J=8.1 Hz), 7,21(1H, t, J=8,1 Hz)that is 6.61(1H, d, J=7.5 Hz), 4,47(2H, c), is 2.74 (3H, d, J=3.6 Hz), of 1.53 (6H, c); purity: 100%; MS (mass/charge): 468 (MH+).++
989N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine salt of the bis-nitric acid1H NMR (DMSO-d6): d 11,21(1H, s), for 9.64(1H, users), 9,54(1H, s), compared to 8.26(1H, d, J=3.6 Hz), 8,07(1H, m), to 7.67(1H, d, J=8,4 Hz), 7,47(1H, d, J=8.7 Hz), 7,39(1H, s), 7,34(1H, d, J=7.8 Hz), 7,21(1H, t, J=8,2 Hz), 6,62(1H, d, J=8,4 Hz), 4,47 (2H, c), is 2.74 (3H, d, J=4.5 Hz), of 1.53 (6H, c); purity:95%; MS (mass/charge): 468 (MH+).++
990N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine salt methanesulfonic acid1H NMR (DMSO-d6): d 11,24(1H, s), 9,79(1H, users), 9,63(1H, s), of 8.27(1H, d, J=3,9 Hz), 8,07(1H, m), of 7.64(1H, d, J=8,4 Hz), of 7.48(1H, d, J=8,4 Hz), was 7.36(1H, s), 7,32(1H, d, J=7.5 Hz), 7,22(1H, t, J=7.9 Hz), only 6.64(1H, d, J=8.7 Hz), 4,47 (2H, c), is 2.74 (3H, d, J=4.5 Hz), 2,42 (3H, c), of 1.53 (6H, c); purity: 100%; MS (mass/charge): 468 (MH+).++
991N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine salt of(1S)-(+)-camphorsulfonic acid1H NMR (DMSO-d6): d at 11.25(1H, s), 9,72(1H, users), 9,59(1H, s), of 8.27(1H, d, J=3.6 Hz), 8,07(1H, m), the 7.65(1H, d, J=8,4 Hz), 7,47(1H, d, J=8.7 Hz), 7,37(1H, s), 7,33(1H, d, J=8.7 Hz), 7,21(1H, t, J=8.1 Hz), 6,62(1H, DD, J=8,1 Hz, J=2.4 Hz), 4,47 (2H, c), 2,96 (1H, d, J=14,7 Hz), 2,78 (1H, m), is 2.74 (3H, d, J=4.5 Hz), 2,47 (1H, d, J=14,7 Hz), 2,33 (2H, dt, J=18,9 Hz, J=3.75 Hz), 2,03 (1H, t, J=4.5 Hz), 1,98-1,90 (1H, m)to 1.98 (1H, d, J=17.7 and Hz)of 1.53 (6H, c)of 1.40 (1H, d, J=11.1 in Hz)of 1.33 (1H, d, J=10,2 Hz)to 1.14 (3H, c), is 0.84 (3H, c); purity: 100%; MS (mass/the poison): 468 (MH+). ++
992N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine salt of (+)-camphorsulfonic acid1H NMR (DMSO-d6): d 11,21(1H, s), 9,63(1H, users), 9,54(1H, s), compared to 8.26(1H, d, J=3.6 Hz), 8,07(1H, m), to 7.67(1H, d, J=8,4 Hz), 7,47(1H, d, J=8.7 Hz), 7,39(1H, s), 7,34(1H, d, J=8.1 Hz), 7,21(1H, t, J=8.1 Hz), is 6.61(1H, DD, J=8,1 Hz, J=1.8 Hz), 4,47 (2H, c), 2,95 (1H, d, J=14.4 Hz), 2,78 (1H, m),is 2.74 (3H, d, J=4.5 Hz), a 2.45 (1H, d, J=14.4 Hz), a 2.36 (1H, t, J=3.6 Hz), 2,30 (1H, t, J=4 Hz), 2,03 (1H, t, J=4.5 Hz), 2.00 in was 1.94 (1H, m), with 1.92 (1H, d, J=18 Hz), of 1.53 (6H, c)of 1.39 (1H, d, J=9.9 Hz), 1,33 (1H, d, J=10,2 Hz)to 1.14 (3H, c), is 0.84 (3H, c); purity: 100%; MS (mass/charge): 468 (MH+).++-
993N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(1-methylindol-6-yl)-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR (DMSO-d6): d 10,78(1H, s), 10,11(1H, users), of 9.89(1H, users), 8,29(1H, d, J=4,8 Hz), 8,01(1H, s), 7,95(1H, s), of 7.70(1H, d, J=8.7 Hz), 7,55(2H, d, J=8.1 Hz), 7,40(1H, d, J=8,4 Hz), 7,29-to 7.18(4H, m), to 6.95(1H, d, J=8.7 Hz), 3,91 (3H, c), of 2.38 (3H, c), for 1.49 (6H, c); purity: 100%; MS (mass/charge): 434 (MH+); Anal. Rasch. for C29H28FN7O5 C: C, 57,51; H, Of 4.66; N, 16,19; C, From 5.29, Found: C, 57,63; H And 4.65; N, 16,07; C, 4,95.+++
994N2-(3-Chloro-4-methoxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR (DMSO-d6): d of 10.73(1H, s), 9,65(1H, s), 9,41(1H, s), to 8.20(1H, d, J=4, 2 Hz), 7,71(1H, s), 7,54(2H, d, J=8.1 Hz), the 7.43(1H, s), 7,35(1H, DD, J=8,4 Hz, J=2.4 Hz), 7.23 percent-7,17(3H, m), 7,00(1H, d, J=8,4 Hz), 3,76(3H, s), of 2.38(3H, in), 2.25 (3H, c)a 1.50 (6H, c); purity: 100%; MS (mass/charge): 458 (MH+); Analysts. for C29H29ClFN5O6C: C, 55,28; H, With 4.64; N, 11.11 Is; C, 5,09 Found: C, 55,37; H, 4,74; N, 11.11 Is; C, 4,59.++++
995N2-(3-Chloro-4-hydroxy-5-were)-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,19(1H, d, J=1.5 Hz), 9,05(1H, s)8,64(1H, s), 8,10(1H, d, J=3,9 Hz), a 7.62(1H, d, J=2.7 Hz), was 7.36(1H, d, J=1,8 Hz), 7,31(1H, m), 7,27(1H, d, J=2.7 Hz), 6.87 in(1H, d, J=8,4 Hz), or 4.31(4H, s), 2,22(3H, s); LC/MS: purity: 96,98%; MS (mass/charge): 403 (MH+).+++
99 N2-(3-Chloro-4-hydroxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,16(1H, s), 9,27(1H, s)to 9.15(1H, s), 8,67(1H, s), 8,19(1H, d, J=3.6 Hz), to 7.64(2H, m), 7,42(1H, d, J=8,4 Hz), 7,29(1H, d, J=2.7 Hz), 2,22(3H, s)of 1.53(6H, s); LC/MS: purity: 97,69%; MS(mass/charge): 444(M+).++-
997N2-(3,5-Dimethyl-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,16(1H, s), 9,23(1H, s), 9,11(1H, s), 8,19(1H, d, J=3.6 Hz), 7,69(1H, d, J=8.1 Hz), 7,44(1H, d, J=8,4 Hz), 7,33(2H, s), 3,68(3H, s), of 2.23(6H, s)of 1.53(6H, s); LC/MS: purity: 99%; MS(mass/charge): 439(MH+).++-+
998N2-(3,5-Dimethyl-4-methoxyphenyl)-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 10,06(1H, s), 9,85(1H, s), of 8.25(1H, d, J=4,8 Hz), 7,33(1H, d, J=2.4 Hz), 7,24(2H, s), 7,20(1H, d, J=2.7 Hz), 6,91(1H, d, J=8,4 Hz), 4,32(4H, s), 3,71(3H, in), 2.25(6H, s); LC/MS: purity: 96,69%; MS(mass/charge): 397(MH+).++-
999N2-(3-Chloro-4-methoxy-5-were)-N4-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,88(2H, users), compared to 8.26(1H, d, J=4, 2 Hz), to 7.64(1H, s), 7,41(1H, s), 7,30-7,28(1H, m), 7,25-7,20(1H, m), 6,92(1H, d, J=10,2 Hz), 4,32(4H, s), with 3.79(3H, s)to 2.29(3H, s); LC/MS: purity: 94,81%; MS(mass/charge): 417(MH+).+++
1000N4-(3,4-Dihydro-2,2-dimethyl-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d to 9.15(1H, s), the remaining 9.08(1H, s), of 8.09(1H, d, J=3.6 Hz), of 8.04(1H, d, J=4.5 Hz), 7,45-7,42(2H, m), 7,17(1H, t, J=8,4 Hz), 7,01(1H, d, J=2.4 Hz), to 6.95(1H, d, J=8,4 Hz), of 6.65(1H, d, J=to 8.7 Hz), 6,53(1H, d, J=9.3 Hz), 5,88 (1H, c), of 4.44 (2H, c), of 3.07 (2H, c), is 2.74 (3H, d, J=4,2 Hz)of 1.34 (6H, c); purity: 96,6%; MS (mass/charge): 453 (M).+
1001N2-(3-Chloro-4-methoxy-5-were)-N4-(3,4-dihydro-2,2-dimethyl-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,59(1H, users), 8,17(1H, d, J=4, 2 Hz), the 7.65(1H, s), 7,46(1H, s), 6,94-6,86(2H, m), of 6.68(1H, d, J=8.7 Hz), of 3.77(3H, s), is 3.08(2H, s), and 2.27(3H, s)of 1.34(6H, s); purity: 94,5; MS(mass/charge): 444(M).+
1002N4-(3,4-Dihydro-2,2-dimethyl-4H-benzo[1,4]oxazin-6-yl)-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,06(2H, s), of 8.09(1H, d, J=3.6 Hz), 7,03(1H, DD, J=6,9 Hz, J=1.8 Hz), to 6.95(1H, DD, J=8,1 Hz, J=2.7 Hz), 6,63(1H, d, J=8.7 Hz), 6,11(1H, s), of 5.82(1H, s), 3,71(6H, s), of 3.07(2H, ), of 1.34(6H, s); purity 95,9%; MS((mass/charge): 426 (M).+
1003N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3-isopropylphenyl)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,17(1H, s), 9,27(1H, s), 9,24(1H, s), 8,21(1H, d, J=3.6 Hz), to 7.67(1H, m), to 7.61(1H, d, J=9 Hz), 7,52(1H, s), 7,44(1H, d, J=8.7 Hz), 7,19(1H, t, J=7,65 Hz), 6,85(1H, d, J=7,8 Hz), 2,82(1H, m)of 1.53(6H, s), 1,25 (6H, d, J= 6.9 Hz); purity of 97.7%; MS (mass/charge): 423 (MH+).++
1004N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(2-were)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,23(1H, s), 10,12(1H, s), 9,39(1H, s), of 8.27(1H, d, J=4,8 Hz), 7,52(1H, d, J=6.9 Hz), the 7.43(1H, d, J=8.7 Hz), 7,34-7,16(4H, m), is 2.30(3H, s)of 1.50(6H, s); purity 97,9%; MS(mass/charge): 395 (MH+).+-
10052-Chloro-5-fluoro-N4-methyl-N4-(3-oxo-2,2,4-trimethyl-5-pyrid[1,4]oxazin-6-yl)-4-pyrimidinamine1H NMR (DMSO-d6): d 8,43(1H, d, J=5,1 Hz), EUR 7.57(1H, d, J=8,4 Hz), to 7.15(1H, DD, J=8,1 Hz, J=0.9 Hz)and 3.59(3H, s), 3,30(3H, s)of 1.55(6H, s); purity 97,2%; MS(mass/charge): 352 (MH+).+-
10062-Chloro-5-fluoro-N4-(3-oxo-2,2,4-trimethyl-5-pyrid[1,4]oxazin-6-yl)-4-pyrimidinamine1H NMR (DMSO-d6): d 10,35(1H, s), of 8.47(1H, d, J=3.3 Hz), a 7.62(1H, d, J=8.7 Hz), 7,58(1H, d, J=8,4 Hz), of 3.45(3H, s)of 1.55(6H, s); purity 96%; MS(mass/charge): 338 (MH+).--
1007N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,14(1H, s), 9,24(1H, s), 9,19(1H, s), 8,21(1H, d, J=3.3 Hz), 7,76(1H, d, J=8.7 Hz), 7,41(1H, d, J=8.7 Hz), 7,12(2H, in), 3.75(6H, s), of 3.69(3H, s), of 1.52(6H, s); purity 96%; MS(the mass/charge): 47(MH+) ++-+
1008N2-(3-Chloro-4-ethoxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 10,67(1H, s), 9,40(1H, s), 9,20(1H, s), 8,16(1H, d, J=3,9 Hz), 7,74(1H, d, J=3 Hz), was 7.45(1H, d, J=2.7 Hz), was 7.36(1H, DD, J=8.7 Hz, J=2.4 Hz), 7,25(1H, d, J=2.4 Hz), 6,98(1H, d, J=8.7 Hz), of 3.94(2H, square, J=7,2 Hz), 2,24 (3H, c)a 1.50 (6H, c)of 1.41 (3H, t, J=6.9 Hz); purity 97%; MS (mass/charge): 472 (MH+).++++
1009N2-(3-Chloro-4-methoxy-5-were)-5-fluoro-N4-(3-oxo-2,2,4-trimethyl-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,62(1H, s), 9,41(1H, s), of 8.27(1H, s), 7,80(1H, s), 7,73(1H, d, J=8.7 Hz), of 7.48(1H, d, J=8.7 Hz), the 7.43(1H, s), of 3.78(3H, d, J=2.4 Hz), of 2.92(3H, s)of 1.55(6H, d, J=2.4 Hz); purity 97%; MS(mass/charge): 473(MH+).++-
1010N2-(3-Chloro-4-ethoxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,18(1H, s), 9,41(1H, s), 9,38(1H, s)8,23(1H, q, j =3.6 Hz), 7,74(1H, d, J=2.7 Hz), to 7.61(1H, d, J=8,4 Hz), 7,46(1H, d, J=8.1 Hz), 7,41(1H, d, J=2.1 Hz), 3,95(2H, square, J=7,2 Hz), and 2.27(3H, s)of 1.53(6H, s)of 1.42(3H, t, J=6.9 Hz); purity 99%; MS (mass/charge): 473 (MH+).+-
1011N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d a 10.74(1H, s), of 9.56(1H, s), 9,49(1H, s), 8,21-8,19(2H, m), 7,89(2H, d, J=9 Hz), to 7.84(2H, d, J=9 Hz), 7,37(1H, d, J=0.6 Hz), 7,33(1H, DD, J=8,1 Hz, J=2.4 Hz), 7,26(1H, d, J=2.7 Hz), 7,02(1H, d, J=8.7 Hz), of 1.53(6H, c); purity 96%; MS (mass/charge): 447 (MH+).++-+
10125-fluoro-N2-[3-(oxazol-2-yl)phenyl]-N4-[3-oxo-2,2,4-trimethyl-5-pyrid[1,4]oxazin-6-yl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,76(1H, s), 9,74(1H, s), to 8.41(1H, s), 8,32(1H, d, J=3.6 Hz), of 8.25(1H, s), 7,89-7,83(2H, m), of 7.64(1H, d, J=7.8 Hz), of 7.48(1H, d, J=7.8 Hz), 7,44(1H, s), of 7.36(1H, d, J=7,2 Hz), of 3.42(3H, s), and 1.54(6H, s); purity 96%.++-
10135-fluoro-N2-[4-(oxazol-2-yl)phenyl]-N4-[3-oxo-2,2,4-trimethyl-5-pyrid[1,4]oxazin-6-yl]-2,4-pyrimidinium is n 1H NMR (DMSO-d6): d 9,76(1H, s), 9,73(1H, s), 8,31(1H, d, J=3.6 Hz), 8,21(1H, d, J=0.9 Hz), 7,92(2H, d, J=9.3 Hz), 7,88(2H, d, J=9.6 Hz), 7,76(1H, d, J=8,4 Hz), 7,54(1H, d, J=8,4 Hz), 7,38(1H, d, J=0.9 Hz), 3,44(3H, s)of 1.57(6H, c); purity 96%; MS (mass/charge): 462 (MH+).+-
1014N2-[3-Chloro-4-ethoxycarbonylmethoxy-5-were]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 10,69(1H, s), 9,43(1H, s), 9,27(1H, s), 8,17(1H, d, J=3.6 Hz), 7,76(1H, d, J=2.7 Hz), 7,46(1H, d, J=2.4 Hz), was 7.36(1H, DD, J=9 Hz, J=2.7 Hz), 7,24(1H, d, J=2.4 Hz), of 6.99(1H, d, J=8,4 Hz), 4,58(2H, s), 4,28(2H, q, J=7,2 Hz), and 2.27 (3H, c)a 1.50 (6H, c)of 1.33 (3H, t, J=6.9 Hz); purity is 95.6%; MS (mass/charge): 530 (MH+).+++
10155-fluoro-N2-[3-(N-methylamino)carbonintensity]-N4-[3-oxo-2,2,4-trimethyl-5-pyrid[1,4]oxazin-6-yl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,58(1H, s), 9,42(1H, s), of 8.25(1H, d, J=3.3 Hz), of 8.06(1H, users), 7,88(1H, d, J=8,4 Hz), 7,49(2H, m), of 7.36(1H, d, J=7.5 Hz), 7,20(1H, t, J=8.1 Hz), 6,56(1H, DD, J=8,4 Hz, J=2,4 Hz), to 4.46(2H, s), 3,44(3H, s), is 2.74 (3H, d, J=4,8 Hz)of 1.55 (6H, c); purity 97,2%; MS (mass/charge): 482 (MH+).++/td> -
1016N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 10,67(1H, s), at 9.53(1H, s), 9,38(1H, s), of 8.47(1H, s), to 8.20(1H, d, J=3.6 Hz), of 8.04(1H, s), 7,78(1H, m), 7,58(1H, s), 7,41(1H, DD, J=8.7 Hz, J=2.4 Hz), 7,35(2H, d, J=4,8 Hz), 7,29(1H, d, J=2.4 Hz), 6.89 in(1H, d, J=8.7 Hz), for 1.49 (6H, c); purity 96%; MS (mass/charge): 447 (MH+).++-+
10175-fluoro-N2-[3-(oxazol-5-yl)phenyl]-N4-[3-oxo-2,2,4-trimethyl-5-pyrid[1,4]oxazin-6-yl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,65(1H, s)to 9.57(1H, s), of 8.47(1H, s), 8,29(1H, d, J=3.6 Hz), to 8.12(1H, s), 8,84(1H, d, J=8.1 Hz), 7,74(1H, m), a 7.62(1H, s), 7,43-to 7.32(3H, m), 3,42(3H, s), and 1.54(6H, s); purity 96,4%; MS(mass/charge): 462(MH+).++-
1018N2-[3-Chloro-4-cyclopentyloxy-5-were]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d is 10.68(1H, s), 9,41(1H, s), 9,20(1H, s), 8,16(1H, d, J=3.6 Hz), 7,73(1H, d, J=2.7 Hz), was 7.45(1H, d, J=2.4 Hz), was 7.36(1H, DD, J=9 Hz, J=2.7 Hz), 7,24(1H, d, J=2.4 Hz), 6,98(1H, d, J=8.7 Hz)and 4.65(1H, m), 2,23(H, c)a 2.0 a 1.6 (8H, m)of 1.50 (6H, c); purity of 98.3%; MS (mass/charge): 512 (MH+).++-
1019N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N4-methyl-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d of 10.72(1H, s), 9,65(1H, s)8,71(1H, s), of 8.27(1H, t, J=1.2 Hz), of 8.09(1H, DD, J=5.4 Hz, J=0.9 Hz), 7,82(1H, DD, J=8,1 Hz, J=0.9 Hz), 7,60(1H, d, J=8,4 Hz), of 7.48-the 7.43(2H, m), 7,05-6,97(2H, m), 6.87 in(1H, d, J=2.1 Hz), of 3.56 (3H, c)and 1.51 (6H, c); purity of 97.3%; MS (mass/charge): 461 (MH+).++-
1020N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d is 10.75(1H, s), of 9.56(1H, s), 9,49(1H, s), 8,43(1H, s), to 8.20(1H, d, J=3,9 Hz), 7,83(2H, d, J=8.7 Hz), to 7.59(2H, d, J=8.7 Hz), 7,53(1H, s), 7,33-7,28(2H, m), 7,02(1H, d, J=8,4 Hz), of 1.52(6H, s); purity of 97.4%; MS(mass/charge): 447 (MH+).++-
1021N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N4-methyl-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR (DMSO-6): d of 10.72(1H, C)9,72(1H, s), to 8.20(1H, d, J=0.9 Hz), 8,11(1H, d, J=5.7 Hz), 7,89(4H, s), 7,38(1H, d, J=0.9 Hz), 7,07-6,97(2H, m), 6.87 in(1H, d, J=2.7 Hz), of 3.54(3H, s), of 1.52(6H, s); purity to 97.1%; MS(mass/charge): 461(MH+).+++
1022N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N4-methyl-N2-[3-(N-methylamine)carbonintensity]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 10,70(1H, s), 9,38(1H, s), with 8.05(2H, d, J=5.4 Hz), 7,55(1H, m), 7,37(1H, d, J=8,4 Hz), 7,20(1H, t, J=7.8 Hz), 7,03(1H, d, J=8,4 Hz), 6,97(1H, DD, J=8,4 Hz, J=2.1 Hz), 6,85(1H, d, J=2.1 Hz), to 6.57(1H, DD, J=7.8 Hz, J=2.1 Hz), 4,49 (2H, c), 3,51 (3H, c), is 2.74 (3H, d, J=4.5 Hz), 1,50 (6H, c); purity 96.8 per cent; MS (mass/charge): 481 (MH+).++-
1023N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N4-methyl-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 10,71(1H, s), of 9.55(1H, s), and 8.50(1H, s)of 8.37(1H, s), 8,08(1H, d, J=5.7 Hz), to 7.68(1H, d, J=8.1 Hz), 7,66(1H, s), 7,43-7,34(2H, m), 7,05-6,97(2H, m), 6.87 in(1H, d, J=2.4 Hz), 3,55(3H, s)and 1.51(6H, s); purity is 95.6%; MS(mass/charge): 461 (MH+).++-
10241H NMR (DMSO-d6): d 9,71(1H, s), to 8.20(1H, d, J=0.9 Hz), 8,10(1H, d, J=6 Hz), of 7.90(4H, s), 7,38(1H, d, J=0.6 Hz), 7,27(1H, s), to 7.09(2H, s)and 3.59(3H, s)to 3.34(3H, s), of 1.52(6H, s); purity of 97.4%; MS(the mass/charge): 475(MH+).++
10255-fluoro-N4-methyl-N2-[3-(oxazol-2-yl)phenyl]-N4-(3-oxo-2,2,4-trimethylpent[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,65(1H, s), 8,72(1H, d, J=1,8 Hz), of 8.27(1H, d, J=0.6 Hz), 8,08(1H, d, J=6 Hz), 7,83-7,79(1H, m), 7,60(1H, d, J=7,2 Hz), 7,47(1H, d, J=7.8 Hz), the 7.43(1H, d, J=0.9 Hz), 7,28(1H with), 7,07(2H, s), 3,62(3H, s)to 3.35 (3H, c)and 1.51 (6H, c); purity of 97.3%; MS (mass/charge): 475 (MH+).++
10265-fluoro-N4-methyl-N2-[4-(oxazol-5-yl)phenyl]-N4-(2,2,4-trimethyl-3-oxo-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d a 9.60(1H, s), 8,44(1H, s), 8,07(1H, d, J=6 Hz), 7,88(2H, d, J=8,4 Hz), the 7.65(2H, d, J=8.7 Hz), EUR 7.57(1H, s), 7,27(1H, s), was 7.08(2H, s)to 3.58(3H, s)to 3.34(3H, s), of 1.52(6H, s); purity 98,61%; MS(mass/charge): 475(MH+).+-
1027N2-(3-Chloro-4-cyclopentyloxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,18(1H, s), 9,38(1H, s), a 9.35(1H, s), by 8.22(1H, d, J=3.6 Hz), 7,74(1H, d, J=2.4 Hz), to 7.61(1H, d, J=8.7 Hz), 7,46(1H, d, J=8,4 Hz), 7,41(1H, d, J=2.7 Hz), of 4.67(1H, m), and 2.26(3H with), 2,00-to 1.60(8H, m)of 1.53(6H, s); purity 94,95%; MS (mass/charge): 513 (MH+).+-
1028N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,18(1H, s), a 9.60(1H, s), 9,37(1H, s), scored 8.38(1H, s), of 8.27(2H, m), to 7.93(1H, d, J=8,4 Hz), 7,71(1H, d, J=8.7 Hz), 7,60(1H, d, J=8.1 Hz), 7,44-7,34(3H, m)of 1.53(6H, s); purity 95%; MS(mass/charge): 448(MH+).++-
1029N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-4-yl)phenyl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,17(1H, s), to 9.45(1H, s), 9,31(1H, s), 8,54(2H, DD, J=9.9 Hz, J=0.9 Hz), 8,24(1H, d, J=3.6 Hz), 8,10(1H, s), 7,78-7,72(2H, m), 7,42-7,29(3H, m), of 1.52(6H, s); purity 96,4%; MS(mass/charge): 448(MH+).++ -
10305-fluoro-N4-methyl-N2-[3-(oxazol-4-yl)phenyl]-N4-(3-oxo-2,2,4-trimethylpent[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d for 9.47(1H, s), 8,59(1H, s), 8,51(1H, s), to 8.41(1H, s), with 8.05(1H, d, J=5.4 Hz), 7,66(1H, d, J=7.5 Hz), 7,41-to 7.32(2H, m), 7,27(1H, s), 7,07(2H, s), of 3.60(3H, s)to 3.35(3H, s)and 1.51(6H, s); purity of 97.4%; MS(mass/charge): 475(MH+).++
1031N2-(3,5-Dimethyl-4-methoxyphenyl)-5-fluoro-N4-methyl-N4-(3-oxo-2,2,4-trimethylpent[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,11(1H, s), 8,00(1H, J=5.7 Hz), 7,42(2H, s), 7,24(1H, s), 7,05(2H, s), 3,68(3H, s), 3,55(3H, s)to 3.33(3H, in), 2.25(6H, s)and 1.51(6H, s); purity 97,84%; MS(mass/charge): 466(M).+-
1032N2-(3-Chloro-4-cyclopentyloxy-5-were)-5-fluoro-N4-methyl-N4-(3-oxo-2,2,4-trimethylpent[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,49(1H, s), 8,07(1H, DD, J=6 Hz, J=1.5 Hz), 7,81(1H, d, J=2.7 Hz), 7,47(1H, d, J=2.4 Hz), 7,27(1H, s), 7,07(2H, s), 4,69(1H, m), 3,61(3H, s)to 3.33(3H, s)to 2.29(3H, s), 2,0 to 1.6(8H, m)and 1.51(6H, s); purity 96,15%; MS (mass/charge): 540(M). --
1033N2-(3,5-Dimethyl-4-methoxyphenyl)-5-fluoro-N4-(3-oxo-2,2,4-trimethylpent[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,49(1H, d, J=0.9 Hz), to 9.15(1H, s), 8,21(1H, d, J=3.6 Hz), 7,81(1H, d, J=8.7 Hz), was 7.45(1H, d, J=8,4 Hz), 7,35(2H, s), of 3.69(3H, s), 3.43 points(3H, s), of 2.23(6H, s), and 1.54(6H, s); purity 98,82%; MS(mass/charge): 453(M).+++
1034N2-(3-Chloro-4-cyclopentyloxy-5-were)-5-fluoro-N4-(3-oxo-2,2,4-trimethylpent[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,63(1H, s), 9,40(1H, s), compared to 8.26(1H, d, J=3.6 Hz), 7,78(1H, d, J=2.4 Hz), 7,72(1H, d, J=8,4 Hz), of 7.48(1H, d, J=8,4 Hz), 7,41(1H, d, J=2.4 Hz), and 4.68(1H, m)to 3.41(3H, s), and 2.26(3H with), 1,95-to 1.60(8H, m), and 1.54(6H, s); purity 96%; MS (mass/charge): 527(MH+).+-
1035N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,23(1H, s)to 9.70(1H, s), at 9.53(1H, s), of 8.27(1H, d, J=3.6 Hz), to 8.20(1H, d, J=0.9 Hz), of 7.90(2H, d, J=9.3 Hz), 8,86(2H, d, J=9.5 to the TS) at 7.55(1H, d, J=8,4 Hz), 7,51(1H, d, J=8,4 Hz), 7,37(1H, J=0.9 Hz), and 1.56(6H, c); purity 96%; MS (mass/charge): 448 (MH+).-
1036N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-4-yl)phenyl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 10,65(1H, s), 9,41(1H, d, J=1.2 Hz), to 9.32(1H, s), and 8.50(1H, d, J=0.6 Hz), of 8.47(1H, s), 8,17(1H, d, J=3,9 Hz), 8,08(1H, s), 7,78(1H, d, J=8.7 Hz), the 7.43(1H, DD, J=8.7 Hz, J=2,4 Hz), 7,39-7,27(3H, m), to 6.88(1H, d, J=8.7 Hz), for 1.49 (6H, c); purity 98.9 per cent; MS (mass/charge): 447(MH+).+++
1037N2-[3-Chloro-5-methyl-4-(N-methylamino)carbonintensity]-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,19(1H, s), 9,43(2H, s), 8,24(1H, d, J=7.8 Hz), 8,18(1H, d, J=4.5 Hz), 7,78(1H, d, J=2.4 Hz), 7,60(1H, d, J=8,4 Hz), 7,47(1H, d, J=8,4 Hz), the 7.43(1H, d, J=2.4 Hz), 4,32(2H, ), and 2.79(3H, d, J=4,8 Hz)to 2.29(3H, c), of 1.53 (6H, c); purity of 97.6%; MS (mass/charge): 516(MH+).+-
1038N2-(3,5-Dimethyl-4-ethoxycarbonylmethylene)-N4-(2,2-dimethyl-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine 1H NMR (DMSO-d6): d 11,18(1H, s), 9,26(1H, s), 9,16(1H, s), 8,19(1H, d, J=3.3 Hz), to 7.68(1H, d, J=8,4 Hz), 7,46(1H, d, J=8,4 Hz), 7,33(2H, s), of 4.49(2H, s), 4,28(2H, square, J=7,2 Hz), of 2.23(6H, s), 1,52(6H, s)of 1.33(3H, t, J=7.2 Hz); purity 97,9%; MS (mass/charge): 511(MH+).+-
1039N2-(3-Chloro-4-isopropoxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d of 10.72(1H, s)9,68(1H, s), 9,44(1H, s), to 8.20(1H, d, J=3.6 Hz), of 7.70(1H, d, J=2.1 Hz), 7,42(1H, d, J=2.4 Hz), 7,35(1H, DD, J=8.7 Hz, J=2.4 Hz), 7,24(1H, d, J=2.4 Hz), 6,98(1H, d, J=8,4 Hz), 4,36(1H, Quint, J=6.0 Hz), of 2.23 (3H, c)a 1.50 (6H, c)of 1.32 (6H, d, J=6.3 Hz); purity 96.9 percent; MS (mass/charge): 486(MH+).++
1040N2-(3-Chloro-4-isopropoxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,17(1H, s), 9,37(1H, s), a 9.35(1H, s), by 8.22(1H, d, J=3.0 Hz), 7,74(1H, d, J=2.7 Hz), to 7.61(1H, d, J=8.7 Hz), was 7.45(1H, d, J=8.7 Hz), 7,41(1H, d, J=2.7 Hz), 4,36(1H, Quint, J=6.0 Hz in ), 2.25(3H, s), of 1.52(6H, s)of 1.33 (6H, d, J=6.3 Hz); purity of 97.3%; MS (mass/charge): 487(MH+).-+
1041N2-[3,5-Dimethyl-4-(N-methylamino)carbonintensity]-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,18(1H, s), 9.28 are(1H, s), 9,18(1H, s), 8,19(2H, d, J=3.6 Hz), to 7.68(1H, d, J=8,4 Hz), was 7.45(1H, d, J=8.7 Hz), 7,34(2H, s), 4,22(2H, s), and 2.79(3H, d, J=4.5 Hz), of 2.23(6H, s), 1,52(6H, s); purity 98%; MS(mass/charge): 496(MH+).+++
1042N2-(3-Chloro-4-ethoxycarbonylmethoxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,19(1H, s), 9,42(2H, s), 8,23(1H, d, J=3.6 Hz), 7,76(1H, d, J=2.4 Hz), 7,60(1H, d, J=8,4 Hz), 7,47(1H, d, J=8,4 Hz), 7,42(1H, d, J=2.1 Hz), 4,60(2H, s), 4,27(2H, square, J=7,2 Hz), to 2.29(3H, s), of 1.52(6H, s)of 1.33(3H, t, J=7.2 Hz); purity 98.4 per cent; MS (mass/charge): 531(MH+).--
1043N2-[3-Chloro-4-[N-(2,3-dihydroxypropyl)amino]carbonyloxy-5-were]-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,17(1H, s), 9,42(1H, s), 9,40(1H, s)8,23(1H, d, J=3.6 Hz), 7,98(1H, t, J=5.7 Hz), 7,78(1H, d, J=2.7 Hz), to 7.61(1H, d J=8.7 Hz), 7,47(1H, d, J=8,4 Hz), 7,34(1H, d, J=1,8 Hz), 4,94(1H, users), of 4.67(1H, user. c)4,36 (2H, c)to 3.67 (1H, t, J=6.3 Hz), 3,26-3,17 (1H, m), 2,3 (3H, c), of 1.53 (6H, c); purity of 97.3%; MS (mass/charge): 576(MH+).++-
1044N2-[3,5-Dimethyl-4-(N-cyclopentylamine)carbonintensity]-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,18(1H, s), 9,27(1H, s), 9,17(1H, s), 8,19(1H, d, J=3.6 Hz), 8,03(1H, d, J=7.8 Hz), to 7.67(1H, d, J=8.7 Hz), was 7.45(1H, d, J=8.7 Hz), 7,34(2H, s)to 4.23(1H, m), is 4.21(2H, s), 2.23 to(6H, s), at 1.91(2H, m)of 1.76(2H, m)to 1.60 (4H, m), of 1.52 (6H, c); purity 98%; MS (mass/charge): 550 (MH+).---
1045N4-(2,2-Debtor-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine cleaners containing hydrochloride salt1H NMR (DMSO-d6): d of 12.12(1H, s), for 9.95(1H, s), 9,58(1H, s), compared to 8.26(1H, d, J=3.6 Hz), of 8.06(1H, d, J=4, 2 Hz), the 7.65(1H, d, J=2.1 Hz), to 7.61(1H, d, J=2.4 Hz), 7,41(1H, s), 7,35(1H, d, J=8.7 Hz), 7,30(1H, d, J=9.0 Hz), 7,21(1H, t, J=7.8 Hz), is 6.61 (1H, d, J=8.1 Hz), 4,43 (2H, c), by 2.73 (3H, d, J=4.5 Hz); purity 100%; MS (mass/charge): 475 (MH+).++-
1046N4-(2,2-Debtor-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine salt methanesulfonic acid1H NMR (DMSO-d6): d a 12.05(1H, s), 9,81(1H, s), 9,38(1H, s), 8,24(1H, d, J=3.6 Hz), of 8.04(1H, d, J=4, 2 Hz), 7,66(1H, DD, J=10.5 Hz, J=1.5 Hz), 7,51(1H, d, J=1,8 Hz), the 7.43(1H, s), of 7.36-7.29 trend(2H, m), 7,19(1H, t, J=7.8 Hz), 6,59(1H, d, J=10.5 Hz), 4,42 (2H, c), by 2.73 (3H, d, J=4.5 Hz), 2,39 (3H, d, J=0.6 Hz); purity 100%; MS (mass/charge): 475 (MH+).++-
1047N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(indazol-6-yl)-2,4-pyrimidinediamine salt methanesulfonic acid1H NMR (DMSO-d6): d a 10.74(1H, s), 10,11(1H, s), 9,82(1H, s), compared to 8.26(1H, d, J=4.5 Hz), with 8.05(1H, s), 7,88(1H, s), 7,71(1H, d, J=8,4 Hz), was 7.45(1H, DD, J=9.0 Hz, J=2.7 Hz), 7,31(1H, DD, J=8.7 Hz, J=1.5 Hz), from 7.24(1H, d, J=2.4 Hz), 6,97 (1H, d, J=8.7 Hz), 2,43 (3H, c)to 1.48 (6H, c); purity 100%; MS (mass/charge): 420 (MH+).-+-
1048N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(indazol-6-yl)-2,4-pyrimidinediamine cleaners containing hydrochloride salt1H NMR (DMSO-d6): d of 10.73(1H, s), 9.28 are(1H, C)a 9.60(1H, s), 8,24(1H, d, J=4, 2 Hz), 8,02(2H, s), to 7.67(1H, d, J=8,4 Hz), 7,47(1H, d, J=8.7 Hz), of 7.36-7,33(2H, m), 6,98(1H, d, J=8.7 Hz), for 1.49(6H, s); purity of 99.3%; MS(mass/charge): 420(MH+).++-
1049N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(1-ethylindole-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,21(1H, s), of 9.56(1H, s), 9,40(1H, s), 8,29(1H, d, J=3.6 Hz), 8,11(1H, s), of 7.96(1H, s), 7,71(1H, d, J=7,2 Hz), to 7.64(1H, d, J=9.0 Hz), 7,46(1H, d, J=8,4 Hz), was 7.36(1H, DD, J=to 8.7 Hz, J=1.5 Hz), 4,25(2H, square, J=7,2 Hz), of 1.53 (6H, c)of 1.41 (3H, t, J=7.2 Hz); purity 100%; MS (mass/charge): 449 (MH+).++-
1050N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(1-isopropylindole-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,22(1H, s), of 9.56(1H, s), 9,41(1H, s), 8,29(1H, d, J=3.3 Hz), 8,15(1H, s), of 7.96(1H, s), of 7.70(1H, d, J=8,4 Hz), 7,63(1H, d, J=8,4 Hz), 7,46(1H, d, J=8.7 Hz), 7,35(1H, DD, J=to 8.7 Hz, J=1.2 Hz), 4,63(1H, Quint, J=6.6 Hz), of 1.53 (6H, c), for 1.49 (6H, d, J=6.3 Hz); purity 97,67%; MS (mass/charge): 463 (MH+).++-
10512-Chloro-N4-(,4-dihydro-2,2-dimethyl-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-4-pyrimidinamine 1H NMR (DMSO-d6): d 9,84(1H, s), 8,35(1H, d, J=3.3 Hz), to 7.09(1H, d, J=8.1 Hz), 7,06(1H, d, J=8.1 Hz), 6,79(1H, s), 3,23(2H, s)of 1.36(6H, s); purity 96,73%; MS(mass/charge): 310(MH+).--
1052N4-(3,4-Dihydro-2,2-dimethyl-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(1-methylindol-6-yl)-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,50(1H, s), to 8.94(1H, s), 8,21(1H, d, J=3.6 Hz), 8,17(1H, s), to 7.93(1H, s), 7,63(1H, d, J=8.7 Hz), 7,35(1H, d, J=1.5 Hz), 7,30(1H, d, J=7.8 Hz), 7,01(1H, d, J=8,4 Hz), 6,72(1H with), to 3.92(3H, s), 3,24(2H, d, J=2.4 Hz), of 1.37 (6H, c); purity 98,07%; MS (mass/charge): 421(M2H+).+++
1053N4-(3,4-Dihydro-2,2-dimethyl-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,29(1H, s), 8,83(1H, s), 8,15(1H, d, J=3.6 Hz), 8,03(1H, m), 7,47(1H, t, J=2.1 Hz), 7,40(1H, d, J=7.5 Hz), 7,34(1H, d, J=6.9 Hz), 7,20(1H, t, J=8,4 Hz), 7,02(1H, d, J=8,1 Hz), to 6.67(1H, s), 6,56(1H, DD, J=7.8 Hz, J=2.1 Hz), 4,46 (2H, c), 3,23 (2H, d, J=2.1 Hz), a 2.75 (3H, d, J=4.5 Hz), of 1.36 (6H, c); purity of 96.2%; MS (mass/charge): 454(MH+).++-
1054N2-[3-Chloro-4-(N-methylamino)carbonitril]-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,19(1H, s)to 9.70(1H, s)9,52(1H, s), of 8.28(1H, d, J=2.4 Hz), 8,21(1H, d, J=5,1 Hz), of 7.97(1H, s), a 7.62 EUR 7.57(2H, m)to 7.50(1H, d, J=9.0 Hz), 7,34(1H, d, J=8,4 Hz), of 2.81(3H, d, J=3.6 Hz), of 1.53(6H, s); 99.5%purity; MS (mass/charge): 472(MH+).++-
1055N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-(3,4-atlanticcity)-5-fluoro-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 11,12(1H, s), a 9.25(1H, s), 9,12(1H, s), 8,17(1H, d, J=3.3 Hz), to 7.64(1H, d, J=8,4 Hz), the 7.43(1H, d, J=8,4 Hz), 7,35(1H, d, J=2.4 Hz), 7,10(1H, DD, J=9.0 Hz, J=2.4 Hz), 6,76(1H, d, J=9.0 Hz), 4.26 deaths(4H, m)of 1.53(6H, c); purity 96.9 percent; MS (mass/charge): 439(MH+).++-
1056N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[1-methylindol-6-yl]-2,4-pyrimidinediamine cleaners containing hydrochloride salt1H NMR (DMSO-d6): d 11,23(1H, s), 9,88(1H, s), 9.28 are(1H, s), with 8.33(1H, d, J=3.6 Hz), 8,02(1H, s), 7,98(1H, s), 7,66(2H, t, J=8,4 Hz). was 7.45(1H, d, J=8,4 Hz), 7,31(1H, DD, J=8,4 Hz, J=1.5 Hz), 3,93(3H, s)of 1.53(6H, s); purity 100%; MS (mass/charge): 435(MH+). ++-
1057N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[1-methylindol-6-yl]-2,4-pyrimidinediamine salt p-toluensulfonate acid1H NMR (DMSO-d6): d 11,23(1H, s), 9,81(2H, s), 8,32(1H, d, J=3,9 Hz), 8,02(1H, s), 7,98(1H, s), to 7.67(2H, t, J=8.7 Hz), 7,55(2H, d, J=7.8 Hz), 7,44(1H, d, J=8,4 Hz), 7,31(1H, DD, J=8,4 Hz, J=0.9 Hz), 7,19(2H, d, J=8,4 Hz), of 3.94(3H, c), of 2.38 (3H, c), of 1.52 (6H, c); purity 98,8%; MS (mass/charge): 435(MH+).++-
1058N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[1-methylindol-6-yl]-2,4-pyrimidinediamine salt methanesulfonic acid1H NMR (DMSO-d6): d 11,22(1H, s), 9,76(1H, s), 9,72(1H, s), 8,31(1H, d, J=3.3 Hz), of 8.04(1H, s), of 7.97(1H, s), to 7.67(2H, d, J=8,4 Hz), was 7.45(1H, d, J=8.1 Hz), 3,32(1H, d, J=8,4 Hz), 3,93(3H, s), 2,41(3H, s)of 1.53(6H, s); purity 99%; MS (mass/charge): 435(MH+).++-
1059N2-(3,5-Dimethyl-4-methoxyphenyl)-5-fluoro-N4-(3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 2.13(s, 6H), to 3.58(s, 3H),to 4.62(s, 2H), 7,22(s, 2H), 7,33(d, J=9.0 Hz, 1H), EUR 7.57(d, J=8,4 Hz, 1H), 8,08(d, J=3.6 Hz, 1H), 9,01(s, 1H), 9.15, with(s, 1H), 11,13(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 163,82; LC/MS: retention time: 10,29 min; purity: 97,75%; MS(mass/charge): 411,18(MH+)+
1060N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(3-hydroxy-2-were)-2,4-pyrimidinediamine1H NMR(CDCl3): d 1,45(s, 6H), to 2.13(s, 3H), 6,78(m, 3H), of 6.90(d, J=7.5 Hz, 1H),? 7.04 baby mortality(t, J=8,1 Hz, 1H), 7,27(s, 1H), 7,74(d, J=5,1 Hz, 1H), to $ 7.91(s, 1H), which is 9.09(s, 1H), 10,86(s, 1H); 19F NMR(282 MHz, CDCl3): d - 162,90; LC/MS: retention time: 8,06 min; purity: 97,47%; MS (mass/charge): 410,21 (MH+).+
10615-fluoro-N2-(3-methoxy-2-were)-N4-(3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,99(s, 3H), 3,79(s, 3H), 4,60(s, 2H), is 6.54(d, J=7.8 Hz, 1H), 6,78(d, J=8,1 Hz, 1H), 6,98(DD, J=2.4 and 8.1 Hz, 1H), 7,12(t, J=8,4 Hz, 1H), 7,44(d, J=8.7 Hz, 1H), 8,03(d, J=3,9 Hz, 1H), 8,73(s, 1H), 9,23(s, 1H), 11,08 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 164,15; LC/MS: retention time: 8,97 min; purity: 99,74%; MS (mass/charge): 397,13 (MH+).+
1062N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(3-methoxy-2-were)-2,4-pyrimidinediamine1H NMR(CDCl3): d for 1.49(s, 6H), 2,12(s, 3H), of 3.95(s, 3H), of 6.71(DD, J=2.1 and 8.4 Hz, 1H), 6,79(d, J=8,4 Hz, 1H), 6.89 in(d, J=7.8 Hz, 1H), 6,98(d, J=8,4 Hz, 1H), 7,26(m, 3H), 7,66(d, J=4,2 Hz, 1H), 7,93(, 1H), 11,04(s, 1H); 19F NMR(282 MHz, CDCl3): d - 163,27; LC/MS: retention time: 9,36 min; purity: 99,94%; MS (mass/charge): 424,18 (MH+).+
10635-fluoro-N2-(3-hydroxy-2-were)-N4-(3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(CDCl3): d 2,02(s, 3H), 4,48(s, 2H), 6,72(m, 2H), PC 6.82(m, 1H), of 6.96(t, J=8,1 Hz, 1H), 7,25(m, 1H), 7,79(d, J=4,8 Hz, 1H); LC/MS: retention time: 7,10 min; purity: 77,55%; MS(mass/charge): 383,14(MH+).+
1064N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3-hydroxy-2-were)-2,4-pyrimidinediamine1H NMR(CDCl3): d of 1.41(s, 6H), 2,04(s, 3H), of 6.61(t, J=4.5 Hz, 1H), 6,94(m, 3H), 7,58(d, J=8.7 Hz, 1H), to 7.77(d, J=3,9 Hz, 1H); 19F NMR(282 MHz, CDCl3): d - 165,40; LC/MS: retention time: 7,83 min; purity: 99,01%; MS(mass is/charge): 411,19(MH+). +
1065N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3-methoxy-2-were)-2,4-pyrimidinediamine1H NMR(CDCl3): d of 1.57(s, 6H), are 2.19(s, 3H), 3,88(s, 3H), 6,79(DD, J=2.1 and 7.2 Hz, 1H), 7,05(d, J=8.7 Hz, 1H), 7,17(m, 2H), of 7.70(d, J=8.7 Hz, 1H), a 7.85(d, J=3.6 Hz, 1H); 19F NMR(282 MHz, CDCl3): d - 161,49; LC/MS: retention time: 10,92 min; purity 85,56%; MS (mass/charge): 425,17 (MH+).+
1066N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-methoxycarbonylmethylene-2-were]-2,4-pyrimidinediamine1H NMR(CDCl3): d for 1.49(s, 6H), and 2.26(s, 3H), of 3.80(s, 3H), 4,84(s, 2H), 6,69(DD, J=2.4 and 8.4 Hz, 1H), PC 6.82(d, J=8.7 Hz, 1H), 6,86(d, J=8,1 Hz, 1H), 6,98(d, J=8,1 Hz, 1H), 7,19(t, J=8,1 Hz, 1H), 7,26(, 1H), 7,46(s, 1H), 7,72(s, 1H), 7,79 (d, J= 4,8 Hz, 1H), 11,04 (c, 1H); 19F NMR (282 MHz, CDCl3): d - 162,94; LC/MS: retention time: of 9.21 min; purity: 99,68%; MS (mass/charge): 482,20 (MH+).+
1067N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[2-methyl-3-(N-METI is amino)carbonintensity]-2,4-pyrimidinediamine 1H NMR(CDCl3): d of 1.50(s, 6H), of 2.25(s, 3H), of 2.93(d, J=4,8 Hz, 3H), of 4.57(s, 2H), PC 6.82(m, 4H), 6,97(t, J=8,1 Hz, 1H), 7,19(m, 2H), 7,40(s, 1H), 7,54(s, 1H), 7,81(d, J=4,2 Hz, 1H); LC/MS: retention time: 8,08 min; purity: efficiency of 99.78%; MS(mass/charge): 481,21(MH+).+
10685-fluoro-N2-[2-methyl-3-(N-methylamino)carbonintensity]-N4-(3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 2.08(s, 3H), 2,66(d, J=4.5 Hz, 3H), of 4.46(s, 2H), 4,58(s, 2H), 6,65(DD, J=1.8 and 7.2 Hz, 1H),? 7.04 baby mortality(m, 2H), 7,15(d, J=8.7 Hz, 1H), 7,47(d, J=8.7 Hz, 1H), to 7.84(d, J=4,2 Hz, 1H), 8,01(d, J=3.6 Hz, 1H), 8,54(s, 1H), 8,96((c, 1H), 11,05 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 164,59; LC/MS: retention time: 7,60 min; purity: 76,95%; MS (mass/charge): 454,14 (MH+).+
1069N2-(3,5-Dimethyl-4-hydroxyphenyl)-5-fluoro-N4-(3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d is 2.09(s, 6H), to 4.62(s, 2H), 7,05(s, 2H), 7,28(d, J=8,4 Hz, 1H), 7,55(d, J=8,1 Hz, 1H), 7,89(user., 1H), 8,07(d, J=3.6 Hz, 1H), 9,03(s, 1H), 9,36(s, 1H), of 11.15(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 163,98; LC/MS: retention time: 7,9 min; purity: 77,84%; MS (mass/charge): 397,17 (MH+). +
1070N2-[3-(4-Ethoxycarbonylpyrimidine)phenyl]-5-fluoro-N4-(3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(CDCl3): d to 1.14(t, J=7.2 Hz, 3H), of 3.00(t, J=5.1 Hz, 4H), of 3.46(t, J=5.1 Hz, 4H), 4.00 points(sq, J=7.2 Hz, 2H), 4,47(s, 2H), 6,55(DD, J=1,8 and 8.4 Hz, 1H), 6.90 to(DD, J=1.2 and 7.8 Hz, 1H), 6,98(t, J=2.1 Hz, 1H),? 7.04 baby mortality(d, J=8.7 Hz, 1H), was 7.08 (t, J= 8,4 Hz, 1H), 7,73 (d, J= 8.7 Hz, 1H), 7,79 (d, J= 3,9 Hz, 1H); 19F NMR (282 MHz, CDCl3): d - 164,67; LC/MS: retention time: 11,64 min; purity: 96,15%; MS (mass/charge): 509,21 (MH+).+
1071N2-[3-(4-Acetylpiperidine)phenyl]-5-fluoro-N4-(3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(CDCl3): d a 2.01(s, 3H), to 3.02(t, J=5,1 Hz, 2H), is 3.08(t, J=5,1 Hz, 2H), 3,50(t, J=5,1 Hz, 2H), to 3.58(t, J=5.4 Hz, 2H), 4,50(s, 2H), 6,66(DD, J=2.4 and 8.4 Hz, 1H), 6.87 in(t, J=2.4 Hz, 1H), 6,92(DDD, J=0,9 and 2,1 and 7.8 Hz, 1H), 6,98(d, J= 8.7 Hz, 1H), 7,14 (t, J= 8,1 Hz, 1H), 7,60 (d, J= 8.7 Hz, 1H), 7,80 (d, J= 4,8 Hz, 1H); 19F NMR (282 MHz, CDCl3): d - 161,72; LC/MS: retention time: 9,23 min; purity: 73,82%; MS (mass/charge): 479,27 (MH+).+
1072 N2-[4-(4-Ethoxycarbonylpyrimidine)phenyl]-5-fluoro-N4-(3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.20(t, J=7.2 Hz, 3H), 2,99(t, J=5.1 Hz, 4H), 3,49(t, J=5.1 Hz, 4H), 4,05(sq, J=7.2 Hz, 2H), 4,63(s, 2H), 6,83(d, J=9,3 Hz, 2H), was 7.36(d, J=8,4 Hz, 1H), 7,47(d, J=9.0 Hz, 2H), 7,56(d, J=8,4 Hz, 1H), of 8.06(d, J=3,6 Hz, 11H), 9,01 (c, 1H), 9,14 (c, 1H), 11,13 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 164,19; LC/MS: retention time: 10,49 min; purity: 92,43%; MS (mass/charge): 509,27 (MH+).+
10735-fluoro-N2-(3-morpholinomethyl)-N4-(3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 2,98(t, J=5.1 Hz, 4H), of 3.69(t, J=5.1 Hz, 4H), to 4.62(s, 2H), 6,50(d, J=7.2 Hz, 1H),? 7.04 baby mortality(t, J=7.5 Hz, 1H), 7,17(d, J=7.2 Hz, 1H), 7,18(s, 1H), 7,33(d, J=8,4 Hz, 1H), 7,58(d, J=8,7 Hz, 1H), 8,11(d, J=3.6 Hz, 1H), which is 9.09(s, 1H), of 9.21 (c, 1H), 11,13 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 163,12; LC/MS: retention time: 9,27 min; purity: 94,96%; MS (mass/charge): 438,23 (MH+).+
10745-fluoro-N2-[3-(4-methylpiperazine)phenyl]-N4-(3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 2,85(s, 3H), 2,90(m, 2H), 3,23(m, 4H), to 3.67(m, 2H), 4.63 to(s, H), to 6.57(DD, J=2.1 and 8.4 Hz, 1H), was 7.08(t, J=8,1 Hz, 1H), 7,20(s, 1H), 7,28(m, 1H), 7,35(d, J=8,4 Hz, 1H), to 7.59(d, J=8,4 Hz, 1H), 8,11(d, J=3.3 Hz, 1H), 9, 13 (c, 1H), 9,26 (c, 1H), of 11.15 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 162,86; LC/MS: retention time: 6,70 min; purity: 85,78%; MS (mass/charge): 451 (MH+).+
1075N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,19(t, J=7.2 Hz, 3H), of 1.42(s, 6H), of 3.00(t, 4H), of 3.45(t, J=4.8 Hz, 4H), 4.04 the(sq, J=7.2 Hz, 2H), 6,51(d, J=9,3 Hz, 1H), 7,03(t, J=8,1 Hz, 1H), 7,18(s, 1H), 7,20(d, J=6,6 Hz, 1H), 7,34(t, J=8,4 Hz, 1H), to 7.59(d, J=8.7 Hz, 1H), 8,11 (d, J= 3.3 Hz, 1H), 9,14 (c, 1H), 9,25 (c, 1H), 11,09 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 163,08; LC/MS: retention time: 12,30 min; purity: 87,49%; MS (mass/charge): 537,33 (MH+).+
1076N2-[3-(4-Acetylpiperidine)phenyl]-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(CDCl3): d of 1.46(s, 6H), to 2.06(s, 3H), is 3.08(t, J=5,1 Hz, 2H), 3,13(t, J=5,1 Hz, 2H), 3,54(t, J=5,1 Hz, 2H), 3,65(t, J=5,1 Hz, 2H), to 6.67(DD, J=2.4 and 8.4 Hz, 1H), 6,94(t, J=2.1 Hz, 1H), 7,01(DDD, J of 0.9, 1.8 and 7.8 Hz, 1H), 7,05(d, J= 8.7 Hz, 1H), 7,18 (t, J= 8,1 Hz, 1H), 7,73 (d, J= 8.7 Hz, 1H), to 7.84 (d, J= 4.5 Hz, 1H); 19F NMR (282 MHz, CDCl3): d - 162,20; LC/MS: retention time: 9,92 min; purity: 92,80%; MS (mass/charge): 507,31 (MH+).+
1077N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.20(t, J=7.2 Hz, 3H), USD 1.43(s, 6H), 3,03(t, 4H), 3,50(t, 4H), 4,05(sq, J=7.2 Hz, 2H), to 6.88(d, J=9,3 Hz, 2H), 7,38(d, J=8,4 Hz, 1H), 7,45(d, J=9.9 Hz, 2H), 7,51(d, J=8.7 Hz, 1H), of 8.09(d, J=3,9 Hz, 1H), 9,24(s, 1H), 9,44(c, 1H), 11,12 (c, 1H); LC/MS: retention time: 10,90 min; purity: 91,64%; MS (mass/charge): 537,30 (MH+).+
1078N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.42(s, 6H), of 3.00(t, J=4.8 Hz, 4H), of 3.69(t, J=4.8 Hz, 4H), 6,51(DD, J=7.5 Hz, 1H),? 7.04 baby mortality(t, J=7.8 Hz, 1H), 7,16(s, 1H), 7,17(d, J=8,4 Hz, 1H), 7,34(d, J=8,4 Hz, 1H), to 7.59(d, J=8,4 Hz, 1H), 8,12(d, J=3.6 Hz, 1H), 9,17(c, 1H), 9,31 (c, 1H), 11,09 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 162,98; LC/MS: retention time: 10,81 min; purity: 98,57%; MS (mass/charge): 466,27 (MH+).+
1079N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[2-methyl-3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.39(s, 6H), of 2.08(s, 3H), 2,65(d, J=4,8 Hz, 3H), of 4.45(s, 2H), only 6.64(DD, J=2.7 and 6.6 Hz, 1H),? 7.04 baby mortality(m, 2H), 7,15(d, J=8,4 Hz, 1H), of 7.48(d, J=8,4 Hz, 1H), to 7.84(d, J=3,9 Hz, 1H), 8,01(d, J=3.6 Hz, 1H), 8,56(s, 1H), 8,98(c, 1H), br11.01 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 164,69; LC/MS: retention time: 8,73 min; purity: 96,88%; MS (mass/charge): 482,26 (MH+).+
1080N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(CDCl3): d of 1.42(s, 6H), 2,77(s, 3H), 3,20(m, 4H), 3,30(m, 4H), of 6.61(d, J=6,9 Hz, 1H), 6,92(t, J=2.4 Hz, 1H),? 7.04 baby mortality(d, J=8,4 Hz, 1H), 7,13(m, 2H), of 7.70(d, J=8.7 Hz, 1H), 7,81(d, J=4,2 Hz, 1H); 19F NMR(282 MHz, CDCl3): d - 162,81; LC/MS: retention time: 8,54 min; purity: 83,90%; MS (mass/charge): 479,38 (MH+).+
1081(S)-N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d ,45(d, J=6.6 Hz, 3H), of 3.77(s, 3H), 4,73(sq, J=6,6 Hz, 1H), 6,99(d, J=9.0 Hz, 1H), 7,38(d, J=8,4 Hz, 1H), of 7.48(m, 2H), 7,80(d, J=2.1 Hz, 1H), 8,11(d, J=3.6 Hz, 1H), of 9.21(s, 1H), 9,26(s, 1H), 11,09(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 163,36; LC/MS: retention time: 11,59 min; purity: 97,70%; MS (mass/charge): 431,16 (MH+).++
1082(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.45(d, J=6.9 Hz, 3H)and 3.59(s, 3H), of 3.65(s, 6H), 4.72 in(sq, J=6,6 Hz, 1H), 7,02(s, 2H), 7,32(d, J=8.7 Hz, 1H), 7,65(d, J=8,4 Hz, 1H), 8,11(d, J=3.3 Hz, 1H), 9,10(s, 1H), 9,17(, 1H), 11,07(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 162,83; LC/MS: retention time: 10,07 min; purity: 90,75%; MS (mass/charge): 457,22 (MH+).++
1083N2,N4-Bis(3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 4.46(s, 2H), to 4.52(s, 2H), 6,76(d, J=9,3 Hz, 1H), 6,86(d, J=8.7 Hz, 1H), 7,18(m, 2H), 7.23 percent(d, J=2.4 Hz, 1H), 7,33(DD, J=2.4 and 8.7 Hz, 1H), 8,00(d, J=3.6 Hz, 1H), to 8.94(s, 1H), 9,29(s, 1H), of 10.58(s, 1H), 10,63(c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 164,54; LC/MS: retention time: 7,32 min; purity: 85,68%; MS (mass/charge): 423,13 (MH+).+ ++
1084(S)-N2-(3, 5dimethylphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.44(d, J=6.9 Hz, 3H), 2,17(s, 6H), 4.72 in(sq, J=6,9 Hz, 1H), of 6.52(s, 1H), 7,22(s, 2H), 7,35(d, J=8.7 Hz, 1H), 7,89(d, J=8,4 Hz, 1H), 8,11(d, J=3.6 Hz, 1H), which is 9.09(s, 1H), 9,16(, 1H), 11,08(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 163,48; LC/MS: retention time: 12,47 min; purity: 96,01%; MS (mass/charge): 395,14 (MH+).-+
1085N2-[3-(4-Acetylpiperidine)phenyl]-N4-cyclobutyl-5-fluoro-2,4-pyrimidinediamine1H NMR(CDCl3): d is 1.82(m, 2H), 2,03(m, 2H), of 2.15(s, 3H), 2,46(m, 2H), 3,20(m, 4H), 3,63(t, J=5,1 Hz, 2H), 3,78(t, J=5,1 Hz, 2H), 4,58(m, J=8,1 Hz, 1H), 5,26(d, J=6,6 Hz, 1H), return of 6.58(DD, J=1.8 and 8.1 Hz, 1H), 7,01(DD, J=1.5 and 7.8 Hz, 1H), 7,19 (t, J= 8,1 Hz, 1H), 7,28 (user. 1H), 7,34 (t, J= 2.1 Hz, 1H), 7,74 (d, J= 3.3 Hz, 1H); 19F NMR (282 MHz, CDCl3): d - 168,12; LC/MS: retention time: 8,93 min; purity: 84,56%; MS (mass/charge): 385,77 (MH+).+-
1086N2-(5-tert-Butylphenol-3-yl)-5-fluoro-N4-(3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d of 1.29(s, 9H), with 4.64(s, 2H), 5,59(s, 1H), 7,10(d, 1H), 7,47(d, J=6,6 Hz, 1H), 8,24(d, 1H), 10,02(s, 1H), the 10.40(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 162,59; LC/MS: retention time: 10,51 min; purity: 78,44%; MS(mass/charge): 399,24(MH+).+-
1087N4-Cyclobutyl-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(CDCl3): d 1,78-to 1.87(m, 2H), 1,96-2,03(m, 2H), 2,32(s, 6H), 2,44 of $ 2.53(m, 2H), 4,56(m, J=7.8 Hz, 1H), 5,26(d, J=7.8 Hz, 1H), to 6.67(s, 1H), 7.23 percent(s, 2H), 7,34(user., NH, 1H), 7,72(d, J=2.7 Hz, 1H); 19F NMR(282 MHz, CDCl3): d - 168,35; LC/MS: retention time: 13,76 min; purity: 80,20%; MS (mass/charge): 287,35 (MH+).++-
1088N4-Cyclobutyl-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(CDCl3): d 1,71 is 1.86(m, 2H), 1.93 and e 2.06(m, 2H), 2,43 of $ 2.53(m, 2H), 3,81(s, 6H), 4,60(m, J=7.8 Hz, 1H), 5,31(d, 1H), 6,16(t, J=2.1 Hz, 1H), at 6.84(d, J=2.1 Hz, 2H), EUR 7.57(user., NH, 1H), 7,72(d, J=3.6 Hz, 1H); 19F NMR(282 MHz, CDCl3): d - 167,56; LC/MS: retention time: to 12.44 min; purity: 87,82%; MS (mass/charge): 319,32 (MH+).++-
1089 N4-Cyclobutyl-5-fluoro-N2-(3-methoxy-5-triptoreline)-2,4-pyrimidinediamine1H NMR(CDCl3): d 1,75-2,04(m, 4H), 2,43 of $ 2.53(m, 2H), 3,85(s, 3H), 4,58(m, J=7.8 Hz, 1H), 5,32(d, J=6,6 Hz, 1H), 6,76(s, 1H), 7,18(t, J=2.1 Hz, 1H), 7,52(user., NH, 1H), 7,76(s, 2H); 19F NMR(282 MHz, CDCl3): d - 167,20, -63,67; LC/MS: retention time: 13,22 min; purity: 82,74%; MS (mass/charge): 357,19 (MH+).++-
1090N4-(5-tert-Butyl-1H-pyrazole-3-yl)-5-fluoro-N2-(3-morpholinomethyl)-2,4-pyrimidinediamineLC/MS: retention time: 11,58 min; purity: 90,45%; MS(mass/charge): 412,33(MH+).++-
1091N2-[3-(4-Acetylpiperidine)phenyl]-N4-(5-tert-butyl-1H-pyrazole-3-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(CDCl3): d of 1.20(s, 9H), 2,04(s, 3H), 3,06(t, J=5.4 Hz, 2H), 3,11(t, J=5,1 Hz, 2H), 3,53(t, J=5,1 Hz, 2H), 3,63(t, J=5,1 Hz, 2H), 6,10(s, 1H), to 6.57(m, 1H), of 6.96(s, 1H), 7,13(m, 2H), 7,82(d, J=3,9 Hz, 1H); LC/MS: retention time: 8,84 min; purity: 90,18%; MS (mass/charge): 453,27 (MH+).++-
1092 (S)-N2-(5-tert-Butyl-1H-pyrazole-3-yl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-5-pyrid[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.30(s, 9H), 1,47(d, J=6.6 Hz, 3H), 4,74(sq, J=6.3 Hz, 1H), ceiling of 5.60(s, 1H), to 7.09(d, J=9.0 Hz, 1H), 7,49(d, J=8,4 Hz, 1H), 8,23(d, J=3,9 Hz, 1H), 10,02(s, 1H), accounted for 10.39(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 162,62; LC/MS: retention time: to 11.61 min; purity: 88,68%; MS (mass/charge): 413,17 (MH+).++-
1093N2-(3,5-Dimethyl-4-methoxyphenyl)-5-fluoro-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 2.16(s, 6H), 3,61(s, 4H), to 3.64(s, 3H), 6,98(d, J=11 Hz, 1H), 7,00(s, 1H), 7.23 percent(s, 1H), 7,35(t, J=8,1 Hz, 1H), of 7.75(d, J=6,6 Hz, 1H), 8,19(d, J=4.5 Hz, 1H), 8,29(s, 2H), to 9.57(s, 1H), of 9.89(s, 1H), was 10.82(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 162,53; LC/MS: retention time: 7,49 min; purity: 83,77%; MS (mass/charge): 422 (MH+).++-+
10945-fluoro-N2-(3-fluoro-4-methoxyphenyl)-N4-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 3,63(s, 4H), 3,79(s, 3H), of 6.96(d, J=9,3 Hz, 1H),? 7.04 baby mortality(t, J=9,3 Hz, 1H), 7,28(m, 1H), was 7.36(t, J=8,1 Hz, 1H), 7,63(DD, J=2,1, to 13.8 Hz, 1H), 7,68(d, J=9.6 Hz, 1H), 7,80(s, 1H), 8,18(d, J=4,2 Hz, 1H), of 8.27(s, 1H), of 9.56(s, 1H), 9,75 (c, 1H), 1072 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 162,96, -134,40; LC/MS: retention time: 6,99 min; purity: 81,44%; MS (mass/charge): 412 (MH+).+-
1095N2-(3, 5dimethylphenyl)-5-fluoro-N4-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 2.20(s, 6H), of 3.60(s, 4H), 6,92(s, 1H), 6,98(m, 1H), 7,22(s, 1H), 7,35(t, J=8,1 Hz, 1H), 7,73(d, J=7.8 Hz, 1H), 7,80(s, 1H), 8,21(d, J=4,2 Hz, 1H), compared to 8.26(s, 2H), 9,60(s, 1H), 9,86(s, 1H), 10,80(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 162,49; LC/MS: retention time: to $ 7.91 min; purity: 81,26%; MS (mass/charge): 392 (MH+).+-
1096N2-(3,5-Acid)-5-fluoro-N4-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 3,62(s, 4H), 3,66(s, 6H), 6,13(t, J=2.1 Hz, 1H), 6,92(d, J=2.1 Hz, 1H), 6,95(DD, J=1,5, and 8.4 Hz, 1H), 7,34(t, J=8,4 Hz, 1H), 7,71(d, J=8,1 Hz, 1H), to 7.93(s, 1H), to 8.20(d, J=3,9 Hz, 1H), compared to 8.26(s, 2H), being 9.61(s, 1H), 9,81(s, 1H), 10,86 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 162,22; LC/MS: retention time: 7,49 min; purity: 80,65%; MS (mass/charge): 424 (MH+).+--
1097 5-fluoro-N4-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-N2-(3-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 3.01(t, J=4.5 Hz, 4H), of 3.60(s, 4H), 3,70(t, J=4.5 Hz, 4H), 6,51(DD, J=2.1 a, and 8.4 Hz, 1H), 6.90 to(DD, J=1.5 and 7.8 Hz, 1H), 7,05(t, J=8,1 Hz, 1H), 7,29(m, 3H), of 7.64(d, J=7.8 Hz, 1H), 8,01(s, 1H), 8,12(d, J=3.6 Hz, 1H), 9,20(c, 1H), 9,48 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 163,75; LC/MS: retention time: 6,28 min; purity: 87,59%; MS (mass/charge): 449 (MH+).--
1098N2-[3-(4-Ethoxycarbonylpyrimidine)phenyl]-5-fluoro-N4-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.20(t, J=7.2 Hz, 3H), to 3.02(t, J=5.4 Hz, 4H), 3,47(t, J=5.4 Hz, 4H), of 3.60(s, 4H), 4,05(sq, J=7.2 Hz, 2H), 6,53(DD, J=1,5, and 8.4 Hz, 1H), make 6.90(d, J=8,1 Hz, 1H), 7,06(t, J=8,1 Hz, 1H), 7,30(m, 3H), 7,66(d, J=8.7 Hz, 1H), 7,99 (c, 1H), 8,12 (d, J= 3.6 Hz, 1H), 9,19 (c, 1H), 9,48 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 163,72; LC/MS: retention time: 9,11 min; purity: 94,51%; MS (mass/charge): 520,34 (MH+).--
10995-fluoro-N4-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 3,30(m, 4H), 3,62(s, 4H), at 6.84(d, J=9.0 Hz, 2H), ,91(d, J=8,1 Hz, 1H), 7,35(t, J=8,1 Hz, 1H), 7,49(d, J=8,4 Hz, 2H), 7,73(d, J=8,4 Hz, 1H), 7,80(s, 1H), of 8.09(d, J=3.3 Hz, 1H), of 8.27(s, 1H), 9,06(s, 1H), 9,44(s, 1H); 19F NMR (282 MHz, DMSO-d6): d - 163,72; LC/MS: retention time: 2,86 min; purity: 84,74%; MS (mass/charge): 462,37 (MH+).--
11005-fluoro-N4-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-N2-[4-(4-methoxycarbonylamino)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 3.00(t, J=5.1 Hz, 4H), 3,50(t, J=4.5 Hz, 4H), 3,61(s, 7H), at 6.84(d, J=9.0 Hz, 2H), 6,91(DD, J=1.5 and 7.5 Hz, 1H), 7,34(t, J=7.8 Hz, 1H), 7,52(d, J=8.7 Hz, 2H), 7,66(d, J=8,1 Hz, 1H), 7,94(s, 1H), 8,08(d, J=3.6 Hz, 1H), 9,11 (c, 1H), 9,44 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 164,62; LC/MS: retention time: 6,94 min; purity: 86,06%; MS (mass/charge): 506 (MH+).--
1101N4-(5-tert-Butyl-1H-pyrazole-3-yl)-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(CDCl3): d of 1.28(t, J=7.2 Hz, 3H), of 1.31(s, 9H), of 3.13(t, J=5.1 Hz, 4H), of 3.60(t, J=5.4 Hz, 4H), 4,15(sq, J=7.2 Hz, 2H), 6.35mm(s, 1H), is 6.61(m, 1H), 7,03(s, 1H), 7,18(m, 2H), 7,73(user., 1H), of 7.90(d, J=3.3 Hz, 1H), 8,20(user., 1H); 19F NMR(282 MHz, CDCl3): d - 166,45; LC/MS: retention time: to 12.52 min; purity: 86,92%; MS (mass/charge): 483,37 (MH+). +-
1102N2-[4-(4-Acetylpiperidine)phenyl]-N4-(5-tert-butyl-1H-pyrazole-3-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 8,02 min; purity: 94,49%; MS(mass/charge): 453,29(MH+).++-
1103N4-(5-tert-Butyl-1H-pyrazole-3-yl)-5-fluoro-N2-[4-(4-methoxycarbonylamino)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 10,38 min; purity: 97,48%; MS(mass/charge): 469,35(MH+).++-
1104N4-(5-tert-Butyl-1H-pyrazole-3-yl)-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.26(s, 9H), 2,61(m, 7H), to 3.00(m, 4H), 6,30(user., 1H), 6,86(d, J=8,4 Hz, 2H), of 7.48(d, J=9,3 Hz, 2H), of 7.97(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 165,34; LC/MS: retention time: 6,04 min; purity: 90,75%; MS(mass/charge): 425(MH+).++-
1105 N2-[4-(4-Acetylpiperidine)phenyl]-5-fluoro-N4-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 2,04(s, 3H), of 2.97(t, J=4,8 Hz, 2H), 3.04 from(t, J=4,8 Hz, 2H), only 3.57(m, 4H), 3,61(s, 4H), at 6.84(d, J=9.0 Hz, 2H), make 6.90(d, J=9,3 Hz, 1H), 7,33(t, J=7.8 Hz, 1H), 7,50(d, J=8.7 Hz, 2H,), of 7.69(d, J=8.7 Hz, 1H), 7,79(s, 1H), 8,08(d, J= 3.6 Hz, 1H), 9,04 (c, 1H), 9,40 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 164,70; LC/MS: retention time: 7,00 min; purity: 93%; MS (mass/charge): 490,32 (MH+).--
1106N2-[3-(4-Acetylpiperidine)phenyl]-5-fluoro-N4-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-2,4-pyrimidinediamineLC/MS: retention time: 7,31 min; purity: 84,11%; MS(mass/charge): 490,34(MH+).--
1107N4-Cyclobutyl-N2-[2-(etoxycarbonyl)indol-7-yl]-5-fluoro-2,4-pyrimidinediamine1H NMR(CDCl3): d of 1.42(t, J=7.2 Hz, 3H), 1,63-to 2.06(m, 4H), 2,27-of 2.36(m, 2H), to 4.41(sq, J=7.2 Hz, 2H), 5,17(d, J=6.0 Hz, 1H), 7,06(t, J=7.8 Hz, 1H), 7,14(d, 1H), 7,22(m, 2H), 7,28(user., 1H), 7,44(d, J=7.8 Hz, 1H), 7,76(d, J=3.6 Hz, 1H), is 10.68 of user. 1H); 19F NMR (282 MHz, CDCl3): d - 168,82; LC/MS: retention time: 10,65 min; purity: 82,48%; MS (mass/charge): 370,20 (MH+).+ +
1108N4-Cyclobutyl-5-fluoro-N2-(3-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(CDCl3): d 1,73-2,05(m, 4H), 2.40 a-2,50(m, 2H), 3,20(t, J=4.8 Hz, 4H), 3,88(t, J=4.8 Hz, 4H), 4,60(m, J=7.8 Hz, 1H), 5,14(d, J=6.3 Hz, 1H), to 6.57(DD, J=2,4, 8,1 Hz, 1H), 6,97(DD, J=1,8, 7.5 Hz, 1H), 7,06(user., NH, 1H), 7,19(t, J=8,1 Hz, 1H), 7,35 (t, J= 2.4 Hz, 1H), of 7.75 (d, J= 3.0 Hz, 1H); 19F NMR (282 MHz, CDCl3): d - 168,59; LC/MS: retention time: to 10.09 min; purity: 92,98%; MS (mass/charge): 344,32 (MH+).++-
1109N4-Cyclobutyl-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(CDCl3): d of 1.29(t, J=6.9 Hz, 3H), 1,71-2,02(m, 4H), 2,41 is 2.51(m, 2H), 3,18(t, J=5.1 Hz, 4H), to 3.64(t, J=5.1 Hz, 4H), 4,17(sq, J=6,9 Hz, 2H), 4,59(m, J=8,1 Hz, 1H), 5,16(d, J=7.8 Hz, 1H), return of 6.58(DD, J=2,4, 8,1 Hz, 1H), 6,97(DD, J=1,8, 8,1 Hz, 1H), 7,09 (user. NH, 1H), 7,18 (t, J= 8,1 Hz, 1H), 7,37 (t, J= 2.1 Hz, 1H), 7,74 (d, J= 2.7 Hz, 1H); 19F NMR (282 MHz, CDCl3): d - 168,46; LC/MS: retention time: of 10.05 min; purity: 89,70%; MS (mass/charge): 415,32 (MH+).+-
1110N4-Cyclobutyl-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidine the Ying 1H NMR(CDCl3): d 1,65-of 1.74(m, 2H), 1.85 to 1,95(m, 2H), 2,19 is 2.33(m, 2H), 2,71(s, 3H), 3.15 in(t, 4H), 3,32(t, J=4.8 Hz, 4H), 4,36(m, J=8,1 Hz, 1H), 6,80(d, J=9.0 Hz, 2H), was 7.36(d, J=9,3 Hz, 2H), 7,55(d, J=4,2 Hz, 1H); 19F NMR(282 MHz, CDCl3): ): d - 167,73; LC/MS: retention time: 6,03 min; purity: 90,91%; MS (mass/charge): 357,33 (MH+).+-
1111N4-Cyclobutyl-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(CDCl3): d is 1.31(t, 3H), 1,50-2,04(m, 4H), 2,41-of 2.50(m, 2H), is 3.08(t, J=4.8 Hz, 4H), to 3.64(t, J=5.1 Hz, 4H), 4,17(square, 2H), to 4.52(m, J=7.8 Hz, 1H), 5,18(d, J=6,6 Hz, 1H), make 6.90(d, J=9.0 Hz, 2H), 7,07(user., 1H), 7,45(d, J=9.0 Hz, 2H), of 7.70(d, J= 3.3 Hz, 1H); 19F NMR (282 MHz, CDCl3): d - 168,95; LC/MS: retention time: of 10.73 min; purity: 83,62%; MS (mass/charge): 415,34 (MH+).+-
1112N2-[3-(4-Acetylpiperidine)phenyl]-N4-(3-cyclopropyl-1H-pyrazole-5-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 9,04 min; purity: 87,21%; MS(mass/charge): 437,32(MH+).+++
1113 N4-(3-Cyclopropyl-1H-pyrazole-5-yl)-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(CDCl3): d 0,54-of 0.64(m, 2H), 0,76 is 0.86(m, 2H), 1,74(m, 1H), 2,42(s, 3H), was 2.76(user., 4H), 3,17(t, J=4.8 Hz, 4H), 5,90(user., 1H), PC 6.82(d, J=8.7 Hz, 2H), 7,29(d, J=8.7 Hz, 2H), 7,71(d, J=3.6 Hz, 1H); 19F NMR(282 MHz, CDCl3): d - 167,69; LC/MS: retention time: 5,97 min; purity: 76,80%; MS (mass/charge): 409,22 (MH+).++-
1114N4-(3-Cyclopropyl-1H-pyrazole-5-yl)-5-fluoro-N2-(3-morpholinomethyl)-2,4-pyrimidinediamineLC/MS: retention time: to 8.57 min; purity: 88,76%; MS(mass/charge): 396,24(MH+).++-
1115N4-(3-Cyclopropyl-1H-pyrazole-5-yl)-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 0.67(m, 2H), 0.88 to(m, 2H), 1,19(t, J=7,1 Hz, 3H), of 1.85(m, 1H), 3,06(m, 4H), of 3.48(m, 4H), 4,05(sq, J=7,1 Hz, 2H), of 6.52(d, J=8,1 Hz, 1H), 7,07(m, 1H), 7,20(m, 2H); LC/MS: retention time: 11,80 min; purity: 79,43%; MS(mass/charge): 467,30 (MH+).++
1116 N4-(3-Cyclopropyl-1H-pyrazole-5-yl)-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 0.62(m, 2H), 0,90(m, 2H), 1,20(t, J=7.2 Hz, 3H), of 1.84(m, J=3,9 Hz, 1H), is 3.08(user., 4H), 3,44(user., 4H), 4,05(sq, J=6,9 Hz, 2H), 6,12(user., 1H), 6,93(d, J=8.7 Hz, 2H), 7,40(d, J=8,4 Hz, 2H), 8,02(d, J=4,2 Hz, 1H), 9,37(user., 1H), 10,71 (user. 1H), 11,49 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 171,17; LC/MS: retention time: 9,23 min; purity: 94,89%; MS (mass/charge): 467,29 (MH+).++
11172-Chloro-5-fluoro-N4-(3,4-dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-4-pyrimidinamine1H NMR(DMSO-d6): d 3,40(t, J=4.5 Hz, 2H), 4,10(t, J=4.5 Hz, 2H), 6,92(d, J=8,4 Hz, 1H),? 7.04 baby mortality(d, J=8,1 Hz, 1H), 8,27(d, J=3.6 Hz, 1H), 9,80(user., 1H); 19F NMR(282 MHz, DMSO-d6): d - 152,34; LC/MS: retention time: RS 9.69 min; purity: 93,93%; MS(mass/charge): 282,12 (MH+).--
1118N4-(1-tert-Butoxycarbonylamino-3-yl)-5-fluoro-N2-(4-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(CDCl3): d 1,45(s, 9H), 3,18(t, J=4.8 Hz, 4H), to 3.89(m, 4H), of 3.96(m, 2H), 4,28(m, 2H), 4,69(m, 1H), 6,93(d, J=9.0 Hz, 2H), was 7.36(d, J=9,3 Hz, 2H), 7,66(d, J=3.6 Hz, 1H); 19F NMR(282 MHz, CDCl3): d - 163,92; LC/MS: retention time: 928 min; purity: 100%; MS (mass/charge): 445,25 (MH+).++
1119N2-[4-(4-Acetylpiperidine)phenyl]-N4-(1-tert-butoxycarbonylamino-3-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(CDCl3): d of 1.46(s, 9H), of 2.16(s, 3H), 3.15 in(p, J=5,1 Hz, 4H), to 3.64(t, J=5,1 Hz, 2H), 3,78(t, J=5,1 Hz, 2H), 3,91(DD, J=5,4, 9.9 Hz, 2H), 4,30(DD, J=7,8, and 9.6 Hz, 2H), 4,70(m, 1H), 6,91(d, J=9,3 Hz, 2H), 7,38(d, J=9,3 Hz, 2H), 7,72(d, J= 3.6 Hz, 1H); 19F NMR (282 MHz, CDCl3): d - 166,44; LC/MS: retention time: 8,48 min; purity: 91,50%; MS (mass/charge): 486,32 (MH+).+-
1120N2-[3-(4-Acetylpiperidine)phenyl]-N4-(1-tert-butoxycarbonylamino-3-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(CDCl3): d 1,45(s, 9H), of 2.16(s, 3H), 3,21(m, 4H), to 3.64(m, 2H), 3,78(m, 2H), 3,99(DD, J=4,8, 9,0 Hz, 2H), 4,30(DD, J=7,8, and 9.3 Hz, 2H), 4,74(m, 1H), 6.75 in(d, J=5,1 Hz, 1H), make 6.90(d, J=8.7 Hz, 1H), 7,19(m, 1H), 7,26(m, 1H), 7,69(d, J=42 Hz, 1H); 19F NMR (282 MHz, CDCl3): d - 162,80; LC/MS: retention time: 11,04 min; purity: 93,28%; MS (mass/charge): 486,31 (MH+).--
1121N4-(3-Cycloprop the l-1H-pyrazole-5-yl)-5-fluoro-N2-(4-morpholinomethyl)-2,4-pyrimidinediamine LC/MS: retention time: 7,80 min; purity: 96,17%; MS(mass/charge): 396,22(MH+).++-
1122N4-(1-tert-Butoxycarbonylamino-3-yl)-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 10,44 min; purity: 82,19%; MS(mass/charge): 516,26(MH+).+-
1123N4-(Azetidin-3-yl)-5-fluoro-N2-(4-morpholinomethyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,12 min; purity: 88,18%; MS(mass/charge): 345,21(MH+).-+
1124N2-[4-(4-Acetylpiperidine)phenyl]-N4-(azetidin-3-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 2,33 min; purity: 92,29%; MS(mass/charge): 386,25(MH+).--
1125 N4-(Azetidin-3-yl)-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 7,44 min; purity: 85,69%; MS(mass/charge): 416(MH+).--
1126N4-(Azetidin-3-yl)-5-fluoro-N2-(3-morpholinomethyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,85 min; purity: 100%; MS(mass/charge): 345,24(MH+).-+
1127N2-[3-(4-Acetylpiperidine)phenyl]-N4-(azetidin-3-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 3,10 min; purity: 88,30%; MS(mass/charge): 386,28(MH+).+-
1128N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(4-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 3.00(t, J=4.8 Hz, 4H), to 3.38(t, 2H), and 3.72(t, J=4.8 Hz, 4H), 4,08(t, J=4,2 Hz, 2H), 6,50(user., 1H), PC 6.82(d, J=9.0 Hz, 2H), 6,93(d, J=8,1 Hz, 1H), 7,20(d, J=8,1 Hz, 1H), of 7.48(d, J=9,3 Hz, 2H), to 7.99(d, J=3.6 Hz, 1H), 8,65((user. 1H), 8,92 (user. 1H); 19F NMR (282 is Hz, DMSO-d6): d - 164,78; LC/MS: retention time: 8,12 min; purity: 99,30%; MS (mass/charge): 424,25 (MH+).+-
1129N4-(1-tert-Butoxycarbonylamino-3-yl)-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 11,35 min; purity: 86,05%; MS(mass/charge): 516,32(MH+).-
1130N4-(Azetidin-3-yl)-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 8,39 min; purity: 96,94%; MS(mass/charge): 416(MH+).-
1131N4-(Azetidin-3-yl)-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 1,20 min; purity: 96,44%; MS(mass/charge): 358,24(MH+).-
1132 N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 3.38(t, 2H), 4,08(t, J=4.5 Hz, 2H), 6,52(user., 1H), 6,78(d, J=8,1 Hz, 1H), 7,27(m, 3H), 7,50(s, 1H), to 7.67(d, J=8,1 Hz, 1H), 8,01(s, 1H), 8,08(d, J=3.6 Hz, 1H), scored 8.38(s, 1H), 8,82(s, 1H), 9,35(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 162,94; LC/MS: retention time: to 9.32 min; purity: 100%; MS (mass/charge): 406,18 (MH+).+
11332-Chloro-N4-cyclobutyl-5-fluoro-N4-methyl-4-pyrimidinamine1H NMR(CDCl3): d by 1.68 to 1.76(m, 2H), 2,17 was 2.25(m, 4H), 3,14(d, J=3.0 Hz, 3H), 4,79(m, J=8,4 Hz, 1H), a 7.85(d, J=6.0 Hz, 1H); 19F NMR(282 MHz, CDCl3): d - 150,50; LC/MS: retention time: 13,83 min; purity: 96,47%; MS(mass/charge): 216,10(MH+).-
1134N2-[4-(4-Acetylpiperidine)phenyl]-N4-(3,4-dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 2,03(s, 3H), of 2.97(t, J=5,1 Hz, 2H), 3,03(t, J=5,1 Hz, 2H), 3,39(t, 2H), of 3.56(t, 4H), 4,08(t, J=4,2 Hz, 2H), 6,51(s, 1H), at 6.84(d, J=9.0 Hz, 2H), 6,93(d, J=8,4 Hz, 1H), 7,19(d, J=8,1 Hz, 1H), 7,49(d, J=9.0 Hz, 2H), to 7.99(d, J= 3.6 Hz, 1H), 8,67 (user. 1H), 8,95 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 164,68; LC/MS: retention time: 7,60 min; the number is PTA: 99,34%; MS (mass/charge): 465,30 (MH+).++
1135N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,19(t, J=7.2 Hz, 3H), 2,99(t, J=5.4 Hz, 4H), 3,39(t, 2H), 3,49(t, 4H), 4.04 the(sq, J=7.2 Hz, 2H), 4,08(t, J=4,8 Hz, 2H), 6,51(s, 1H), at 6.84(d, J=9,3 Hz, 2H), 6,93(d, J=8,4 Hz, 1H), 7,19(d, J=8,4 Hz, 1H), 7,49(d, J=9.0 Hz, 2H), to 7.99 (d, J= 3.6 Hz, 1H), 8,68 (user. 1H), 8,95 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 164,66; LC/MS: retention time: being 9.61 min; purity: 94,88%; MS (mass/charge): 495,31 (MH+).++
1136N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 2,99(t, J=5.1 Hz, 4H), 3,39(t, 2H), 3,69(t, J=4.8 Hz, 4H), 4,08(t, J=4,2 Hz, 2H), 6,50(m, 2H), 6,91(d, J=8,4 Hz, 1H),? 7.04 baby mortality(t, J=8,1 Hz, 1H), 7,19(m, 3H), of 8.04(d, J=3.6 Hz, 1H), a total of 8.74(s, 1H), of 9.02(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 163,64; LC/MS: retention time: 9,03 min; purity: 98,67%; MS (mass/charge): 424,26 (MH+).++
1137 N2-[3-(4-Acetylpiperidine)phenyl]-N4-(3,4-dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 2,03(s, 3H), 2,98(t, J=4,8 Hz, 2H), 3,05(t, J=4,8 Hz, 2H), 3,39(t, 2H), 3,53(t, J=5.4 Hz, 4H), 4,08(t, 2H), 6,50(m, 2H), 6,91(d, J=8,4 Hz, 1H),? 7.04 baby mortality(t, J=8,4 Hz, 1H), 7,21(m, 3H), of 8.04(d, J=3.6 Hz, 1H), up 8.75(s, 1H), 9,03 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 163,60; LC/MS: retention time: by 8.22 min; purity: 100%; MS (mass/charge): 465,25 (MH+).++
1138N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.20(t, J=7.2 Hz, 3H), 3,01(t, J=4.8 Hz, 4H), to 3.41(t, 2H), 3.46 in(t, J=4.8 Hz, 4H), 4,08(t, 2H), 6,50(m, 2H), 6,91(d, J=8,4 Hz, 1H),? 7.04 baby mortality(t, J=8,4 Hz, 1H), 7,19(d, J=8.1 Hz, 2H,), to 7.25(t, 1H), 8,04(d, J=3.6 Hz, 1H), 8,73(c, 1H), 9,02 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 163,61; LC/MS: retention time: 10,46 min; purity: 98,68%; MS (mass/charge): 495,25 (MH+).++
1139N4-Cyclobutyl-5-fluoro-N4-methyl-N2-(4-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,56 was 1.69(m, 2H), 2,07-of 2.27(m, 4H), of 3.07(t, J=4.5 Hz, 4H), 3,12(d, J=3.0 Hz, 3H), of 3.73(t, J=4.5 Hz, 4H), was 4.76(m, J=8,4 Hz, 1H), 6,92(d, J=9.0 Hz, 2), 7,42(d, J=8.7 Hz, 2H), of 7.97(d, J=7.2 Hz, 1H), 9,36(user., 1H); 19F NMR(282 MHz, DMSO-d6): d - 157,25; LC/MS: retention time: 9,50 min; purity: 100%; MS (mass/charge): 358,23 (MH+).+-
1140N2-[4-(4-Acetylpiperidine)phenyl]-N4-cyclobutyl-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,59 was 1.69(m, 2H), 2,03(s, 3H), 2,10-of 2.27(m, 4H), 3,03(t, J=4.5 Hz, 2H), 3,11(d, J=3.0 Hz, 5H), of 3.56(t, 4H), was 4.76(m, J=7.5 Hz, 1H), 6,93(d, J=9.0 Hz, 2H), 7,45(d, J=9.0 Hz, 2H), of 7.96(d, J=7.2 Hz, 1H), 9,26(user., 1H); LC/MS: retention time: 8,75 min; purity: 100%; MS (mass/charge): 399,28 (MH+).+-
1141N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 2.23(s, 3H), 3,03(t, 4H), 3,29(m, 4H), to 3.38(t, 2H), 4,08(t, J=4.5 Hz, 2H), 6,50(user., 1H), for 6.81(d, J=8.7 Hz, 2H), 6,92(d, J=8,4 Hz, 1H), 7,20(d, J=8,1 Hz, 1H), 7,46(d, J=9.0 Hz, 2H), 7,98(d, J=3.6 Hz, 1H), 8,64(user., 1H), 8,90 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 164,86; LC/MS: retention time: 5,58 min; purity: 100%; MS (mass/charge): 437 (MH+).++-
1142N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 2.20(s, 3H), 2,41(t, 4H), 3,03(t, 4H), to 3.38(t, 2H), 4,08(t, J=4,8 Hz, 2H), 6,50(m, 2H), 6,91(d, J=7.8 Hz, 1H), 7,02(t, J=7.8 Hz, 1H), 7,20(m, 3H), 8,03(d, J=3.6 Hz, 1H), 8,72(s, 1H), 8,99(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 163,72; LC/MS: retention time: 6,32 min; purity: 99.99 percent; MS (mass/charge): 437 (MH+).++-
1143N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 3.53(t, J=4,2 Hz, 2H), 4,16(t, J=4,2 Hz, 2H), at 6.84(d, J=8.7 Hz, 1H), 7,24(d, J=8.7 Hz, 1H), 7,35(s, 1H), 7,40(t, J=7.8 Hz, 1H), 7,56(dt, J=1,2, 8,1 Hz, 1H), 7,89(d, J=8,4 Hz, 1H), 8,18(s, 1H), 8,32(d, J=3.3 Hz, 1H), 8,44 (c, 1H), 10,35 (user. 2H); 19F NMR (282 MHz, DMSO-d6): d - 161,96; LC/MS: retention time: 9,54 min; purity: 98,01%; MS (mass/charge): 406,18 (MH+).++-
1144N4-(3-Cyclopropyl-1H-pyrazole-5-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 0,61-0,66(m, 2H), 0,86(m, 2H), is 1.81(m, 1H), 6,41(user., 1H), 7,35(m, 2H), 7,52(d, J=7.5 for the C, 1H), 7,86(s, 1H), 8,04(s, 1H), 8,19(m, 2H), 9,34(s, 1H), 9,60(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 163,42; LC/MS: retention time: 9,50 min; purity: 98,57%; MS (mass/charge): 378,20 (MH+).++-+
1145N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 3.49(t, 2H), 3,61(s, 3H), of 3.69(s, 6H), 4,14(t, J=4.5 Hz, 2H), 6,94(d, J=7.8 Hz, 1H), 7,07(s, 2H), 7,14(d, 1H), to 8.20(d, J=3.6 Hz, 1H), 9,75(s, 1H); LC/MS: retention time: 8,80 min; purity: 100%; MS(mass/charge): 429,45(MH+).++-+
1146N2-(3-Chloro-4-methoxyphenyl)-N4-(3,4-dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 3,39(s, 2H), of 3.78(s, 3H), 4,08(t, J=3,9 Hz, 2H), 6,54(user., 1H), 6,95(d, J=8,4 Hz, 1H), 7,00(d, J=8.7 Hz, 1H), 7,13(d, J=8,4 Hz, 1H), 7,46(DD, J=2,4, and 9.0 Hz, 1H), to 7.84(d, J=2.4 Hz, 1H), 8,04(d, J=3.3 Hz, 1H), 8,80(s, 1H), 9,16 (c, 1H); 19F NMR (282 MHz, DMSO-d6): d - 163,72; LC/MS: retention time: 10,31 min; purity: 99.90 percent; MS (mass/charge): 403,06 (MH+).+-
1147 N4-Cyclobutyl-5-fluoro-N4-methyl-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,56 by 1.68(m, 2H), 2,10-of 2.26(m, 4H), of 2.21(s, 3H), 2,44(t, 4H), to 3.02(t, J=4.8 Hz, 4H), 3,05(d, J=2.7 Hz, 3H), 4,74(m, J=7.8 Hz, 1H), PC 6.82(d, J=9.0 Hz, 2H), 7,49(d, J=8.7 Hz, 2H), 7,88(d, J=6,6 Hz, 1H), 8,79(user., 1H); 19F NMR (282 MHz, DMSO-d6): d - 159,83; LC/MS: retention time: 6.35mm min; purity: 95,87%; MS (mass/charge): 371,21 (MH+).++-+
1148N4-Cyclobutyl-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,19(t, J=7.2 Hz, 3H), 1.56 to 1.69 in(m, 2H), 2,07-of 2.27(m, 4H), 3,06(t, J=4.8 Hz, 4H), 3,11(d, J=3.0 Hz, 3H), 3,50(t, 4H), 4,05(sq, J=7.2 Hz, 2H), amounts to 4.76(m, J=8,4 Hz, 1H), 6,93(d, J=9.0 Hz, 2H), 7,43(d, J=8.7 Hz, 2H), of 7.97(d, J= 7.5 Hz, 1H), was 9.33 (user. 1H); LC/MS: retention time: 11,06 min; purity: 96,72%; MS (mass/charge): 429,45 (MH+).++-
149N4-Cyclobutyl-5-fluoro-N4-methyl-N2-(3-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,57 is 1.70(m, 2H), 2,13-of 2.24(m, 4H), of 3.07(t, J=4.8 Hz, 4H), 3,11(d, J=3.3 Hz, 3H), of 3.73(t, J=4.5 Hz, 4H), 4,78(m, J=8.7 Hz, 1H), to 6.57(m, 1H), was 7.08(m, 2H), 7,24(m, 1H), 7,98(d, J=6,9 Hz, 1H), 9,19(user., 1H); LC/MS: time derivan is: 10,46 min; purity: 97,98%; MS (mass/charge): 358,34 (MH+).+-
1150N2-[3-(4-Acetylpiperidine)phenyl]-N4-cyclobutyl-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(CDCl3): d 1,66-of 1.78(m, 2H), of 2.15(s, 3H), 2,22(m, 4H), 3,17(d, J=2.7 Hz, 3H), up 3.22(m, 4H), 3,62(t, J=4,8 Hz, 2H), of 3.77(t, J=5,1 Hz, 2H), 4,85(m, J=8,4 Hz, 1H), return of 6.58(DD, J=2,4, 8,1 Hz, 1H),? 7.04 baby mortality(d, J=8,4 Hz, 1H), 7,19(t, J=8,1 Hz, 1H), 7,24 (d, J= 8,1 Hz, 1H), 7,53 (user. 1H), of 7.75 (d, J= 6,9 Hz, 1H); 19F NMR (282 MHz, CDCl3): -157,20; LC/MS: retention time: 9,37 min; purity: 87,43%; MS (mass/charge): 399,56 (MH+).+-
1151N4-Cyclobutyl-5-fluoro-N4-methyl-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(CDCl3): d and 1.63-1.77 in(m, 2H), of 2.21(m, 4H), of 2.45(s, 3H), of 2.72(t, J=4.8 Hz, 4H), 3,13(d, J=3,9 Hz, 3H), 3,32(t, J=4.8 Hz, 4H), 4,84(m, J=8.7 Hz, 1H), 6,56(DD, J=2,4, 8,1 Hz, 1H), 6,82(user., 1H), 7,00(d, J=8,1 Hz, 1H), 7,17(t, J=7.8 Hz, 1H), 7,25 (d, J= 1.5 Hz, 1H), 7,80 (d, J= 6,6 Hz, 1H); 19F NMR (282 MHz, CDCl3): -158,30; LC/MS: retention time: 7,27 min; purity: 87,72%; MS (mass/charge): 371,20 (MH+).++-
1152 N4-Cyclobutyl-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,19(t, J=7.2 Hz, 3H), 1,60-1,70(m, 2H), 2,13-of 2.28(m, 4H), is 3.08(t, J=5.1 Hz, 4H), 3,12(d, J=3.3 Hz, 3H), 3,50(t, 4H), 4,05(sq, J=7.2 Hz, 2H), 4,79(m, J=9.0 Hz, 1H), 6,59(d, J=6,9 Hz, 1H), to 7.09(m, 2H), 7,27(s, 1H), to 7.99 (d, J= 6,9 Hz, 1H), 9,27 (user. 1H); LC/MS: retention time: 11,92 min; purity: 99,18%; MS (mass/charge): 429,22 (MH+).+-
1153N2-(2-Aminocarbonyl-5-benzoxa-4-methoxyphenyl)-N4-cyclobutyl-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,69-of 1.78(m, 2H), 2,28(m, 4H), to 3.36(d, J=3.3 Hz, 3H), 3,90(s, 3H), 4,94(m, 1H), and 5.30(s, 2H), 7,12(s, 1H), 7,35-of 7.48(m, 6H), 9,04(d, J=9.0 Hz, 1H); LC/MS: retention time: 11,25 min; purity: 98,01%; MS(mass/charge): 435,22(M-16).--
1154N2-(4-Benzamidophenyl)-N4-cyclobutyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,62-of 1.74(m, 2H), 2,02-of 2.15(m, 2H), 2.23 to-2,31(m, 2H), 4,50(m, J=8,1 Hz, 1H), 7,46-to 7.68(m, 8H), to 7.84(d, J=3.6 Hz, 1H), 7,92(TD, J=1,2, and 6.6 Hz, 2H), 8,99(s, 1H), 10,07(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 167,01; LC/MS: retention time: 9,59 min; purity: 94,19%; MS (mass/charge): 378,50 (MH+).-
1155N4-Cyclopentyl-5-fluoro-N2-(4-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d and 1.54(m, 4H), to 1.70(m, 2H), was 1.94(m, 2H), 2,98(t, J=4.8 Hz, 4H), 3,70(t, J=4.8 Hz, 4H), 4,30(sq, J=6,9 Hz, 1H), 6,80(d, J=9.0 Hz, 2H), 7,22(d, J=6,9 Hz, 1H), 7,55(d, J=9,3 Hz, 2H,), 7,76(d, J=3.6 Hz, 1H), total of 8.74(user., 1H); 19F NMR (282 MHz, DMSO-d6): d - 167,62; LC/MS: retention time: 8,98 min; purity: 99,38%; MS (mass/charge): 358,18 (MH+).+-
1156N2-[4-(4-Acetylpiperidine)phenyl]-N4-cyclopentyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d and 1.54(m, 4H), to 1.70(m, 2H), 1.93 and(m, 2H), 2,02(s, 3H), equal to 2.94(t, J=4,8 Hz, 2H), 3,01(t, J=5,1 Hz, 2H), 3,54(t, 4H), 4,30(sq, J=6,9 Hz, 1H), 6,83(d, J=8.7 Hz, 2H), 7,24(d, J=7,2 Hz, 1H), 7,56(d, J=9.0 Hz, 2H), 7,76(d, J=3,9 Hz, 1H), 8,76 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 167,53; LC/MS: retention time: 8,28 min; purity: 98,08%; MS (mass/charge): 399,20 (MH+).+-
1157N4-Cyclopentyl-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,4(m, 4H), to 1.70(m, 2H), 1.93 and(m, 2H), of 2.21(s, 3H), 2,44(t, 4H), 3,01(t, 4H), 4,30(sq, J=6.3 Hz, 1H), 6,79(d, J=8.7 Hz, 2H), 7,22(d, J=6.3 Hz, 1H), 7,53(d, J=9.0 Hz, 2H), 7,76(d, J=3.0 Hz, 1H), 8,72(user., 1H); 19F NMR(282 MHz, DMSO-d6): d - 167,68; LC/MS: retention time: of 5.53 min; purity: 83,38%; MS (mass/charge): 371,08 (MH+).+-
1158N4-Cyclopentyl-5-fluoro-N2-(3-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.52(m, 4H), 1,71(m, 2H), 1.93 and(m, 2H), 3,03(t, J=4.8 Hz, 4H), and 3.72(t, J=4.8 Hz, 4H), 4,36(m, 1H), 6,45(d, J=9.6 Hz, 1H), 7,02(t, J=7.8 Hz, 1H), 7,13(d, J=8,1 Hz, 1H), 7,31(d, J=7.2 Hz, 1H), 7,42(s, 1H), 7,80(d, J=3.6 Hz, 1H), 8,84 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 166,77; LC/MS: retention time: 9,54 min; purity: 90,50%; MS (mass/charge): 358,20 (MH+).+-
1159N2-[3-(4-Acetylpiperidine)phenyl]-N4-cyclopentyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.53(m, 4H), 1,71(m, 2H), was 1.94(m, 2H), 2,03(s, 3H), to 3.02(t, J=5,1 Hz, 2H), is 3.08(t, J=4,8 Hz, 2H), 3,55(t, 4H), 4,36(sq, J=6,6 Hz, 1H), 6,47(d, J=7.8 Hz, 1H), 7,03(t, J=8,1 Hz, 1H), 7,14(d, J=7.8 Hz, 1H), 7,30(d, J=7.2 Hz, 1H), 7,44 (c, 1H), 7,80 (d, J= 3.6 Hz, 1H), 8,84 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 166,76; LC/MS: retention time: at 8.60 min; purity: 97,49%; MS (mass/charge): 399,48 MH+). +-
1160N4-Cyclopentyl-5-fluoro-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: of 6.49 min; purity: 79,17%; MS(mass/charge): 371,23(MH+).+-
1161N4-Cyclopentyl-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 10,76 min; purity: 77,07%; MS(mass/charge): 429,50(MH+).+-
1162N4-Cyclohexyl-5-fluoro-N2-(4-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,14(m, 1H), 1,31(m, 4H), 1,64(d, 1H), about 1.75(m, 2H), 1,90(m, 2H), 2,98(t, J=4.8 Hz, 4H), 3,71(t, J=4.8 Hz, 4H), 3,86(m, 1H), 6,80(d, J=9,3 Hz, 2H), 7,14(d, J=8,4 Hz, 1H), 7,55(d, J=9.0 Hz, 2H), 7,76(d, J=3,9 Hz, 1H), total of 8.74 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 167,70; LC/MS: retention time: 9,48 min; purity: 100%; MS (mass/charge): 372,45 (MH+).+-
1163N2-[4-(4-Acetylpiperidine)phenyl]-N4-cyclohexyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d is 1.31(m, 5H), 1,64(d, 1H), about 1.75(m, 2H), 1,90(m, 2H), 2,02(s, 3H), equal to 2.94(t, J=4,8 Hz, 2H), 3,01(t, J=5,1 Hz, 2H), 3,55(m, 4H), 3,86(m, 1H), PC 6.82(d, J=9.0 Hz, 2H), 7,12(d, J=7.5 Hz, 1H), 7,55(d, J=8.7 Hz, 2H), 7,76(d, J=3,9 Hz, 1H), 8,75 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 167,64; LC/MS: retention time: 8,62 min; purity: 99.89 per cent; MS (mass/charge): 413,44 (MH+).+-
1164N4-Cyclohexyl-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d is 1.31(m, 5H), 1,64(d, 1H), about 1.75(m, 2H), 1,90(m, 2H), of 2.21(s, 3H), 2,46(t, J=4.8 Hz, 4H), 3,01(t, J=4.8 Hz, 4H), 3,85(m, 1H), 6,79(d, J=9.0 Hz, 2H), 7,12(d, J=8,4 Hz, 1H), 7,52(d, J=9.0 Hz, 2H), 7,76(d, J=3,9 Hz, 1H), 8,72 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 167,78; LC/MS: retention time: 6,09 min; purity: 99,06%; MS (mass/charge): 385,20 (MH+).+-+
1165N4-Cyclohexyl-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,19(t, J=7.2 Hz, 3H), 1,31(m, 5H), 1,64(d, 1H), 1,76(m, 2H), 1,90(m, 2H), 2,97(t, J=4.8 Hz, 4H),3,48(t, 4H), 3,86(m, 1H), 4.04 the(sq, J=7.2 Hz, 2H), PC 6.82(d, J=9.0 Hz, 2H), 7,12(d, J=6,9 Hz, 1H), 7,55(d, J=9,3 Hz, 2H), 7,76 (d, J= 3,9 Hz, 1H), 8,75 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 167,63; LC/MS: retention time: 10,75 min; purity: 98,19%; MS (mass/charge): 443,19 (MH+).++
1166N4-Cyclohexyl-5-fluoro-N2-(3-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.27(m, 5H), and 1.63(d, 1H), 1,76(m, 2H), to 1.87(m, 2H), 3.04 from(t, J=4.8 Hz, 4H), and 3.72(t, J=4.8 Hz, 4H), 3,90(m, 1H), 6,46(DD, J=2.1 a, and 7.8 Hz, 1H), 7,03(t, J=8,4 Hz, 1H), 7,16(d, J=7,8 Hz, 1H), 7,24(m, 2H), 7,80(d, J=3,9 Hz, 1H), 8,78 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 166,81; LC/MS: retention time: 10,22 min; purity: 99,24%; MS (mass/charge): 372,15 (MH+).+-
167N2-[3-(4-Acetylpiperidine)phenyl]-N4-cyclohexyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d is 1.31(m, 5H), to 1.61(m, 1H), 1,76(m, 2H), to 1.87(m, 2H), 2,03(s, 3H), 3.04 from(t, 2H), to 3.09(t, 2H), of 3.56(t, 4H), 3,90(m, 1H), 6.48 in(d, J=9.0 Hz, 1H),? 7.04 baby mortality(t, J=8,4 Hz, 1H), 7,17(d, J=8,4 Hz, 1H), 7,25(m, 2H), 7,80(d, J=3.6 Hz, 1H), 8,80 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 166,78; LC/MS: retention time: 9,31 min; purity: 93,22%; MS (mass/charge): 413,19 (MH+).+ -
1168N4-Cyclohexyl-5-fluoro-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,14(m, 1H), 1,31(m, 4H), and 1.63(d, 1H), 1,76(m, 2H), to 1.86(m, 2H), and 2.26(s, 3H), to 3.09(t, 4H), of 3.32(t, 4H), 3,88(m, 1H), 6,45(d, J=6,9 Hz, 1H), 7,01(t, J=8,1 Hz, 1H), 7,16(d, J=7.2 Hz, 1H), 7,24(m, 2H), 7,80(d, J=3,9 Hz, 1H), 8,76 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 166,84; LC/MS: retention time: 7,16 min; purity: 96,05%; MS (mass/charge): 385,27 (MH+).+-
1169N4-Cyclohexyl-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,19(t, J=6.9 Hz, 3H), 1,31(m, 5H), of 1.62(d, 1H), 1,76(m, 2H), to 1.87(m, 2H), 3,05(t, J=4.8 Hz, 4H), to 3.49(t, 4H), 3,90(m, 1H), 4,05(sq, J=7.2 Hz, 2H), 6.48 in(d, J=4.5 Hz, 1H), 7.03 is(t, J=8,1 Hz, 1H), 7,16(d, J=6,6 Hz, 1H), 7,24 (d, J= 8.7 Hz, 1H), 7,28 (c, 1H), 7,80 (d, J= 3,9 Hz, 1H), 8,80 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 166,76; LC/MS: retention time: 11,50 min; purity: of 85.32%; MS (mass/charge): 442,95 (MH+).+-
1170N2-(4-Benzamidophenyl)-N4-cyclopentyl-5-fluoro-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d of 1.57(m, 4H), 1,72(m, 2H), 1,96(m, 2H), 4,32(sq, J=7.5 Hz, 1H), 7,29(d, J=6.3 Hz, 1H), 7,46-of 7.69(m, 7H), 7,81(d, J=3,9 Hz, 1H), 7,92(d, J=9.6 Hz, 2H), 8,97(s, 1H), of 10.05(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 166,85; LC/MS: retention time: 10,15 min; purity: 97,75%; MS (mass/charge): 392,16 (MH+).+-
1171N2-(2-Aminocarbonyl-5-benzoxa-4-methoxyphenyl)-N4-cyclopentyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 1.60(m, 4H), of 1.74(m, 2H), 1,96(m, 2H), 3,85(s, 3H), 4,43(sq, J=6,9 Hz, 1H), 5,24(s, 2H), 7,06(s, 1H), 7,31-to 7.50(m, 6H), 8,53(d, J=7.2 Hz, 1H), to 8.70(d, J=6,9 Hz, 1H); 19F NMR(282 MHz, DMSO-d6): d - 155,92; LC/MS: retention time: 11,18 min; purity: 96,52%; MS (mass/charge): 435,16 (M-16).+-
1172N2-[4-(N-Acetyl-N-methylamino)phenyl]-N4-cyclopentyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.55(m, 4H), 1,71(m, 2H), was 1.94(m, 2H), to 3.09(s, 3H), and 3.31(s, 3H), 4,32(sq, J=7.2 Hz, 1H), 7,13(d, J=9.0 Hz, 2H), 7,34(d, J=7.2 Hz, 1H), to 7.77(d, J=8.7 Hz, 2H), 7,83(d, J=3,9 Hz, 1H), 9,14(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 166,12; LC/MS: retention time: 8.34 per min; purity: 97,77%; MS (mass/charge): 344,13 (MH+).+-
1173N4-Cyclopentyl-5-fluoro-N2-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.55(m, 4H), 1,71(m, 2H), 1.93 and(m, 2H), 3,62(s, 4H), or 4.31(sq, J=6,6 Hz, 1H), of 6.71(d, J=7.8 Hz, 1H), 7,25(t, J=7.8 Hz, 1H), 7,40(d, J=7.2 Hz, 1H), 7,53(d, J=7.5 Hz, 1H), 7,84(, 2H), by 8.22(s, 1H), 9,23(s, 1H), 10,54(user., 1H); 19F NMR (282 MHz, DMSO-d6): d - 165,78; LC/MS: retention time: 5,71 min; purity: 92,06%; MS (mass/charge): 356,17 (MH+).--
1174N2-(4-Benzamidophenyl)-N4-cyclohexyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.33(m, 5H), of 1.65(d, 1H), 1,78(m, 2H), 1,92(m, 2H), 3,88(m, 1H), 7,22(d, J=8,1 Hz, 1H), 7,46-of 7.69(m, 7H), 7,81(d, J=3,9 Hz, 1H), 7,92(d, J=6.6 Hz, 2H), 8,99(s, 1H), of 10.05(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 166,98; LC/MS: retention time: 10,79 min; purity: 94,61%; MS (mass/charge): 406,43 (MH+).-+-+
1175N2-(2-Aminocarbonyl-5-benzoxa-4-methoxyphenyl)-N4-cyclohexyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.36(m, 5H), of 1.65(d, 1H), 1,79(m, 2H), of 1.88(m, 2H), 3,85(s, 3H), of 4.05(m, 1H), 5,24(s, 2H), 7,06(s, 1H), 7,31-to 7.50(m, 6H), 8,44(d, J=7.5 Hz, 1H), to 8.70(d, J=6,9 Hz, 1H); 19F NMR(282 M is C, DMSO-d6): d - 156,00; LC/MS: time odergivaniya,66 min; purity: 98,19%; MS (mass/charge): 449,43 (M-16).+-
1176N2-[4-(N-Acetyl-N-methylamino)phenyl]-N4-cyclohexyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,32(m, 5H), 1,64(d, 1H), 1,74(m, 2H), 1,90(m, 2H), to 3.09(s, 3H), of 3.32(s, 3H), 3,88(m, 1H), 7,13(d, J=8,4 Hz, 2H), 7,26(d, J=7.5 Hz, 1H), of 7.75(d, J=8.7 Hz, 2H), 7,83(d, J=3,9 Hz, 1H), 9.15, with(s, 1H); 19F NMR(282 MHz, DMSO-d6): d - 166,21; LC/MS: retention time: 8,97 min; purity: 100%; MS (mass/charge): 358,18 (MH+).+-
1177N4-Cyclohexyl-5-fluoro-N2-[3-(N-2-imidazolin-2-yl)AMINOPHENYL]-2,4-pyrimidinediamineLC/MS: retention time: 6.42 per min; purity: 86,49%; MS(mass/charge): 370,47(MH+).--
1178N2,N4-Bis[3-(oxazol-2-yl)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 7,22(t, J=7.8 Hz, 1H), 7,31(d, J=9,3 Hz, 2H), 7,40(t, J=8,1 Hz, 1H), 7,46(d, J=7.5 Hz, 1H), to 7.64(d, J=7.5 Hz, 1H), 7,81(d, J=7.8 Hz, 1H), 8,08(d, J=7.5 Hz, 1H), 8,11(d, 2H),8,18(d, J=3.6 Hz, 1H), 8,24(t, J=1.8 Hz, 1H), 8,29 (t, 1H), 9,48 (c, 1H), 9,60 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 162,99; LC/MS: retention time: 11,53 min; purity: 95,22%; MS (mass/charge): 415,02 (MH+).--
1179N4-Cyclobutyl-5-fluoro-N4-methyl-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,53-1,71(m, 2H), 2,11 of-2.32(m, 4H), and 3.16(d, J=3,6 Hz, 3H), 4,89(m, J=8,4 Hz, 1H), was 7.36(d, J=0.9 Hz, 1H), 7,40(t, J=7.8 Hz, 1H), EUR 7.57(m, 2H), of 8.06(d, J=7.2 Hz, 1H), to 8.20(d, J=the 0.9 Hz, 1H), to 8.57(t, J=1.8 Hz, 1H), 9,68(s, 1H); 19F NMR (282 MHz, DMSO-d6): d - 156,69; LC/MS: retention time: 11,99 min; purity: 95,24%; MS (mass/charge): 340,18 (MH+).+-
1180(S)-N4-(1-Benzylpyrrolidine-3-yl)-5-fluoro-N2-(4-morpholinomethyl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d to 1.83(m, 1H), 2,16(m, 1H), 2.40 a(DD, J=5,1, 9,3 Hz, 1H), 2,58(m, 2H), 2,89(DD, J=7,2, 9,3 Hz, 1H), 2,99(t, J=4.8 Hz, 4H), to 3.58(d, J=1.8 Hz, 2H), and 3.72(t, J=4.8 Hz, 4H), to 4.41(m, 1H)that is 6.78(d, J=9.0 Hz, 2H), 7,22(m, 1H), 7, 22 (m, 1H), 7,29 (m, 4H), 7,35 (d, J= 6,6 Hz, 1H), 7,50 (d, J= 8.7 Hz, 2H), to 7.77 (d, J= 3,9 Hz, 1H), 8,73 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 167,51; LC/MS: retention time: 5,99 min; purity: 99,07%; MS (mass/charge): 449 (MH+).+ -
1181(S)-N2-[4-(4-Acetylpiperidine)phenyl]-N4-(1-benzylpyrrolidine-3-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,81-to 1.87(m, 1H), 2,03(s, 3H), 2,14-of 2.23(m, 1H), 2.40 a(DD, J=5,7, and 9.6 Hz, 1H), has 2.56(m, 2H), 2,89(DD, J=7,2, 9,3 Hz, 1H), 2.95 points(t, J=5,1 Hz, 2H), to 3.02(t, J=5,1 Hz, 2H), 3,55(m, 4H), to 3.58(s, 2H), to 4.41(m, 1H), for 6.81(d, J=9.0 Hz, 2H), 7,22 (m, 1H), 7,29 (m, 4H), 7,35 (d, J= 6.3 Hz, 1H), 7,51 (d, J= 9,3 Hz, 2H), 7,78 (d, J= 3,9 Hz, 1H), 8,75 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 167,42; LC/MS: retention time: 5,81 min; purity: 97,77%; MS (mass/charge): 490,27 (MH+).+-
1182(S)-N4-(1-Benzylpyrrolidine-3-yl)-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 1,17 min; purity: 95,41%; MS(mass/charge): 462,15(MH+).--

1230
1183(S)-N4-(1-Benzylpyrrolidine-3-yl)-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,19(t, J=7.2 Hz, 3H)and 1.83(m, 1H), 2,17(m, 1H), 2.40 a(DD, J=5,1, ,0 Hz, 1H), has 2.56(m, 2H), 2,89(DD, J=7,2, 9.0 Hz, 1H), 2,98(t, J=5.1 Hz, 4H), 3,49(t, J=5.1 Hz, 4H), to 3.58(d, J=1.8 Hz, 2H), 4,05(sq, J=7.2 Hz, 2H), of 4.44(m, 1H), 6,80 (d, J= 9.0 Hz, 2H), 7,22 (m, 1H), 7,28 (d, 4H), 7,35 (d, J= 6,6 Hz, 1H), 7,50 (d, J= 9,3 Hz, 2H), to 7.77 (d, J= 3,9 Hz, 1H), 8,75 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 167,41; LC/MS: retention time: 7,42 min; purity: 95,27%; MS (mass/charge): 520,22 (MH+).+-
1184(S)-N4-(1-Benzylpyrrolidine-3-yl)-5-fluoro-N2-(3-morpholinomethyl)-2,4-pyrimidinediamineLC/MS: retention time: for 6.81 min; purity: 100%; MS(mass/charge): 449(MH+).+-
1185(S)-N2-[3-(4-Acetylpiperidine)phenyl]-N4-(benzylpyrrolidine-3-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,82-of 1.88(m, 1H), 2,02(s, 3H), 2,16-of 2.26(m, 1H), 2,37(DD, J=5,7, and 9.0 Hz, 1H), has 2.56(m, 2H), 2,92(DD, J=6,9, and 9.0 Hz, 1H), 3,03(t, J=5,1 Hz, 2H), 3,10(t, J=5,1 Hz, 2H), of 3.56(m, 4H), to 3.58(s, 2H), 4.53-in(m, 1H), 6,47(d, J=8,4 Hz, 1H), 7,02 (t, J= 8,1 Hz, 1H), 7,10 (d, J= 8,4 Hz, 1H), 7,21 (m, 1H), 7,28 (m, 4H), 7,46 (m, 2H), 7,82 (d, J= 3,9 Hz, 1H), 8,87 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 166,63; LC/MS: retention time: to 6.43 min; purity: 94,97%; MS (mass/charge): 490,40 (MH+).+ -
1186(S)-N4-(1-Benzylpyrrolidine-3-yl)-5-fluoro-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 2,79 min; purity: 97,87%; MS(mass/charge): 462(MH+).+-
1187(S)-N4-(1-Benzylpyrrolidine-3-yl)-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 1.18(t, J=7.2 Hz, 3H), equal to 1.82(m, J=6,5 Hz, 1H), 2,19(m, 1H), 2,37(DD, J=5,7, and 9.0 Hz, 1H), has 2.56(m, 2H), 2.91 in(DD, J=7,2, 9.0 Hz, 1H), 3,06(t, J=5.1 Hz, 4H), 3,51(t, J=5.1 Hz, 4H), to 3.58(s, 2H), 4.04 the(sq, J=7.2 Hz, 2H), 4,55(m, 1H), 6,46 (d, J= 7.2 Hz, 1H), 7,02 (t, J= 7.8 Hz, 1H), 7,07 (d, J= 7.5 Hz, 1H), 7,22 (m, 1H), 7,27 (m, 4H), 7,47 (m, 2H), 7,82 (d, J= 3,9 Hz, 1H), 8,86 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - to 166.66; LC/MS: retention time: 8,25 min; purity: 97,24%; MS (mass/charge): 520,41 (MH+).+-
1188N4-Cyclobutyl-5-fluoro-N2-[3-chloro-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,61-of 1.73(m, 2H), 2,01 with 2.14(m, 2H), 2,25 is 2.33(m, 2H), to 2.29(s, 3H), by 2.55(m, 4H), 2.91 in(t, 4H), 4,47(m, J=8,1 Hz, 1H), 7,03(d, J=8.7 Hz, 1H), 7,43(DD, J=2.7, and 9.0 Hz, 1H), 7,69(d, J=,2 Hz, 1H), to 7.84(d, J=3.6 Hz, 1H), 8,07 (d, J= 2.4 Hz, 1H), remaining 9.08 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 166,50; LC/MS: retention time: 11,07 min; purity: 93,70%; MS (mass/charge): 391,10 (MH+).+
1189N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine salt of bis-p-toluensulfonate acid1H NMR(DMSO-d6): d of 2.28(s, 6H), 2,86(d, J=4,8 Hz, 3H), of 2.92(m, 2H), 3,13(sq, J=10,8 Hz, 2H), 3,49(m, 4H), 3,74(d, J=13,2 Hz, 2H), 4,15(t, J=4,2 Hz, 2H), 6,66(d, J=7.8 Hz, 1H), of 6.96(d, J=8.7 Hz, 1H), was 7.08(d, J=8,4 Hz, 4H), 7,17(m, 4H), 7,45 (d, J= 8.1 Hz, 4H), 8,19 (d, J= 3.6 Hz, 1H), 9,42 (user. 1H), 9,51 (user. 1H), 9,95 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 162,24; LC/MS: retention time: 1,60 min; purity: being equal to 98.21 per%; MS (mass/charge): 436,77 (MH+).++
1190N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine bis-cleaners containing hydrochloride salt1H NMR(DMSO-d6): d of 2.81(d, J=4.5 Hz, 3H), is 3.08(m, 4H), 3,48(d, J=11.7 Hz, 2H), 3,55(t, 2H), and 3.72(d, J=11.7 Hz, 2H), 4,18(t, J=4,2 Hz, 2H), 6,65(d, J=9.0 Hz, 1H), 6,74(d, J=8,1 Hz, 1H), 7,15(t, J=8,1 Hz, 1H), was 7.36(d, J=8,1 Hz, 1H), 7,41 (m, 2H), 8,30 (d, J= 3.3 Hz, 1H), 10,45 (user. 1H), 10,59 (user. 1H), of 10.72 (the Shire. 1H); 19F NMR (282 MHz, DMSO-d6): d - 162,32; LC/MS: retention time: 1,51 min; purity: 100%; MS (mass/charge): 437,08 (MH+).++
1191N2-[3-Chloro-4-(4-methylpiperazine)phenyl]-N4-cyclohexyl-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 1,14(m, 1H), 1,33(m, 4H), and 1.63(d, 1H), 1,74(m, 2H), 1,90(m, 2H), of 2.21(s, 3H), of 2.45(m, 4H), 2,88(t, 4H), to 3.89(m, 1H), 7,01(d, J=8.7 Hz, 1H), 7,24(d, J=7.8 Hz, 1H), 7,39(DD, J=2,4, and 8.4 Hz, 1H), 7,81(d, J=3,9 Hz, 1H), 8, 03 (d, J= 2.1 Hz, 1H), 9,05 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 166,45; LC/MS: retention time: 1.57 in min; purity: 96,83%; MS (mass/charge): 419,15 (MH+).++
1192N2-[4-(4-Acetylpiperidine)phenyl]-N4-cyclobutyl-5-fluoro-2,4-pyrimidinediamine bis-cleaners containing hydrochloride salt1H NMR(DMSO-d6): d of 1.65 to 1.76(m, 2H), 2,04(s, 3H), 2,08-of 2.26(m, 4H), 3,10(t, 2H), 3,17(t, 2H), to 3.58(t, 4H), 4,43(m, J=7.8 Hz, 1H), 7,02(d, J=8.1 Hz, 2H), 7,37(d, J=8,4 Hz, 2H), 8,00(d, J=5,1 Hz, 1H), 9,10(user., 1H), 10,02(user., 1H); 19F NMR(282 MHz, DMSO-d6): d - 162,88; LC/MS: retention time: 15,12 min; purity: 97,62%; MS (mass/charge): 385,16 (MH+).+
1193N4-Cyclohexyl-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine salt of bis-p-toluensulfonate acid1H NMR(DMSO-d6): d 1,24(m, 4H), 1,37(square, 1H), 1,62(d, 1H), 1,76(d, 2H), 1,85(d, 2H), 2,28(s, 6H), 2,86(d, J=3,9 Hz, 3H), of 2.92(d, 2H), 3.15 in(m, 2H), 3,52(d, 2H), 3,80(d, 3H), 7,00(d, J=9,3 Hz, 2H), to 7.09(d, J=7.8 Hz, 4H), of 7.36(d, J=9,3 Hz, 2H), 7,45 (d, J= 8.1 Hz, 4H), 8,01 (d, J= 6.0 Hz, 1H), 8,94 (user. 1H), at 9.53 (user. 1H), 9,92 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 162,18; LC/MS: retention time: 1,52 min; purity: of 99.98%; MS (mass/charge): 384,89 (MH+).+
1194N4-Cyclohexyl-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine bis-cleaners containing hydrochloride salt1H NMR(DMSO-d6): d of 1.33(m, 5H), to 1.61(d, 1H), 1.77 in(d, 2H), 1,87(d, 2H), and 2.79(d, J=4,8 Hz, 3H), to 3.09(m, 4H), 3,47(d, 2H), 3,78(d, 2H), 3,83(m, 1H), 7,01(d, J=9.0 Hz, 2H), 7,39(d, J=9.0 Hz, 2H), 8,10(d, J=5.4 Hz, 1H), remaining 9.08(d, J=8,1 Hz, 1H), 10,46 (user. 1H), 10,91 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 161,93; LC/MS: retention time: 1,55 min; purity: 99,46%; MS (mass/charge): 385,20 (MH+).,+
1195N2-[3-Chloro-4-(4-methylpiperazine)phenyl]-N4-cyclopentyl-5-fluoro-2,pyrimidinediamine 1H NMR(DMSO-d6): d of 1.55(m, 4H), 1,71(m, 2H), up to 1.98(m, 2H), 2,31(s, 3H), 2.57 m(m, 4H), 2.91 in(t, 4H), 4,30(sq, J=6,9 Hz, 1H), 7,03(d, J=8.7 Hz, 1H), was 7.36(d, J=6,9 Hz, 1H), 7,43(DD, J=2.7, and 9.0 Hz, 1H), of 7.82(d, J=3,9 Hz, 1H), 8,07(d, J=2.4 Hz, 1H), remaining 9.08 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 166,32; LC/MS: retention time: 13,47 min; purity: 87,25%; MS (mass/charge): 405,47 (MH+).+
1196N2-[3-Chloro-4-(4-methylpiperazine)phenyl]-N4-(3-cyclopropyl-1H-pyrazole-5-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 0.69(m, 2H), of 0.91(m, 2H), 1,87(m, 1H), 2,22(s, 3H), 2,46(m, 4H), 2,90(t, 4H), of 6.31(user., 1H),? 7.04 baby mortality(d, J=9.0 Hz, 1H), 7,51(user., 1H), 7,79(s, 1H), 8,02(s, 1H), 9,14(user., 1H), 9,52(user., 1H), 12,07(user., 1H); 19F NMR(282 MHz, DMSO-d6): d - 164,15; LC/MS: retention time: 1,65 min; purity: 92,40%; MS (mass/charge): 443,15 (MH+).+
1197N2-[3-Chloro-4-(4-methylpiperazine)phenyl]-N4-(3,4-dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 2.21(s, 3H), of 2.45(t, 4H), 2,88(t, 4H), 3,39(m, 2H), 4.09 to(t, J=4,2 Hz, 2H), 6,53(s, 1H), 6,94(d, J=8.7 Hz, 1H), 7,01(d, J=8.7 Hz, 1H), 7,12(d, J=8,4 Hz, 1H), 7,46(DD, J=2.7, and to 8.7 Hz, 1H), to 7.84(d, J=2.7 Hz, 1H), 8,04(d, J= 3.6 Hz, 1H), 8,80 (c, 1H), 9,20 (c, 1H); 19F NMR (282 is Hz, DMSO-d6): d - 163,49; LC/MS: retention time: 1,60 min; purity: 98,82%; MS (mass/charge): 471,12 (MH+).++
1198N2-[3-Chloro-4-(4-methylpiperazine)phenyl]-N4-cyclobutyl-5-fluoro-2,4-pyrimidinediamine bis-cleaners containing hydrochloride salt1H NMR(DMSO-d6): d 1,67 to 1.76(m, 2H), 2,11-to 2.18(m, 2H), 2,25-2,31(m, 2H), 2,82(d, J=4.5 Hz, 3H), 3,02-3,20(m, 4H), to 3.35(m, 2H), 3,48(m, 2H), of 4.44(m, J=7.5 Hz, 1H), 7,18(d, J=8.7 Hz, 1H), 7,40(DD, J=2,4, and 8.7 Hz, 1H), of 7.97(d, J=2.1 Hz, 1H), with 8.05 (d, J= 4,8 Hz, 1H), 8,79 (user. 1H), to 10.09 (user. 1H), or 10.60 (user. 1H); 19F NMR (282 MHz, DMSO-d6): d - 163,03; LC/MS: retention time: 10,61 min; purity: 93,48%; MS (mass/charge): 391 (MH+).+
1199N2-[3-Chloro-4-(4-methylpiperazine)phenyl]-N4-cyclohexyl-5-fluoro-2,4-pyrimidinediamine bis-cleaners containing hydrochloride salt1H NMR(DMSO-d6): d 1,17(m, 1H), 1,36(m, 4H), and 1.63(d, 1H), 1,78(m, 2H), to 1.86(m, 2H), and 2.83(d, J=4,8 Hz, 3H), 3,00-3,20(m, 4H), to 3.34(m, 2H), 3,48(m, 2H), a 3.87(m, 1H), 7,16(d, J=8.7 Hz, 1H), was 7.36(DD, J=2,4, and 9.0 Hz, 1H), of 7.96(d, J=2.4 Hz, 1H) 8,03 (d, J= 5,1 Hz, 1H), to 8.41 (user. 1H), of 10.05 (user. 1H), 10,50 (user. 1H); LC/MS: retention time: 14,78 min; purity: 90,99%; MS (mass/charge): 419,39 (MH+).++
1200N4-Cyclopentyl-5-fluoro-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 9,70 min; purity: 89,34%; MS(mass/charge): 385(MH+).+
1201N4-Cyclohexyl-5-fluoro-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 11,34 min; purity: 94,34%; MS(mass/charge): 399,24(MH+).++
1202N4-(3-Cyclopropyl-1H-pyrazole-5-yl)-5-fluoro-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 10,35 min; purity: 96,72%; MS(mass/charge): 423(MH+).++
1203N4-(3,4-Dihydro-2H,4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time is the air traffic management: 10,77 min; purity: 93,79%; MS(mass/charge): 451(MH+).++
12045-fluoro-N4-isopropyl-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: to 3.64 min; purity: 95,29%; MS(mass/charge): 345(MH+).+
1205N2-[3-Chloro-4-(4-methylpiperazine)phenyl]-5-fluoro-N4-isopropyl-2,4-pyrimidinediamineLC/MS: retention time: 5,14 min; purity: 92,47%; MS(mass/charge): 379(MH+).+
12065-fluoro-N4-isopropyl-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 1,99 min; purity: 93,17%; MS(mass/charge): 359(MH+).+-
1207N4-Cyclobutyl-5-fluoro-N2-[4-(4-methylpiperazine)-3-triptoreline]-2,4-pyrimidinediamine LC/MS: retention time: 15,09 min; purity: 94,19%; MS(mass/charge): 425(MH+).+
1208N4-Cyclopentyl-5-fluoro-N2-[4-(4-methylpiperazine)-3-triptoreline]-2,4-pyrimidinediamineLC/MS: retention time: 15,32 min; purity: 92,83%; MS(mass/charge): 439,30(MH+).+
1209N4-Cyclohexyl-5-fluoro-N2-[4-(4-methylpiperazine)-3-triptoreline]-2,4-pyrimidinediamineLC/MS: retention time: 15,74 min; purity: 95,26%; MS(mass/charge): 453(MH+).+
12105-fluoro-N4-isopropyl-N2-[4-(4-methylpiperazine)-3-triptoreline]-2,4-pyrimidinediamineLC/MS: retention time: 7,29 min; purity: 88,24%; MS(mass/charge): 413,05(MH+).+
1211 N4-(3-Cyclopropyl-1H-pyrazole-5-yl)-5-fluoro-N2-[(4-methylpiperazine)-3-triptoreline]-2,4-pyrimidinediamineLC/MS: retention time: 8,27 min; purity: 94,19%; MS(mass/charge): 477(MH+).+
12122-chloro-5-fluoro-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-4-pyrimidinamineLC/MS: retention time: to 9.57 min; purity: 90,78%; MS(mass/charge): 301,19(MH+).-
12132-chloro-N4-(1-ethoxycarbonylpyrimidine-4-yl)-5-fluoro-4-pyrimidinamineLC/MS: retention time: 10,29 min; purity: 94%; MS(mass/charge): 303,04(MH+).-
12145-fluoro-N4-isopropyl-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 4,63 min; purity: 97,16%; MS(mass/charge): 345,41(MH+).-
1215N4-tert-Butyl-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 2,80 min; purity: 97,03%; MS(mass/charge): 359(MH+).-
1216N4-tert-Butyl-5-fluoro-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 7,81 min; purity: 94,56%; MS(mass/charge): 359,23(MH+).-
1217N4-tert-Butyl-N2-[3-chloro-4-(4-methylpiperazine)phenyl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 10,53 min; purity: 93,25%; MS(mass/charge): 393(MH+).+
1218N4-tert-Butyl-5-fluoro-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 4,35 min; purity: 87,23%; MS(mass/charge): 373,26(MH+).+
12195-fluoro-N2-[4-(4-methylpiperazine)phenyl]-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamineLC/MS: retention time: 1,30 min; purity: 95,14%; MS(mass/charge): 456,63(MH+).-
1220N4-Cyclobutyl-5-fluoro-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 9,16 min; purity: 93,00%; MS(mass/charge): 371,26(MH+).+
12215-fluoro-N2-[3-(4-methylpiperazine)phenyl]-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamineLC/MS: retention time: 1,40, 1,71 min; purity: 95%; MS(mass/charge): 456,30(MH+).-
1222N2-[3-Chloro-4-(4-methylpiperazine)phenyl]-5-fluoro-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamineLC/MS: retention time: 1.44MB, 1,74 min; purity: 97%; MS(mass/charge): 40,11(MH+). -
12235-fluoro-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamineLC/MS: retention time: 1,46, 2,03 min; purity: 100%; MS(mass/charge): 470,29(MH+).+
12245-fluoro-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-N2-[3-trifluoromethyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 1,46, 2,70 min; purity: 97%; MS(mass/charge): 524,23(MH+).-
1225N4-(1-Ethoxycarbonylpyrimidine-4-yl)-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 6,13 min; purity: 95,45%; MS(mass/charge): 458(MH+).+
1226N4-(1-Ethoxycarbonylpyrimidine-4-yl)-5-fluoro-N2[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine LC/MS: retention time: 9,94 min; purity: 97%; MS(mass/charge): 458,27(MH+).+
1227N2-[3-Chloro-4-(4-methylpiperazine)phenyl]-N4-(1-ethoxycarbonylpyrimidine-4-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 14,71 min; purity: 98,79%; MS(mass/charge): 492(MH+).+
1228N4-(1-Ethoxycarbonylpyrimidine-4-yl)-5-fluoro-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 9,26 min; purity: 97,16%; MS(mass/charge): 472(MH+).+
1229N4-(1-Ethoxycarbonylpyrimidine-4-yl)-5-fluoro-N2-[4-(4-methylpiperazine)-3-triptoreline]-2,4-pyrimidinediamineLC/MS: retention time: 15,48 min; purity: 97,96%; MS(mass/charge): 526(MH+).+
N4-Cyclobutyl-N2-[2-(4-ethylpiperazine)pyrid-5-yl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 5,52 min; purity: 94,98%; MS(mass/charge): 372(MH+).+
1231N4-Cyclopentyl-N2-[2-(4-ethylpiperazine)pyrid-5-yl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 6,27 min; purity: 90,61%; MS(mass/charge): 386,36(MH+).+
1232N4-Cyclohexyl-N2-[2-(4-ethylpiperazine)pyrid-5-yl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 6,83 min; purity: 97,62%; MS(mass/charge): 400(MH+).+
1233N4-tert-Butyl-5-fluoro-N2-[4-(4-methylpiperazine)-3-triptoreline]-2,4-pyrimidinediamineLC/MS: retention time: shed 15.37 min; purity: 96,00%; MS(mass/charge): 427(MH+).+
1234N2-[2-(4-Ethylpiperazine)pyrid-5-yl]-5-fluoro-N4-isopropyl-2,4-pyrimidinediamineLC/MS: retention time: 1.44MB, of 1.80 min; purity: 96%; MS(mass/charge): 360,28(MH+).+
1235N4-Cyclobutyl-5-fluoro-N2-[3-hydroxymethyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 1,82 min; purity: 90%; MS(mass/charge): 387,14(MH+).-
1236N4-tert-Butyl-N2-[2-(4-ethylpiperazine)pyrid-5-yl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 4,27 min; purity: 100%; MS(mass/charge): 374,18(MH+).-
1237N2-[2-(4-Ethylpiperazine)pyrid-5-yl]-5-fluoro-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamineLC/MS: retention time: 1,27 min; purity: 99,58%; MS(mass/charge): 471,73(MH+).-
1238N4-(1-Ethoxycarbonylpyrimidine-4-yl)-N2-[2-(4-ethylpiperazine)pyrid-5-yl]-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 7,03 min; purity: 94,74%; MS(mass/charge): 473(MH+).-
1239N4-Cyclobutyl-5-fluoro-N2-[2-(4-methylpiperazine)-3-methylpiperid-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 9,65 min; purity: 97,08%; MS(mass/charge): 372,11(MH+).-
1240N4-Cyclopentyl-5-fluoro-N2-[2-(4-methylpiperazine)-3-methylpiperid-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 10,50 min; purity: 91,36%; MS(mass/charge): 385,85(MH+).+
1241N4-Cyclohexyl-5-fluoro-N2-[2-(4-methylpiperazine)-3-methylpiperid-5-yl]-2,4-pyrimidinediamineLC/Prov.: retention time: which 9.22 min; purity: of 93.96%; MS(mass/charge): 400,11(MH+).+
12425-fluoro-N4-isopropyl-N2-[2-(4-methylpiperazine)-3-methylpiperid-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 4,21 min; purity: 91,67%; MS(mass/charge): 360,15(MH+).+
1243N4-Cyclobutyl-5-fluoro-N2-[3-hydroxymethyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine bis-cleaners containing hydrochloride saltLC/MS: retention time: 1,43, of 1.85 min; purity: 94%; MS(mass/charge): 387,05(MH+).+
12445-fluoro-N2-[2-(4-methylpiperazine)-3-methylpiperid-5-yl]-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamineLC/MS: retention time: 7,05 min; purity: 95,56%; MS(mass/charge): 471,26(MH+).-
1245N4-kilobytes-5-fluoro-N2-[2-(4-methylpiperazine)-4-methylpiperid-5-yl]-2,4-pyrimidinediamine LC/MS: retention time: 9,37 min; purity: 92,45%; MS(mass/charge): 371,99(MH+).-
1246N4-Cyclopentyl-5-fluoro-N2-[2-(4-methylpiperazine)-4-methylpiperid-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 10,12 min; purity: 95,69%; MS(mass/charge): 386,09(MH+).-
1247N4-Cyclohexyl-5-fluoro-N2-[2-(4-methylpiperazine)-4-methylpiperid-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 10,35 min; purity: 92,30%; MS(mass/charge): 400,13(MH+).+
12485-fluoro-N4-isopropyl-N2-[2-(4-methylpiperazine)-4-methylpiperid-5-yl]-2,4-pyrimidinediamineLC/MS: retention time: 6,77 min; purity: 84,20%; MS(mass/charge): 359,97(MH+).-
1249 5-fluoro-N2-[2-(4-methylpiperazine)-4-methylpiperid-5-yl]-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamineLC/MS: retention time: 1,48, 2,77 min; purity: 98%; MS(mass/charge): 471,22(MH+).-
12505-fluoro-N4-(1-hydroxymethylcytosine-1-yl)-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 11,16 min; purity: 99,47%; MS(mass/charge): 415,57(MH+).+
1251N4-(5-Amino-1,2,4-triazole-3-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamineLC/MS: purity: 93,2%; MS(mass/charge): 374,52(MH+, 100).+
1252N4-(3-Amino-1,2,4-triazole-5-yl)-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO): d 8,71(d, 1H, J=4.5 Hz), of 7.75(s, 1H), 7,53(s, 2H), 7,21(s, 1H), 6,61-6,74(m, 2H), of 5.83(users, 2H), 2,43(s, 6H); LC/MS: purity: 88,8%; MS(mass/charge): 315,24(MH+, 100). -
1253N4-(5-Amino-1,2,4-triazole-3-yl)-N2-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 92,8%; MS(mass/charge): 351,09(MH+, 100).-
1254N4-(5-Amino-1,2,4-triazole-3-yl)-N2-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 93,2%; MS(mass/charge): 355,23(MH+, 100).-
1255N4-(5-Amino-1,2,4-triazole-3-yl)-5-fluoro-N2-(indazol-6-yl)-2,4-pyrimidinediamineLC/MS: purity: 94,3%; MS(mass/charge): 327,14(MH+, 100).++
1256N4-[(2,3-Dihydro-1,4-benzodioxan-2-yl)methyl]-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO): d to 10.09(users, 1H), 9,12(users, 1H), 8,13(d, 1H, J=5,1 Hz), 7,17(s, 2H), 6,74-6,87(m, 5H), 4,29-4,50(m, 2H), 3,98(DD, 1H, 6,3, 11.4 G is), 3,59-of 3.80(m, 2H), of 2.23(s, 6H); LC/MS: purity: 97.8 per cent; MS(mass/charge): 379,14 (M-, 100).+
1257N4-[(2,3-Dihydro-1,4-benzodioxan-2-yl)methyl]-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamineLC/MS: purity: 97,4%; MS(mass/charge): 438,13 (M-, 100).+
1258N4-[(2,3-Dihydro-1,4-benzodioxan-2-yl)methyl]-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO): d 10,13(s, 1H), 9,05(users, 1H), 8,19(d, 1H, J=4,8 Hz), 6,79-6,86(m, 6H), 6,24(m, 1H), 4,29 figure-4.49(m, 2H), 4,00(DD, 1H, 6,9, and 11.4 Hz), 3,62-with 3.79(m, 8H); LC/MS: purity: 96,7%; MS(mass/charge): 411,10 (M, 100).+
1259N2-(3-Chloro-4-methoxyphenyl)-N4-[(2,3-dihydro-1,4-benzodioxan-2-yl)methyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO): d 10,22(s, 1H), 9,11(users, 1H), 8,12(d, 1H, J=5,1 Hz), of 7.70(d, 1H, J=2.4 Hz), 7,35(DD, 1H, J=2.7, and 9.0 Hz), was 7.08(d, 1H, J=9.0 Hz), is 6.78-6.87 in(m, 4H), 4,28-of 4.49(m, 2H), 3,99(DD, 1H, 6,9, an 11.7 Hz)and 3.59-a-3.84(m, 5H); LC/MS: clean the TA: 96,4%; MS (mass/charge): 415,07 (M-, 100).+
1260N4-[(2,3-Dihydro-1,4-benzodioxan-2-yl)methyl]-5-fluoro-N2-(indazol-6-yl)-2,4-pyrimidinediamineLC/MS: purity: 95,0%; MS(mass/charge): 391,10 (M-, 100).+
1261N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(4-ethoxycarbonylphenyl)-2,4-pyrimidinediamineLC/MS: purity: 100%; MS(mass/charge): 405,09 (M-, 100).-
1262N2-[4-(N-Carboxymethylamino)carbonitril]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 100%; MS(mass/charge): 450,11(M)-
1263(S)-5-fluoro-N2-(4-ethoxycarbonylphenyl)-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO): d 1,74(s, 1H), 9,95(s, 1H), 9,80(s, 1H), 8,18(d, 1H, J=4, 2 Hz), 7,20-7,79(m, 6H), of 6.96(d, 1H, J=9.3 Hz), 4,66(square, 1H, J=6.6 Hz), of 3.78(s, 3H), of 1.45(d, 3H, J=6.6 Hz); LC/MS: purity: 96.8 per cent; MS(mass/charge): 422,12 (M-, 100).+
1264(S)-N2-[4-(N-Carboxymethylamino)carbonitril]-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO): d is 10.75(s, 1H), 9,88(s, 1H), 9,63(m, 1H), 8,19(d, 1H, J=4.5 Hz), 7,19 to 7.75(m, 6H), 6,98(d, 1H, J=8.7 Hz), 4,67(square, 1H, J=6.9 Hz), with 3.89(d, 1H, 5.7 Hz), the 1.44(d, 3H, J=6.9 Hz); LC/MS: purity: 91,2%; MS(mass/charge): 465,21 (M-, 100).-
1265(R)-N2-(4-Aminosulphonylphenyl)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamineLC/MS: purity: 95.5 percent; MS(mass/charge): 407,17 (M-, 100).+
1266(R)-5-fluoro-N2-(4-ethoxycarbonylphenyl)-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO): d a 10.74(s, 1H), 9,95(s, 1H), 9,80(s, 1H), 8,18(d, 1H, J=4, 2 Hz), 7,20 to 7.9(m, 6H), of 6.96(d, 1H, J=9.3 Hz), 4,66(square, 1H, J=6.6 Hz), of 3.78(s, 3H), of 1.45(d, 3H, J=6.6 Hz); LC/MS: purity: 98.5 per cent; MS(mass/charge): 422,17 (M-, 100).+
1267(R)-N2-[4-(N-Carboxymethylamino)carbonitril]-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO): d is 10.75(s, 1H), 9,88(s, 1H), 9,63(m, 1H), 8,19(d, 1H, J=4.5 Hz), 7,19 to 7.75(m, 6H), 6,98(d, 1H, J=8.7 Hz), 4,67(square, 1H, J=6.9 Hz), with 3.89(d, 1H, 5.7 Hz), the 1.44(d, 3H, J=6.9 Hz); LC/MS: purity: 87,5%; MS(mass/charge): 465,21 (M-, 100).-
1268N2,N4-Bis[4-(N-tert-butoxycarbonylamino)methylindenyl]-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 100%; MS(mass/charge): 537,34 (M-, 100).+
1269N2,N4-Bis(4-aminomethylphenol)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO): d 9,25(users, 1H), which is 9.09(users, 1H), with 8.05(d, 1H, J=2.4 Hz), 7,69(d, 2H, J=8.7 Hz), 7,56(d, 2H, J=8.7 Hz),? 7.04 baby mortality-7,40(m, 4H), to 3.67(s, 3H), 3,61(s, 3H), 3,35(users, 4H); LC/MS: purity: 95.5 percent; MS(mass/charge): 37,18 (M, 100)++++
1270N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[4-(N-methoxycarbonylmethylene)carbonitril]-2,4-pyrimidinediamine1H NMR(DMSO): d of 10.21(s, 2H), with 8.33(m, 1H), with 8.33(d, 1H, J=4.5 Hz), 8,10(d, 1H, J=2.4 Hz), to 7.59-7,83(m, 6H), 3,99(m, 2H), the 3.65(s, 3H); LC/MS: purity: 100%; MS(mass/charge): 462,11 (M-, 100).+
1271(S)-5-fluoro-N2-[4-(N-methoxycarbonylmethylene)carbonitril]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO): d 10,77(s, 1H), to 9.93(users, 1H), 8,77(m, 1H), to 8.20(d, 1H, J=4.5 Hz), 7,21 to 7.75(m, 6H), 6,97(d, 1H, J=8,4 Hz), 4,66(square, 1H, J=6.6 Hz), of 3.97(m, 2H), to 3.64(s, 3H), of 1.44(d, 3H, J=6.6 Hz); LC/MS: purity: 96,7%; MS(mass/charge): 481,16(MH+,100).+-
1272(R)-5-fluoro-N2-[4-(N-methoxycarbonylmethylene)carbonitril]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO): d 10,77(s, 1H), to 9.93(users, 1H), 8,77(m, 1H), to 8.20(d, 1H, J=4.5 Hz), 7,217,75(m, 6H), 6,97(d, 1H, J=8,4 Hz), 4,66(square, 1H, J=6.6 Hz), of 3.97(m, 2H), to 3.64(s, 3H), of 1.44(d, 3H, J=6.6 Hz); LC/MS: purity: 100%; MS(mass/charge): 481,39(MH+, 100).+-
1273N2,N4-Bis[3-(N-tert-butoxycarbonylamino)methylindenyl]-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO): d 9,43(s, 1H), which 9.22(s, 1H), remaining 9.08(d, 1H, J=3.6 Hz), 7.24 to 7,72(m, 7H), to 7.15(t, 1H, J=7.8 Hz), 6,94(d, 1H, J=7.5 Hz), 6,78(d, 1H, J=7.5 Hz), 4,08(m, 4H), of 1.39(s, 18H); LC/MS: purity: 95,8%; MS(mass/charge): 537,16 (M-, 100).+
1274N2,N4-Bis(3-aminomethylphenol)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO): d 9,24(s, 1H), 8,35(s, 1H), 8,01-8,07(m, 2H), 6.73 x-7,71(m, 7H), of 3.69(s, 2H), 3,61(s, 2H); LC/MS: purity: 100%; MS(mass/charge): 337,21 (M-, 100).++
1275N2-[3-(N-tert-Butoxycarbonylamino)methylindenyl]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: purity: 93.5 per cent; MS(mass/charge): 476,19 (M-, 100).++/td>
1276(S)-N2-[3-(N-tert-Butoxycarbonylamino)methylindenyl]-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO): d 10,61(s, 1H), of 9.30(s, 1H), 9,04(s, 1H), 8,03(d, 1H, J=3,9 Hz), 7,22-rate of 7.54(m, 5H), 7,10(t, 1H, J=7.5 Hz), 6,92(d, 1H, J=7.5 Hz), with 4.64(square, 1H, J=6,6 Hz)to 4.01(m, 2H), of 1.44(d, 3H, J=6,6 Hz)of 1.39(s, 9H); LC/MS: purity: 95,1%; MS (mass/charge): 493,28 (M-, 100).++
1277(R)-N2-[3-(N-tert-Butoxycarbonylamino)methylindenyl]-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)1H NMR(DMSO): d 10,61(s, 1H), of 9.30(s, 1H), 9,04(s, 1H), 8,03(d, 1H, J=3,9 Hz), 7,22-rate of 7.54(m, 5H), 7,10(t, 1H, J=7.5 Hz), 6,92(d, 1H, J=7.5 Hz), with 4.64(square, 1H, J=6,6 Hz)to 4.01(m, 2H), of 1.44(d, 3H, J=6,6 Hz)of 1.39(s, 9H); LC/MS: purity: 92,2%; MS (mass/charge): 493,28 (M-, 100).++
1278N2-(3-Aminomethylphenol)-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO): d 9,60(users, 1H), 9,31(s, 1H), 8,16(d, 1H, J=3.6 Hz), to 8.12(d, 1H, J=2.7 Hz), for 6.81-7,88(m, 6H), 3,70(s, 2H); LC/MS: purity: 96.4 per cent; MS(mass/ZAR is d): 376,11 (M, 100).++
1279(S)-N2-(3-Aminomethylphenol)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO): d of 9.30(s, 1H), remaining 9.08(s, 1H), with 8.05(m, 1H), 6,76-of 7.60(m, 8H), 4,63(square, 1H, J=6,9 Hz)to 3.64(s, 2H), USD 1.43(d, 3H, J=6.9 Hz); LC/MS: purity: 100%; MS(mass/charge): 393,20 (M-, 100).++
1280(R)-N2-(3-Aminomethylphenol)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl-2,4-pyrimidinediamine1H NMR(DMSO): d of 9.30(s, 1H), remaining 9.08(s, 1H), with 8.05(m, 1H), 6,76-of 7.60(m, 8H), 4,63(square, 1H, J=6,9 Hz)to 3.64(s, 2H), USD 1.43(d, 3H, J=6.9 Hz); LC/MS: purity: 98.5 per cent; MS(mass/charge): 393,20 (M-, 100).++
1281N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO): d 10,69(s, 1H), 10,18(users, 1H), of 8.25(d, 1H, J=4.5 Hz), 8,12-8,17(m, 2H), 7,73(d, 1H, J=8.1 Hz), a 7.62(d, 1H, J=7.5 Hz), 7,21-7,39(m, 4H), 6,76(d, 1H, J=8,4 Hz)to 1.38(s, 6H); LC/MS: purity: 100%; MS(mass/charge): 445,14 (M, 100).++-
1282(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO): d 10,69(s, 1H), 9,98(users, 2H), by 8.22(d, 1H, J=2.4 Hz), 8,16(m, 1H), 7,21 to 7.75(m, 6H), is 6.78(d, 1H, J=8,4 Hz), 4,62(square, 1H, J=6,9 Hz)of 1.42(d, 3H, J=6.9 Hz); LC/MS: purity: 97,3%; MS(mass/charge): 431,15 (M-, 100).++-
1283(R)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO): d 10,69(s, 1H), 9,98(users, 2H), by 8.22(d, 1H, J=2.4 Hz), 8,16(m, 1H), 7,21 to 7.75(m, 6H), is 6.78(d, 1H, J=8,4 Hz), 4,62(square, 1H, J=6,9 Hz)of 1.42(d, 3H, J=6.9 Hz); LC/MS: purity: 94,9%; MS(mass/charge): 431,15 (M-, 100).++-
1284N4-(2,2-Debtor-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO): d a 12.05(s, 1H), of 10.05(s, 1H), 9,95(s, 1H), 8,27(m, 1H), of 8.25(d, 1H, J=4.5 Hz), 8,14(s, 1H), 7,32 to 7.75(m, 6H), 7,13(d, 1H, J=9.0 Hz); LC/MS: purity:98,0%; MS(mass/charge): 453,12 (M-, 100).++-
1285N4-(4-Amino-3,4-dihydro-2H-1-benzopyran-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamineLC/MS: purity: 87,8%; MS(mass/charge): 417,18 (M-, 100).++-
1286N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(N-methoxycarbonylmethylene)carbonitril]-2,4-pyrimidinediamine1H NMR(DMSO): d 10,71(s, 1H), to 9.91(users, 1H), 8,73(m, 1H), 1,19(d, 1H, J =4.5 Hz), 7,19-7,74(m, 6H), 6,94(d, 1H, J=8,4 Hz), of 3.97(m, 2H), to 3.64(s, 3H), of 1.38(s, 6H); LC/MS: purity: 97,5%; MS(mass/charge): 493,22 (M-, 100).++-+
1287N4-(4-N-tert-Butoxycarbonylamino-3,4-dihydro-2H-1-benzopyran-6-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamineLC/MS: purity: 89,3%; MS(mass/charge): 517,26 (M-, 100).+-
1288N4-(4-N-tert-Butoxycarbonylamino-3,4-dihydro-2H-1-benzopyran-6-yl)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamineLC/MS: purity: 96,6%; MS(mass/charge): 516,90 (M-, 100).+++
1289N4-(4-N-tert-Butoxycarbonylamino-3,4-dihydro-2H-1-benzopyran-6-yl)-5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamineLC/MS: purity: 87,2%; MS(mass/charge): 517,54 (M-, 100).++
12905-fluoro-N4-(4-hydroxy-3,4-dihydro-2H-1-benzopyran-6-yl)-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamineLC/MS: purity: 100%; MS(mass/charge): 518,16
(M-, 100).
++-
12915-fluoro-N4-(4-hydroxy-3,4-dihydro-2H-1-benzopyran-6-yl)-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO): d the 10.40(s, 1H), of 10.25(s, 1H), compared to 8.26(d, 1H, J=4,8 Hz), 8,15(s, 1H), 7,65-7,83(m, 4H), to 7.50(d, 1H, J=2.7 Hz), 7,40(DD, 1H, J 2.7, and an 8.4 Hz), 7,32(s, 1H), for 6.81(d, 1, J=8.7 Hz), 4,59(t, 1H, J=5,1 Hz), 4,20-4,24(m, 2H), 1.70 to 2, 10 (m, 2H); LC/MS: purity: 94,0%; MS (mass/charge): 418,03 (M-, 100).++-
1292(R,S)-N4-[4-Amino-3,4-dihydro-2H-1-benzopyran-6-yl]-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d a 9.25(s, 1H), 9,19(s, 1H), 8,35(s, 1H), with 8.05(d, J=3.6 Hz, 1H), 7,99(m, 1H), 7,20-7,63(m, 5H), 6,62(d, J=8.7 Hz, 1H), 3,86-4,20(m, 3H), 1,75-2,0(m, 2H); LC/MS: purity: 91,8%; MS(mass/charge): 419,3(MH+).++-
1293(R,S)-N4-[4-Amino-3,4-dihydro-2H-1-benzopyran-6-yl]-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamineLC/MS: purity: 98,0%; MS(mass/charge): 419,2(MH+).+
1294(R,S)-N4-[4-Amino-3,4-dihydro-2H-1-benzopyran-6-yl]-5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamineLC/MS: purity: 93.5 per cent; MS(mass/charge): 419,3(MH+).+
1295N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-[N-(N-methylamino)carbonylmethyl]aminocarbonyl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d of 10.73(s, 1H), becomes 9.97(s, 1H), 9,87(s, 1H), 8,53(m, 1H), 8,19(d, J=4,2 Hz, 1H), 7,66-7,83(m, 5H), 7.24 to 7,27(m, 2H), 6,94(d, J=8,4 Hz, 1H), 3,78(d, J=5.7 Hz, 2H), 2,58(d, J=4.5 Hz, 3H), of 1.41(s, 6H); purity of 98.2%; MS (mass/charge): 494,3 (MH+).++-
1296(S)-5-fluoro-N2-[4-[N-(N-methylamino)carbonylmethyl]aminocarbonyl]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,85(s, 1H), of 10.21(s, 1H), 9,98(s, 1H), 8,58(m, 1H), they were 8.22(d, J=4.5 Hz, 1H), 7.68 per-7,79(m, 6H), 7,43(m, 1H), 7.23 percent(m, 1H), 6,95(d, J=9.0 Hz, 1H)and 4.65(sq, J=6.3 Hz, 1H), 3,79(m, 2H), 2,58(d, J=4.5 Hz, 3H), USD 1.43(d, J=6.3 Hz, 3H); LC/MS: purity: 100%; MS (mass/charge): 480,3(MH+).++-
1297N4-(2,2-Debtor-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-[N-(N-methylamino)carbonylmethyl]aminocarbonyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 12,11(s, 1H), 9,87(s, 1H), 9,81(s, 1H), 8,53(m, 1H), to 8.20(d, J=3,9 Hz, 1H), to 7.67 for 7.78(m, 6H), 7,54(DD, J=2,4, and 8.7 Hz, 1H), 7,29(d, J=9.0 Hz, 1H, with 3.79(d, J=6.0 Hz, 2H), 2,58(d, J=4,2 Hz, 1H); LC/MS: purity: 97.8 per cent; MS (mass/charge): 502,3(MH+).+-
1298(R,S)-N4-[4-(N-tert-Butoxycarbonyl)amino-3,4-dihydro-2H-1-benzopyran-6-yl]-5-fluoro-N2-[4-[N-(N-methylamino)carbonylmethyl]aminocarbonyl]-2,4-pyrimidinediamineLC/MS: purity 97%; MS(mass/charge): 566,4(MH+).+-
1299(R,S)-N4-[4-Amino-3,4-dihydro-2H-1-benzopyran-6-yl]-5-fluoro-N2-[4-[N-(N-methylamino)carbonylmethyl]aminocarbonyl]-2,4-pyrimidinediamineLC/MS: purity: 93.5 per cent; MS(mass/charge): 466,3(MH+).++-+
1300N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[4-[N-(N-methylamino)carbonylmethyl]aminocarbonyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,84(s, 1H), 9,81(s, 1H), 8,54(m, 1H), 8,24(d, J=3,9 Hz, 1H), 8,10(d, J=2.4 Hz, 1H), 7.68 per-7,81(m, 6H), 7,56(d, J=9.0 Hz, 1H), 3,79(d, J=6.0 Hz, 2H), 2,58(d, J=3,9 Hz, 3H); LC/MS: purity: 100%; MS(mass/charge): 463,2(MH+). ++-
1301N4-(3,4-Dichlorophenyl)-5-fluoro-N4-methyl-N2-[4-[N-(N-methylamino)carbonylmethyl]aminocarbonyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.75(s, 1H), and 8.50(m, 1H), 8,12(d, J=4,8 Hz, 1H), 7,63-7,79(m, 7H), 7,34(DD, J=2,4, 9.6 Hz, 1H), 3,78(d, J=4,8 Hz, 2H), to 3.09(s, 3H), 2,58(d, J=4.5 Hz, 3H); LC/MS: purity: 94,1%; MS(the mass/charge): 477,2(MH+).++-
1302N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-[N-(2-methoxycarbonylethyl)aminocarbonyl]phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,71(s, 1H), to 9.93(users, 2H), 8,32(m, 1H), 8,19(d, J=4,8 Hz, 1H), to 7.61-of 7.69(m, 4H), 7,22-7,25(m, 2H), 6,94(d, J=6,93 Hz, 1H), 3,60(s, 3H), 3,44(sq, J=6,9 Hz, 2H), 2.57 m(t, J=6,9 Hz, 2H), 1,41(s, 6H); LC/MS: purity: 97,5%; MS (mass/charge): 509,3(MH+).+++
1303(S)-5-fluoro-N2-[4-[N-(2-methoxycarbonylethyl)aminocarbonyl]phenyl]-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,83(s, 1H), 10,32(s, 1H), 10,13(s, 1H), 8,39(m, 1H), 8,25(d, J=4,8 Hz, 1H), 7,62-772(m, 4H), 7,35(s, 1H), 7,21(DD, J=2,4, and 8.7 Hz, 1H), of 6.96(d, J=8.7 Hz, 1H), 4,66(sq, J=6,9 Hz, 1H)and 3.59(s, 3H), 3.43 points(m, 2H), 2.57 m (t, J=7,6 Hz, 2H), USD 1.43 (d, J=6.9 Hz, 3H); LC/MS: purity: 90,1%; MS (mass/charge): 495,3 (MH+).++-
1304N4-(2,2-Debtor-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-[N-(2-methoxycarbonylethyl)aminocarbonyl]phenyl]-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 12,15(s, 1H), 9,85(m, 2H), 8,31(m, 1H), to 8.20(d, J=4,2 Hz, 1H), 7,70 for 7.78(m, 5H), 7,50(d, J=9.6 Hz, 1H), 7,27(d, J=9,90 Hz, 1H)and 3.59(s, 3H), 3,42(m, 2H), has 2.56(t, J=6.9 Hz, 2H); LC/MS: purity: 88,5%; MS(mass/charge): 517,3(MH+).++-
1305N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[4-[N-(2-methoxycarbonylethyl)aminocarbonyl]phenyl]-2,4-pyrimidinediamine1H NMR (DMSO-d6): d 9,82(s, 1H), made up 9.77(s, 1H), at 8.36(m, 1H), 8,24(d, J=3,9 Hz, 1H), 8,11(d, J=2.4 Hz, 1H), 7,65-7,79(m, 5H), 7,56(d, J=8.7 Hz, 1H), 3,60(s, 3H), 3,47(sq, J=6,6 Hz, 2H), 2.57 m(t, J=6,6 Hz, 1H); purity 90,9%; MS(mass/charge): 478,2(MH+).+++
1306N4-(3,4-Dichlorophenyl)-5-fluoro-N2-[4-[N-(2-methoxycarbonylethyl)and enacarbil]phenyl]-N4-methyl-2,4-pyrimidinediamine 1H NMR(DMSO-d6): d 9,94(s, 1H), to 8.41(m, 1H), 8,16(d, J=5.7 Hz, 1H), of 7.64 to 7.75(m, 6H), was 7.36(DD, J=2,4, and 8.7 Hz, 1H)and 3.59(s, 3H), 3,50(s, 3H), of 3.45(m, 2H), 2.57 m(t, J=7,6 Hz, 2H); LC/MS: purity: 88,5%; MS(mass/charge): 492,2(MH+).++-
1307N2-[4-[1-(tert-Butoxycarbonylamino)methylanthranilate]were]-N4-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 10,59(s, 1H), 9,29(s, 1H), 9,01(s, 1H), 8,12(m, 1H), 8,03(d, J=3.6 Hz, 1H), 7,56(d, J=9.0 Hz, 2H), 7,27(DD, J=2.1 a, and 8.4 Hz, 1H), 7,21(d, J=2.4 Hz, 1H), 7,05(d, J=8.7 Hz, 2H), 6.90 to(d, J=9.0 Hz, 2H), 4.16 the(d, J=5.4 Hz, 2H), 3,54 (d, J=5.4 Hz, 2H), 1.39 in (c, 6H), 1,38 (c, 9H); LC/MS: purity: 90,1%; MS (mass/charge): 566,5 (MH+).+++
1308(S)-N2-[4-[1-(tert-Butoxycarbonylamino)methylanthranilate]were]-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine1H NMR(DMSO-d6): d as 10.63(s, 1H), 9,29(s, 1H), 9,00(s, 1H), 8,13(m, 1H), 8,03(d, J=3.6 Hz, 1H), 7.29 trend-EUR 7.57(m, 3H), 7,21(d, J=2.1 Hz, 1H), 7,05(d, J=9.0 Hz, 2H), make 6.90(d, J=8,4 Hz, 2H)and 4.65(sq, J=7.5 Hz, 1H), 4.16 the(d, J=5.7 Hz, 2H), 3,53 (d, J=6.3 Hz, 2H), USD 1.43 (d, J=6.6 Hz, 3H), 1,38 (c, 9H); LC/MS: purity: 90,1%; MS (mass/charge): 552,4 (MH+). +++
1309N2-[4-[1-(tert-Butoxycarbonylamino)methylanthranilate]were]-N4-(2,2-debtor-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,52(s, 1H), remaining 9.08(s, 1H), 8,13(m, 1H), of 8.09(d, J=3.3 Hz, 1H), 7,46 to 7.62(m, 4H), of 7.23(d, J=8.7 Hz, 2H), 7,07(d, J=8,4 Hz, 2H), 6,92(m, 1H), 4,18(d, J=5.7 Hz, 2H), 3,54(d, J=5.7 Hz, 2H), of 1.37(s, 9H); LC/MS: purity: 93.1%of; MS (mass/charge): 574,4 (MH+).++-
1310N2-[4-[1-(tert-Butoxycarbonylamino)methylanthranilate]were]-N4-(3,4-dichlorophenyl)-5-fluoro-2,4-pyrimidinediamine1H NMR(DMSO-d6): d of 9.56(s, 1H), 9.28 are(s, 1H), 8,12-8,17(m, 3H), 7,51-7,81(m, 4H), 7,14(d, J=8.7 Hz, 2H), 6,93(m, 1H), 4,20(d, J=6.3 Hz, 2H), 3,54(d, J=6.6 Hz, 2H), to 1.38(s, 9H); LC/MS: purity: 94,1%; MS(mass/charge): 535,3(MH+).+++
1311N2-[4-[1-(tert-Butoxycarbonylamino)methylanthranilate]were]-N4-(3,4-dichlorophenyl)-5-fluoro-N4-methyl-2,4-pyrimidinediamine1H NMR(DMSO-d6): d 9,31(s, 1H), 8,15(m, 1H), 8,04(d, J=5.4 Hz, 1H), ,55-7,66(m, 4H), 7,30(m, 1H), was 7.08(d, J=8.7 Hz, 2H), 6,94(m, 1H), 4,18(d, J=6.3 Hz, 2H), 3,54(d, J=6.3 Hz, 2H), 3.46 in(s, 3H), of 1.38(s, 9H); LC/MS: purity: 90,1%; MS (mass/charge): 549,3 (MH+).+-
1312N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-[4-[N-(2-methoxycarbonylethyl)aminocarbonyl]phenyl]-2,4-pyrimidinediamineLC/MS: retention time: 3,67 min(9 min method); purity: 95.3 per cent; MS(mass/charge): 496,3(MH+).++
1313N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(4-ethoxycarbonylphenyl)-2,4-pyrimidinediamineLC/MS: retention time: 4,45 min(9 min method); purity: 97,3%; MS(mass/charge): RUR 439,3(MH+).+
1314N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3-methoxycarbonylmethyl-2-yl)-2,4-pyrimidinediamineLC/MS: retention time: 4,00 min(9 min method); purity: 95,1%; MS(mass/charge): 440,4(MH+).+
1315N2-(4-Aminosulphonylphenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 3.28 minutes(9 minutes method); purity: 98.1 per cent; MS(mass/charge): 424,3(MH+).+
1316N2-(2-Aminocarbonylmethyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 3,98 min(9 min method); purity: 90,1%; MS(mass/charge): 424,5(MH+).+-
1317N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-(indazol-6-yl)-2,4-pyrimidinediamine salt methanesulfonic acidLC/MS: retention time: 8,50 min(20 min method); purity: 98,8%; MS(mass/charge): 420,1(MH+).
1318N4-(2,2-Debtor-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine salt methanesulfonic acid LC/MS: retention time: RS 9.69 min(20 min method); purity: 98.4 per cent; MS(mass/charge): 475,3(MH+).
1319N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 3,17 min(7 min method); purity: 97,5%; MS(mass/charge): 460,3(MH+).+
1320N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(4-[2-[N,N-diethylamino]utilization.carbons]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,64 min(7 min method); purity: 100%; MS(mass/charge): 487,3(MH+).++
1321N2-(4-Aminosulphonylphenyl)-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 2,86 min(7 min method); purity: 100%; MS(mass/charge): 488,3(MH+).+ +
1322N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(4-ethoxycarbonylphenyl)-2,4-pyrimidinediamineLC/MS: retention time: as 4.02 min(7 min method); purity: 98.4 per cent; MS(mass/charge): 403,3(MH+).+
1323N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(4-[N-tert-butoxycarbonylmethylene]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 3,83 min(7 min method); purity: 92,3%; MS(mass/charge): 474,3(MH+).+
1324N2-(4-Aminomethylphenol)-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 2,53 min(7 min method); purity: 96,6%; MS(mass/charge): 374,2(MH+).+
1325N4-(3-Chloro-4-methoxyphenyl)-5-fluoro-N2-(4-[N-[N-methyl]aminocarbonylmethyl]aminocarbonyl]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,in(7 min method); purity: 100%; MS(mass/charge): 459,3(MH+).+
13262-Chloro-5-fluoro-N4-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-4-pyrimidinamineLC/MS: retention time: 2,79 min(7 min method); purity: 100%; MS(mass/charge): 339,2(MH+).-
1327N4-[4-Aminocarbonylmethyl]-2-chloro-5-fluoro-4-pyrimidinamineLC/MS: retention time: 2.40 a min(7 min method); purity: 100%; MS(mass/charge): 267,1(MH+).-
13285-fluoro-N2-(3-hydroxyphenyl)-N4-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,44 min(7 min method); purity: 94,9%; MS(mass/charge): 412,3(MH+).+
1329N2-(3,5-Dichloro-4-hydroxide who yl)-5-fluoro-N4-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-2,4-pyrimidinediamine LC/MS: retention time: 9,92 min(20 min method); purity: 95,0%; MS(mass/charge): 482,0(MH+).+
1330N2-(3-Chloro-4-methoxyphenyl)-5-fluoro-N4-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 3,13 min(7 min method); purity: 95% MS(mass/charge): 460,3(MH+).+++
1331N2-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N4-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,80 min(7 min method); purity: 92,2%; MS(mass/charge): 495,3(MH+).++
13325-fluoro-N2,N4-bis(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,77 min(7 min method); purity: 100%; MS(mass/charge): 511,4(MH+).++
1333N2-(4-Aminosulphonylphenyl)-5-fluoro-N4-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,48 min(7 min method); purity: 97,6%; MS(mass/charge): RUR 439,3(MH+).--
1334N4-(4-Aminosulphonylphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,10 min(7 min method); purity: 100%; MS(mass/charge): 340,2(MH+).++
1335N4-(4-Aminosulphonylphenyl)-N2-(3,5-dichloro-4-hydroxyphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 8,72 min(20 min method); purity: 93,0%; MS(mass/charge): 410,0(MH+).++
1336N4-(4-Aminosulphonylphenyl)-N2-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: ,79 min(7 min method); purity: 100%; MS(mass/charge): 388,3(MH+).++
1337N4-(4-Aminosulphonylphenyl)-N2-(2,2-dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 2,50 min(7 min method); purity: 100%; MS(mass/charge): 423,3(MH+).+++
1338N4-(Aminocarbonylmethyl)-5-fluoro-N2-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,52 min(7 min method); purity: 94,4%; MS(mass/charge): RUR 439,3(MH+).++
1339N2,N4-Bis(4-aminosulphonylphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: of 2.26 min(7 min method); purity: 100%; MS(mass/charge): 367,3(MH+).--
1340N4-(2,2-is imethyl-3-oxo-4H-N4-oxo-5-pyrido[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine LC/MS: retention time: 3,48 min(7 min method); purity: 97,4%; MS(mass/charge): 487,3(MH+).++
1341N2-(4-Aminosulphonylphenyl)-5-fluoro-N4-(4-[3-methyl-1,2,4-oxadiazol-5-yl]methylenedioxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,72 min(7 min method); purity: 95,8%; MS(mass/charge): 436,3(MH+).+++
13425-fluoro-N2-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-N4-(4-[3-methyl-1,2,4-oxadiazol-5-yl]methylenedioxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,99 min(7 min method); purity: 95,1%; MS(mass/charge): 508,4(MH+).++
1343N2-(4-[2-[N,N-Diethylamino]utilization.carbons]phenyl)-5-fluoro-N4-(4-[3-methyl-1,2,4-oxadiazol-5-yl]methylenedioxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,58 min(7 min method); purity: 97.8 per cent; MS(mass/charge): 535,4(MH+). +++
1344N2-(3,5-Dichloro-4-hydroxyphenyl)-5-fluoro-N4-(4-[3-methyl-1,2,4-oxadiazol-5-yl]methylenedioxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time: 3,33 min(7 min method); purity: 95,0%; MS(mass/charge): 477,2(MH+).+-+
1345N2-(3-Chloro-5-methoxyphenyl)-5-fluoro-N4-(4-[3-methyl-1,2,4-oxadiazol-5-yl]methylenedioxyphenyl)-2,4-pyrimidinediamineLC/MS: retention time: 3,35 min(7 min method); purity: 96.4 per cent; MS(mass/charge): 457,3(MH+).-+
1346N2-(4-Aminosulphonylphenyl)-N4-(3,4-dichlorophenyl)-5-fluoro-N4-methyl-2,4-pyrimidinediamineLC/MS: retention time: 3,86 min(7 min method); purity: 100%; MS(mass/charge): 406,2(MH+).+
1347N2-(4-[2-[N,N-Diethylamino]utilization.carbons]f the Nile)-N4-(3,4-dichlorophenyl)-5-fluoro-N4-methyl-2,4-pyrimidinediamine LC/MS: retention time: 3,31 min(7 min method); purity: 100%; MS(mass/charge): 505,3(MH+).+
1348N4-(3,4-Dichlorophenyl)-5-fluoro-N2-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-N4-methyl-2,4-pyrimidinediamineLC/MS: retention time: 4,16 min(7 min method); purity: 95,8%; MS(mass/charge): of 480.2(MH+).+
1349N2-(4-Aminosulphonylphenyl)-N4-(cyclopentyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: of 2.26 min(7 min method); purity: 100%; MS(mass/charge): 316,3(MH+).-
1350N4-(Cyclopentyl)-N2-(4-[2-(N,N-diethylamino]utilization.carbons)phenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 2,09 min(7 min method); purity: 97,3%; MS(mass/charge): 415,4(MH+).-+
1351N4-(Cyclopentyl)-5-fluoro-N2-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 2,62 min(7 min method); purity: 100%; MS(mass/charge): 388,3(MH+).++
1352N2-(4-Aminosulphonylphenyl)-N4-(4-chloro-3-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 3,13 min(7 min method); purity: 96.4 per cent; MS(mass/charge): 388,3(MH+).+
1353N2-(4-Aminocarbonyl-3-chlorophenyl)-N4-(3-chloro-4-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 2,91 min(7 min method); purity: 89,5%; MS(mass/charge): 422,2(MH+).++
1354N2-(4-Aminocarbonyl-3-chlorophenyl)-N4-(4-chloro-3-methoxyphenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 3,14 min(7 min method); pure is a: 95,0%; MS(mass/charge): 422,2(MH+).++
1355N4-(4-Chloro-3-methoxyphenyl)-N2-(4-[2-[N,N-diethylamino]utilization.carbons]phenyl)-5-fluoro-2,4-pyrimidinediamineLC/MS: retention time: 2,80 min(7 min method); purity: 95.6%of; MS(mass/charge): 487,4(MH+).++
1356N4-(4-Chloro-3-methoxyphenyl)-5-fluoro-N2-(4-[N-[methoxycarbonylmethylene]aminocarbonyl]phenyl)-2,4-pyrimidinediamineLC/MS: retention time: 3,45 min(7 min method); purity: 94,6%; MS(mass/charge): 460,3(MH+).++
1357N2-(4-Aminosulphonylphenyl)-5-fluoro-N4-phenyl-2,4-pyrimidinediamineLC/MS: retention time: 2,58 min(7 min method); purity: 100%; MS(mass/charge): 424,3(MH+).++
13585-fluoro-N2-(3-GI is roxiprin)-N4-(4-[3-methyl-1,2,4-oxadiazol-5-yl]methylenedioxyphenyl)-2,4-pyrimidinediamine cleaners containing hydrochloride salt LC/MS: retention time: 2,72 min(7 min method); purity: 89,9%; MS(mass/charge): 409,3(MH+).
1NMR - nuclear magnetic resonance;
2LC - liquid chromatography;
3MS - mass spectrometry

7.5 Effectiveness of the compounds in the treatment of autoimmunity

Assessment of the effectiveness ofin vivoindividual compounds are 2,4-pyridinediamine in relation to autoimmune diseases was obtained on the example of reversible passive reaction artusa, which is a model of severe tissue injury mediated by a pair of antigen-antibody, as well as in several models of diseases associated with autoimmunity and inflammation. These models are similar in the sense that the antibody to a specific antigen mediates inflammatory disease caused by immune complex (IC)and associated tissue destruction. The IC deposition in certain anatomical sites (Central nervous system (CNS) in the case of experimental autoimmune encephalomyelitis (EAE) and synovial membrane in the case of collagen-induced arthritis (CIA)) leads to activation of cells expressing surface receptors FcγR and FcεR, the advantage is significant mastocyte, macrophages and neutrophils, which leads to cytokine secretion and chemotaxis of neutrophils. Activation of the inflammatory response is responsible for the reaction of nerve endings in the forward direction to flow, including edema, hemorrhage, infiltration of neutrophils, as well as the secretion of proinflammatory mediators. In the case of autoimmune disorders, the consequences of these events provoked IC, it is difficult to establish; however, many researchers have shown that inhibition of signaling pathways FcγR receptors in these animal models has led to a significant weakening of disease development and severity of its course.

7.5.1 the effectiveness of the compounds in the reaction artusa in mice

Efficiency (in vivo) compounds 810, 944, 994 and 1007 for inhibiting the inflammatory cascade triggered IC, was demonstrated by reverse passive reaction artusa in mice (reaction RPA).

7.5.1.1 Model

Acute inflammatory tissue injury mediated by immune complex (IC)is a part of many different autoimmune diseases, including vasculitis syndrome, serum sickness, systemic lupus erythematous (SLE), rheumatoid arthritis, syndrome? and glomerulonephritis. Classic experimental model of tissue damage mediated IC is reversible passive is I reaction artusa. The model of this reaction is a convenientin vivomethod of studying localized inflammation caused by immune complexes, in the absence of systemic effects. Subcutaneous injection of antibodies (Ab)specific for albumin chicken egg, (anti-OVA immunoglobulin IgG rabbit), followed by an intravenous infusion (IV) antigens (Ag), namely, albumin egg (egg albumin), OVA), causes oxaloacetate the deposition of immune complexes and immediate inflammatory reaction characterized by edema, infiltration of neutrophils and bleeding at the injection sites. Some aspects of the model RPA reactions in mice similar to the inflammatory response of patients suffering from rheumatoid arthritis, SLE and glomerulonephritis.

7.5.1.2 the study Protocol

In this model, the compounds are introduced at certain points in time before the introduction of antibodies and antigens. A solution of anti-OVA immune globulin rabbit IgG (50 μg in 25 μl/mouse) subcutaneously, followed by intravenous injection of albumin obtained from chicken eggs (20 mg/kg of body weight), in a solution containing 1% blue dye Evans. The degree of edema and hemorrhage are measured in the skin of the back of C57BL/6 mice using blue dye Evans as an indicator of local tissue damage. As the control is about substances used purified polyclonal rabbit immunoglobulin IgG.

The period of time between the introduction of the investigated compounds and complex antibody/antigen depends on the pharmacokinetic (PK) properties of each individual connection. Four hours after induction of the reaction artusa mice were euthanized and took a sample of tissue to assess edema. This model allows to trace the in vivo activity of most inhibitors.

7.5.1.3 Results

All tested compounds were administered orally by the way.

The drug 994 with the introduction in the amount of 100 mg/kg for 90 minutes prior to the introduction of antibody/antigen when tested on mice C57Bl6 showed the dependence of the inhibition of the formation of swelling of the injected dose (75%).

Connection 1007 and 810 showed effective inhibition of edema development by 89.4% 81,3%, respectively, with the introduction in the amount of 1.0 mg/kg 30 minutes before exposure to the antibody/antigen.

Connection 1007 showed 64.3 per cent, to 78.7%, 98,1% and 99.8%of inhibition of the formation of edema at a dose of 0.1 mg/kg, 0.5 mg/kg, 1.0 mg/kg and 5 mg/kg when taken 30 minutes respectively. The results of the test compounds shown in table 2.

Table 2
The aggregated results by reverse passive reaction artusa (RPA) in mice
% inhibition of control fillerSatellite: during introductionShutter speed = time sedation + 4 hoursPotency in vitro (CHMC IgE)
Name
connection
The connection numberDose (mg/kg)Time sedation (h)The size of the swelling ± SEM*The plasma concentration ± SEM (ng/ml)The plasma concentration ± SEM (ng/ml)
99410075,0 ± 6,278,6 ± 26,444,2 ± 8,90,047
100710,589,4 ± 2,2
30,586,3 ± 7,9
100,5of 97.8 ± 1,1
300,588,2 ± 5,7
10070,10,564,3 ± 11,224,4 ± 9,6BLQ
0,5 0,5to 78.7 ± 6,373,1 ± 14,5BLQ
10,598,1 ± 0,890,0 ± 11,02,3 ± 0,9
50,5and 99.8 ± 0,2398,0 ± 30,219,8 ± 15,7
8100,10,569,5 ± 19,6
0,50,560,9 ± 9,6
10,581,3 ± 8,4
50,5to 92.1 ± 3,1
9442139,3 ± 13,8NA4,3 ± 4,2
5148,4 ± 12,0NA3,5 ± 5,3
151 56,1 ± 9,2NA29,7 ± 25,9
9440,55-16,0 ± 17,322,1 ± 52,43,4 ± 9,1
0,5158,3 ± 13,41074,0 ± 492,385,1 ± 161,9
* Standard error

7.5.2 the effectiveness of the compounds in the simulation in mice arthritis induced by antibodies to collagen

In vivo efficacy of compounds in relation to autoimmune diseases can be demonstrated on the model of arthritis induced by antibodies to collagen (CAIA) in mice.

7.5.2.1 Model

Induced collagen arthritis (CIA) in rodents is often used as one of the experimental Talnah models in the case of tissue damage, mediated immune complex (IC). Introduction collagen type II mice or rats causes an immune reaction, which is characterized by the presence of inflammatory lesions of the cartilage and bones of peripheral joints, which is accompanied by swelling of the surrounding tissues. CIA is often used to assess the effectiveness of compounds that can potentially be used as drugs for the treatment of rheumatoid arthritis and other chronic inflammatory conditions.

In recent years, a new technology simulation CIA, based on the use of antibodies to the antitype II collagen with the intention of inducing CIA, mediated by antibodies. The advantages of this method are as follows: a short period of time that is required to induce disease (disease develops within 24-48 hours after intravenous (IV) injection of antibodies); arthritis can be induced as in CIA-susceptible and CIA-resistant breeds of mice; and in addition, the procedure is ideal for quick health-check anti-inflammatory therapeutics.

A mixture of monoclonal antibodies Arthrogen-CIA® (supplier company: Chemicon International Inc.), which induces arthritis, is injected mice of Balb/c (2 mg/mouse) on day 0. Forty-eight hours later injected intra-abdominal and what jectio 100 μl LPS *(25 µg). On the fourth day you may experience swelling of the claws. On the fifth day of one or both legs (especially the rear) begin to redden and swell. On the sixth day and for the next 1-2 weeks the redness and swelling of the feet will be maintained. In the research process, maintain records of the clinical features of inflammation to assess the intensity of edema of the legs. The degree of severity of arthritis register as a sum of points characterizing the state of both hind paws of each animal (the maximum possible number of points - 8). The degree of osalennosti damaged feet evaluated by measuring the diameter of the legs. Also keep records of body weight changes.

Treatment of animals begins with the induction of arthritis, ranging from zero days. The experimental and control connections enter one (q.d.) or two (b.i.d.) times a day orally (PO) based on previously established pharmacokinetic properties.

Upon completion of the study (1-2 weeks after induction of arthritis) mice are euthanized, trim tabs in place of the distal tibia with guillotine shears and weighed. Average ± standard error () of the averaged characteristics for each group determined each day based on clinical indicators of each individual animal, and at the end of ASCS is adowanie count and record the weight in the rear feet for each experimental group. Also get histopathological evaluation of the paws.

7.5.2.2 Results

Reducing osalennosti and swelling should be evident in animals treated with compounds according to the present invention, and the progression of arthritis should happen more slowly. Treatment of compounds (b.i.d.) be significantly reduced clinical arthritis compared with animals that were injected only filler.

7.5.3 the effectiveness of the compounds in the treatment of collagen-induced arthritis in rats

In vivo efficacy of the compounds according to the present invention in relation to autoimmune diseases has been demonstrated in models of collagen-induced arthritis (CIA) in rats.

7.5.3.1 model Description

Rheumatoid arthritis (RA) is characterized by chronic inflammation of the joints, which eventually leads to irreversible destruction of cartilage. Synovial tissue of patients with RA contain a large number of IC with immunoglobulin IgG. Despite the ongoing debate about the role of these complexes in the etiology and pathology of this disease, the communication IC with hematopoietic cells by using FcγR receptors.

CIA is a widely accepted animal model of RA, which is a chronic inflammatory synovitis characterized coord is m pannus and degradation of the joints. In this model, the subcutaneous administration of native collagen type II emulsified with incomplete adjuvant-blockers, leads to the development of inflammatory arthritis for 10 or 11 days and the subsequent destruction of the joints in the range from 3 to 4 weeks.

7.5.3.2 the study Protocol

At day 0 group syngenetic rats LOU were immunized with native collagen type II CII/IFA (University pcs. California in Los Angeles, project Manager - E. bran (Brahn)). Starting from the day of onset of arthritis (day 10), can be treated with a total of 59 rats using either the control filler or compound according to the present invention, using one of four doses (1, 3, 10 and 30 mg/kg, q.d. oral).

7.5.3.3 Results

Assessment of hind limb produced daily using a standardized method based on the degree of inflammation of the joints. Upon completion of the study (day 28), you can get clear digital x-ray images of the rear limbs. These limbs can also be evaluated for histopathological changes. Quantitative measurement of IgG antibodies to native collagen CII can be performed using enzyme immunoassay ELISA with a fourfold repetition.

Although the present invention has been described using certain who's details to facilitate the understanding, it is clear that allowed certain changes and modifications within the following claims. Accordingly described examples should be considered as illustrative and not restrictive, and the invention is not limited to the above details, but may be modified within the scope and equivalents of the following claims.

All references and patents made in the text of this proposal, included as a reference for all purposes.

1. The compound 2,4-pyrimidinediamine corresponding to the structural formula:

including its pharmaceutically acceptable salt,
where L1is a direct link;
L2is a direct link;
R2is a phenyl group, three times substituted by three groups of R8;
R4is
X represents N;
Y is selected from the group consisting of O, NH, S, SO and SO2;
Z is selected from the group consisting of O and NH; provided that when Y is selected from the group consisting of NH, S, SO and SO2then Z is not the same as Y;
R5is selected from the group consisting of R6and halogen;
each R6independently selected from the group consisting of hydrogen, halogen;
R8is selected from the group consisting of Ra, Rb, Ra/sup> substituted by one or more identical or different groups Raor Rb, -ORaand-O-CHRaRb;
each R35independently selected from the group consisting of hydrogen and
R8or alternatively, two groups of R35attached to the same carbon atom, taken together with the formation of the carbonyl group (=O) and the other two groups R35each independently of one another are selected from the group consisting of hydrogen and R8;
each Randindependently selected from the group consisting of hydrogen, (C1-C6) alkyl and (C3-C8) cycloalkyl;
each Rba suitable group which is independently selected from the group consisting of-ORd, halogen, -CF3, -C(O)NRcRcand-OC(O)ORd;
each Rcindependently is Ra;
each Rdindependently is Ra;
provided that
N2-(3-chloro-4-methoxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine;
N2-(3-chloro-4-hydroxy-5-were)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine; and
N2-(3,5-dimethyl-4-methoxyphenyl)-N4-(2,2-dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine are excluded.

2. The compound of the structural formula:

and its pharmaceutically acceptable salts, which are:
R2is selected from the group consisting of (C1-C6) alkyl, phenyl, optionally substituted by one or more identical or different groups R8, 5-6-membered cyclogeranyl containing 1-2 heteroatoms selected from nitrogen, oxygen, or sulfur, optionally condensed with a benzene ring and optionally substituted substituted by one or more identical or different groups R8;
R4is selected from the group consisting of hydrogen, 5-6-membered cyclogeranyl containing 1-2 heteroatoms selected from nitrogen, oxygen, or sulfur, optionally condensed with a benzene ring and optionally substituted by one or more identical or different groups R8and 5-6-membered heteroaryl containing 1-2 heteroatoms selected from nitrogen, oxygen and sulfur optionally substituted by one or more identical or different groups R8;
R8is selected from the group consisting of Ra, Rbsubstituted by one or more identical or different groups Raor Rb,
-ORaand-O-(CH2)m-Rb;
each Raindependently selected from the group consisting of hydrogen, (C1-C6) alkyl, 5-membered heteroaryl containing 2 heteroatoms selected from nitrogen and oxygen, condensed with a benzene ring;
each is th R ba suitable group which is independently selected from the group consisting of =O, -ORd, -NRcRc, halogen, and-C(O)NRcRc;
each Rcindependently is Ra,
each Rdindependently is Ra;
R55is selected from the group consisting of(C1-C6) alkyl and
each index m is independently an integer from 1 to 3.

3. The compound of the structural formula:

and its pharmaceutically acceptable salts in which:
R2represents a

R4is selected from the group consisting of hydrogen, 5-6-membered cyclogeranyl containing 1-2 heteroatoms selected from nitrogen, oxygen, or sulfur, optionally condensed with a benzene ring and optionally substituted by one or more identical or different groups R8and 5-6-membered heteroaryl containing 1-2 heteroatoms selected from nitrogen, oxygen and sulfur optionally substituted by one or more identical or different groups R8;
R8is selected from the group consisting of Ra, Rb, Rasubstituted by one or more identical or different groups Raor Rb,
ORasubstituted by one or more identical or different groups Ra
or Rb, -(CH2)m-Rb, -(CHRa)m-Rb,
O(CH2)m-Rb;
each Raindependently selected from the group consisting of hydrogen and (C1-C6) alkyl;
each Rba suitable group which is independently selected from the group consisting of =O, -ORd(C1-C3) halogenations, -NRcRc, halogen, -C(O)RbC(O)ORdand
-C(O)NRcRc;
each Rcindependently is Ra;
each Rdindependently is Ra;
each index m is independently an integer from 1 to 3.

4. The compound 2,4-pyrimidinediamine selected from the group consisting of
N4-[(2,3-Dihydro-1,4-benzodioxan-2-yl)methyl]-N2-(3, 5dimethylphenyl)-5-fluoro-2,4-pyrimidinediamine;
N4-[(2,3-Dihydro-1,4-benzodioxan-2-yl)methyl]-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine;
N4-[(2,3-Dihydro-1,4-benzodioxan-2-yl)methyl]-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine;
N2-(3-Chloro-4-methoxyphenyl)-N4-[(2,3-dihydro-1,4-benzodioxan-2-yl)methyl]-5-fluoro-2,4-pyrimidinediamine;
N4-[(2,3-Dihydro-l,4-benzodioxan-2-yl)methyl]-5-fluoro-N2-(indazol-6-yl)-2,4-pyrimidinediamine.

5. The compound 2,4-pyrimidinediamine selected from the group consisting of
N4-(3,4-Dihydro-2,2-dimethyl-4H-benzo[l,4]oxazin-6-yl)-5-fluoro-N2-[3-(N-methylamino)carbonintensity]-2,4-pyrimidinediamine;
N2-(3-Chloro-4-methoxy-5-methylp the Nile)-N4-(3,4-dihydro-2,2-dimethyl-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-2,4-pyrimidinediamine and
N4-(3,4-Dihydro-2,2-dimethyl-4H-benzo[1,4]oxazin-6-yl)-N2-(3,5-acid)-5-fluoro-2,4-pyrimidinediamine.

6. The compound 2,4-pyrimidinediamine structural formula:

and its pharmaceutically acceptable salts, in which:
R2represents;
R4represents;
R5represents a fluorine atom;
R6represents a hydrogen atom;
Y is selected from the group consisting of O, S, SO; and NR37;
Z is selected from the group consisting of OH, SO, SO2, NH and NR37provided that Z is not the same as Y;
each of R35independently selected from the group consisting of hydrogen and R8or alternatively, two R35attached to the same carbon atom, taken together with the formation of the carbonyl group (=O), and the remaining two groups of R35each independently of one another are selected from the group consisting of hydrogen and R8;
R8is selected from the group consisting of Ra, Rb, Rasubstituted by one or more identical or different groups Raor Rb,
-ORasubstituted by one or more of odinakovimi or different groups Raor Rb-(CH2)m-Rb, -O-(CH2)m-Rband
-O-CRa(Rb) 2;
each Raindependently selected from the group consisting of hydrogen, (C1-C6) alkyl;
each Rba suitable group which is independently selected from the group consisting of =O, -ORd, -NRcRc, halogen, -C(O)ORd; -C(O)ORd, -C(O)NRwithRwith;
each Rwithindependently is Ra;
each Rdindependently is Ra;
each index m is independently an integer from 1 to 3; and
R37is selected from the group consisting of hydrogen and progroup selected from the group consisting of RaRband-CRaRb-O-C(O)R8.

7. The connection according to claim 6, in which Y is oxygen, Z is an NH and one or more R35represents an alkyl group.

8. The connection according to claim 6, in which R4represents.

9. The connection according to claim 6, in which R4represents.

10. The connection according to claim 6, in which Y is oxygen, Z is an NH.

11. The compound 2,4-pyrimidinediamine selected from the group consisting of
N4-(3,4-Dihydro-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine,
N4-(3,4-Dihydro-3,3-dimethyl-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine,
5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-N4-(3-OK, what about-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine,
5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-7-yl)-2,4-pyrimidinediamine,
5-fluoro-N4-[2-(2-hydroxyethyl)-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl]-N2-[3-(oxazol-2-yl)phenyl] -2,4-pyrimidinediamine,
N4-(3,4-Dihydro-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
N4-(3,4-Dihydro-3,3-dimethyl-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine,
(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[4-(oxazol-5-ylphenyl]-2,4-pyrimidinediamine,
5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-7-yl)-2,4-pyrimidinediamine,
5-fluoro-N4-[2-(2-hydroxyethyl)-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl]-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
N4-(3,4-Dihydro-4-methyl-2H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
N4-(3,4-Dihydro-4-methyl-2H-benzo[1,4]oxazin-7-yl)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
5-fluoro-N4-(4-methyl-3-oxo-2H-benzo[1,4]oxazin-7-yl)-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
5-fluoro-N4-(4-methyl-3-oxo-2H-benzo[1,4]oxazin-6-yl)-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
N4-(3,4-Dihydro-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
N4-(3,4-Dihydro-3,3-dimethyl-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
5-fluoro-N2-[3-(oxazol-5-yl)F. the Nile]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-7-yl)-2,4-pyrimidinediamine,
N4-(3,4-Dihydro-4-methyl-2H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
N4-(3,4-Dihydro-4-methyl-2H-benzo[1,4]oxazin-7-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
N4-(3,4-Dihydro-3,3-dimethyl-2H,4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine,
5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-2,4-pyrimidinediamine,
(S)-5-fluoro-N4-(2-methyl-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl)-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine,
5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-N4-(3-oxo-2H,4H-benzo[1,4]oxazin-7-yl)-2,4-pyrimidinediamine,
5-fluoro-N4-[2-(2-hydroxyethyl)-3-oxo-2H,4H-benzo[1,4]oxazin-6-yl]-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine,
N4-(2,3-Dihydro-4-methyl-2H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine,
5-fluoro-N4-(4-methyl-3-oxo-2H-benzo[1,4]oxazin-7-yl)-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine,
5-fluoro-N4-(4-methyl-3-oxo-2H-benzo[1,4]oxazin-6-yl)-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine,
N4-(2,2-Dimethyl-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine,
N4-(2,2-Debtor-3-oxo-4H-benzo[1,4]oxazin-6-yl)-5-fluoro-N2-[3-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine,
N4-(4-N-tert-Butoxycarbonylamino-3,4-dihydro-2H-1-benzopyran-6-yl)-5-fluoro-N2-[3-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
N4-(4-N-tert-Butoxycarbonylamino-3,4-dihydro-2H-1-benzopyran-6-yl)-5-fluoro-N2-[4-(oxazol-5-yl)phenyl]-2,4-PI is imagineasia,
N4-(4-N-tert-Butoxycarbonylamino-3,4-dihydro-2H-1-benzopyran-6-yl)-5-fluoro-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine,
5-fluoro-N4-(4-hydroxy-3,4-dihydro-2H-1-benzopyran-6-yl)-N2-[4-(oxazol-5-yl)phenyl]-2,4-pyrimidinediamine,
5-fluoro-N4-(4-hydroxy-3,4-dihydro-2H-1-benzopyran-6-yl)-N2-[4-(oxazol-2-yl)phenyl]-2,4-pyrimidinediamine.

12. The compound 2,4-pyrimidinediamine structural formula:

and its pharmaceutically acceptable salts, in which:
R2representswhere Y represents O, S, NH,
NR37; or NR35;
R4represents a 3-6-membered cyclogeranyl containing 1-2 heteroatoms in the ring, optionally condensed with a pyridine ring or a benzene and optionally substituted by one or more identical or different groups R8;
R5represents a fluorine atom;
R6represents a hydrogen atom;
R8is selected from the group consisting of Ra, Rb, Rasubstituted by one or more identical or different groups Raor Rb, -ORasubstituted by one or more identical or different groups Raor Rband-O(CH2)m-Rb;
each Raindependently selected from the group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl; each Rba suitable group which is independently selected from the group consisting of =O, -ORd, -NRcRc, halogen,
- C(O)Rdand-C(O)ORb;
each Rcindependently is a protecting group selected from the group consisting of formyl, acetyl, TRIFLUOROACETYL, benzyl, benzyloxycarbonyl, tert-butoxycarbonyl;
each Rdindependently is Ra;
each index m is independently an integer from 1 to 3;
R35represents hydrogen or R8;
R36represents hydrogen or alkyl; and
R37is selected from the group consisting of hydrogen and progroup selected from the group consisting of Ra, Rb, -CRaRb-O-C(O)R8and
- C(O)R8.

13. The compound 2,4-pyrimidinediamine selected from the group consisting of:
N4-(1-tert-Butoxycarbonylamino-3-yl)-5-fluoro-N2-(4-morpholinomethyl)-2,4-pyrimidinediamine,
N2-[4-(4-Acetylpiperidine)phenyl]-N4-(1-tert-butoxycarbonylamino-3-yl)-5-fluoro-2,4-pyrimidinediamine,
N2-[3-(4-Acetylpiperidine)phenyl]-N4-(1-tert-butoxycarbonylamino-3-yl)-5-fluoro-2,4-pyrimidinediamine,
N4-(1-tert-Butoxycarbonylamino-3-yl)-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine,
N4-(Azetidin-3-yl)-5-fluoro-N2-(4-morpholinomethyl)-2,4-pyrimidinediamine,
N2-[4-(4-Acetylpiperidine)phenyl]-N4-(azetidin-3-yl)-5-fluoro-24-pyrimidinediamine,
N4-(Azetidin-3-yl)-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine,
N4-(Azetidin-3-yl)-5-fluoro-N2-(3-morpholinomethyl)-2,4-pyrimidinediamine,
N2-[3-(4-Acetylpiperidine)phenyl]-N4-(azetidin-3-yl)-5-fluoro-2,4-pyrimidinediamine,
N4-(1-tert-Butoxycarbonylamino-3-yl)-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine,
N4-(Azetidin-3-yl)-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine,
N4-(Azetidin-3-yl)-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine,
(S)-N4-(1-Benzylpyrrolidine-3-yl)-5-fluoro-N2-(4-morpholinomethyl)-2,4-pyrimidinediamine,
(S)-N2-[4-(4-Acetylpiperidine)phenyl]-N4-(1-benzylpyrrolidine-3-yl)-5-fluoro-2,4-pyrimidinediamine,
(S)-N4-(1-Benzylpyrrolidine-3-yl)-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine,
(S)-N4-(1-Benzylpyrrolidine-3-yl)-N2-[4-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine,
(S)-N4-(1-Benzylpyrrolidine-3-yl)-5-fluoro-N2-(3-morpholinomethyl)-2,4-pyrimidinediamine,
(S)-N2-[3-(4-Acetylpiperidine)phenyl]-N4-(benzylpyrrolidine-3-yl)-5-fluoro-2,4-pyrimidinediamine,
(S)-N4-(1-Benzylpyrrolidine-3-yl)-5-fluoro-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine,
(S)-N4-(1-Benzylpyrrolidine-3-yl)-N2-[3-(4-ethoxycarbonylpyrimidine)phenyl]-5-fluoro-2,4-pyrimidinediamine
and its pharmaceutically acceptable salts.

14. A compound selected from the group consisting of:
5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-N4-(1,2,2,,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamine,
5-fluoro-N2-[3-(4-methylpiperazine)phenyl]-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamine,
N2-[3-Chloro-4-(4-methylpiperazine)phenyl]-5-fluoro-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamine,
5-fluoro-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamine,
5-fluoro-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-N2-[3-trifluoromethyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine,
N4-(1-Ethoxycarbonylpyrimidine-4-yl)-5-fluoro-N2-[4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine,
N4-(1-Ethoxycarbonylpyrimidine-4-yl)-5-fluoro-N2-[3-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine,
N2-[3-Chloro-4-(4-methylpiperazine)phenyl]-N4-(1-ethoxycarbonylpyrimidine-4-yl)-5-fluoro-2,4-pyrimidinediamine,
N4-(1-Ethoxycarbonylpyrimidine-4-yl)-5-fluoro-N2-[3-methyl-4-(4-methylpiperazine)phenyl]-2,4-pyrimidinediamine,
N4-(1-Ethoxycarbonylpyrimidine-4-yl)-5-fluoro-N2-[4-(4-methylpiperazine)-3-triptoreline]-2,4-pyrimidinediamine,
N2-[2-(4-Ethylpiperazine)pyrid-5-yl]-5-fluoro-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamine,
N4-(1-Ethoxycarbonylpyrimidine-4-yl)-N2-[2-(4-ethylpiperazine)pyrid-5-yl]-5-fluoro-2,4-pyrimidinediamine,
5-fluoro-N2-[2-(4-methylpiperazine)-3-methylpiperid-5-yl]-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamine,
5-fluoro-N2-[2-(4-methylpiperazine)-4-methylpiperid-5-yl]-N4-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pyrimidinediamine,
or its pharmaceutically acceptable salts

15. The compound 2,4-pyrimidinediamine structural formula:

and its pharmaceutically acceptable salts, in which:
R2is selected from the group consisting of phenyl, optionally substituted by 1-3 identical or different groups R8, 5-6-membered heteroaryl containing 2 heteroatoms selected from nitrogen and oxygen, and optionally condensed with benzene;
R4represents;
R5represents a fluorine atom;
R6represents a hydrogen atom; and
R8is selected from the group consisting of Ra, Rb, Rasubstituted by one or more identical or different groups Raor Rb-ORaand-O-(CH2)m-Rb;
each Raindependently selected from the group consisting of hydrogen and (C1-C6) alkyl;
each Rba suitable group which is independently selected from the group consisting of =O, -ORdand-OC(O)NRcRc;
each Rcindependently is Ra;
each Rdindependently is Ra;
each index m is independently an integer from 1 to 3.

16. The connection indicated in paragraph 15, in which R2representsand each R46, R47and R48independently selected from the group comprised the soup from hydrogen, of alkyl, alkoxy, hydroxyl, halogen, isoxazol, piperazine derivatives, N-alkylpiperazine, morpholine and CH3NHC(O)CH2O-, provided that none of the groups R46, R47and R48is not hydrogen, and that, if one of the groups R46, R47or R48is isoxazol, piperazine derivatives, N-alkylpiperazine, morpholine or CH3NHC(O)CH2O-then the rest of the group R46, R47or R48are hydrogen.

17. The connection 15, which
R2is selected from the group consisting ofand;
each of the groups R21, R22and R23independently of one another is C1-Salcininky group.

18. The connection 17 in which each of the groups R22and R23or R21and R22or R21,
R22and R23is a methyl group.

19. The compound 2,4-pyrimidinediamine structural formula:

and its pharmaceutically acceptable salts, in which:
R2isor
R4is selected from the group consisting of
and
R5represents a fluorine atom;
R6represents a hydrogen atom;
R represents consisting of Rsup> a;
R21represents a C1-Saltillo group;
R23represents a C1-Saltillo group;
each R28individually represents halogen or C1-Celecoxi-group;
R29represents (C1-C6)alkyl;
each Raindependently selected from the group consisting of hydrogen and (C1-C6) alkyl.

20. The connection according to claim 19, in which R28is a methoxy group.

21. The connection according to claim 19, in which R21is a methyl group.

22. The connection according to claim 19, in which each R28is chlorine.

23. The connection according to claim 19, in which R21is a methyl group and R28is chlorine.

24. The compound 2,4-pyrimidinediamine structural formula:

and its pharmaceutically acceptable salts, in which:
R2isor;
R4is selected from the group consisting ofand
R5represents a fluorine atom;
R6represents a hydrogen atom;
R8is selected from the group consisting of RaRb, Rasubstituted by one or more identical or different groups Raor Rb, -ORa, -NH-(CH2)m-Rb;
R21represents a C1-Saltillo group
each R28individually represents halogen or C1-Celecoxi;
X is selected from the group consisting of N and CH;
Y is selected from the group consisting of O and NH;
Z is selected from the group consisting of O and NH, provided that Z is not the same as Y;
each R35independently selected from the group consisting of hydrogen and
Raor alternatively, two R35attached to the same carbon atom, taken together with the formation of the carbonyl group (=O), and the other two groups
R35each independently of one another are selected from the group consisting of hydrogen and R8;
each Raindependently selected from the group consisting of hydrogen, (C1-C6) alkyl, 5-6-membered cyclogeranyl containing 1-2 heteroatoms in the cycle selected from nitrogen, oxygen and sulfur;
each Rba suitable group which is independently selected from the group consisting of =O, -NRcRc, halogen, -CF3,
-S(O)2NRcRc;
each Rcindependently is Raor alternatively, each Rctaken together with the nitrogen atom to which it is attached, with the formation of 5-6-membered cyclogeranyl containing 1-2 heteroatoms in the cycle, selected from nitrogen and oxygen, and which may be optionally substituted by one or more of odinakovymi different groups of R aor suitable groups Rb;
each Rdindependently is Ra;
each index m is independently an integer from 1 to 3;
R50represents a C1-Saltillo group, or -(CH2)qOH;
q is calm a number from 1 to 6; and
R52represents an alkyl group or substituted R8alkyl group.

25. The connection point 24, in which R21represents a methyl group.

26. The connection point 24, in which each R28represents chlorine.

27. The connection point 24, in which R21represents a methyl group and R28represents chlorine.

28. The connection point 24, in which R50represents-CH2CH2HE.

29. The connection point 24, in which R52represents trifluoromethyl.

30. The connection point 24, in which R50represents a methyl group.

31. The connection point 24, in which each R28represents chlorine.

32. The connection point 24, in which R50represents a methyl group and R28represents chlorine.

33. The compound 2,4-pyrimidinediamine structural formula:

and its pharmaceutically acceptable salts, in which:
R2represents
R4is cycloalkyl;
R 5represents a fluorine atom;
R6represents a hydrogen atom;
R21represents an alkyl group; and
R30represents an alkyl group or halogen.

34. Connection p, in which R21represents a methyl group.

35. The compound according to claim 1, in which
R4is.

36. The compound according to claim 1, in which
R2representsand R4representsR31represents (C1-C6)alkyl group.

37. Connection p, in which
R4is.

38. Connection p, in which Y is O, Z represents NH and X represents N.

39. The Union, representing N4-(2,2-Dimethyl-3-oxo-4H-5-pyrid[1,4]oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine or its pharmaceutically acceptable salt.

40. Pharmaceutical composition having effects in autoimmune disorders, containing an effective amount of a compound according to any one of claims 1 to 39 as an active ingredient and a pharmaceutically acceptable carrier, diluent, excipient or excipient.

41. The use of compounds according to any one of claims 1 to 39 for the manufacture of a medicine for treatment auto Munich diseases.



 

Same patents:

FIELD: chemistry; pharmacology.

SUBSTANCE: compounds of formula (I) as inhibitors of phosphotyrosine phosphotase 1B and their pharmaceutically acceptable salts, their application, based pharmaceutical composition and method of production. In general formula (I) , R1 indicates phenyl, naphthyl, thionaphthyl, pyridyl. Phenyl, naphthyl, thionaphthyl and pyridyl can be single- or multiple-substituted with F, Cl, Br, (CH2)0-2OH, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkinyl, CF3, OCF3, N(R9)(R10), piperidinone, piperazine, piperazinone, N-(C1-C6-alkylene)-piperazine, N-(C1-C6-alkylene)-piperazinone, morpholine, thiomorpholine, NO2, CN, O-(C1-C6)-alkyl, S(O)0-2-(C1-C6)-alkyl, SO2-N(R9)(R10), CO-(C1-C6)-alkyl, -COOH, (C1-C6)-alkylene-COOH, COO(C1-C6)-alkyl, (C1-C6)-alkyleny-COO(C1-C6)-alkyl, (C3-C10)-cycloalkyl, phenyl. These piperidinone, piperazine, piperazinone, N-(C1-C6-alkylene)-piperazine, N-(C1-C6-alkylene)-piperazinone, morpholine, thiomorpholine, and phenyl rings can be single- or multiple-substituted with F, Cl, Br, (CH2)0-2OH, COOH, CN, NO2, O-(C1-C6)-alkyl, -NH-O-(C1-C6)-alkyl, -(CO)-NH-O-(C1-C6)-alkylene-N(R9)(R10), -(CO)-(C1-C6)-alkyl, -(C1-C6)-alkyl, CF3, OCF3, N(R9)(R10); R2 indicates H, (C1-C6)-alkyl, COOH, (C1-C6)-alkylene-COOH, COO(C1-C6)-alkyl, (C1-C6)-alkylene-COO(C1-C6)-alkyl; R3 indicates H, (C1-C6)-alkyl, (C1-C6)-alkylenphenyl, -C(O)-phenyl, (C1-C6)-alkylenheterocycle, where heterocycle represents 5-6-merous heterocyclic ring containing 1-2 heteroatoms, chosen of nitrogen and oxygen, CO-(C1-C6)alkyl; R4, R5 indicate H; R6 indicates H, R9 indicates H, (C1-C4)-alkyl; R10 indicates H, (C1-C4)-alkyl.

EFFECT: applications for treating diseases mediated with phosphotyrosine phosphotase 1B activity, such as diabetes type II, lipidosis and carbohydrate metabolic imbalance, insulin resistivity, reduced sugar content in blood.

9 cl, 2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: there is disclosed compounds of formula II , where each R2 independently stands for H, halogen, cyano, NO2, OR5, NR6R7, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, arylalkyl, substituted arylalkyl, heterocycloalkyl or substituted heterocycloalkyl; B represents O, S, SO or SO2; each W and X independently represents C or N; n is within 0 to 4 if both W and X represent C, 0 to 3, if either X or W represent N, and 0 to 2 if both X and W represent N; R3, R5, R6, R7 are independently chosen from H, alkyl, substituted alkyl, alkenyl, alkinyl, substituted alkinyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo; R4 represents optionally substituted 5-6-merous heteroaryl containing nitrogen atom provided (a) if R4 stands for pyridyl, R4 is not substituted with both hydroxy and methoxy groups; and (b) R4 stands for pyrimidinyl, it is n-substituted =O; A is chosen from following compounds of formula: , where D stands for S or O; m is within 0 to 6; R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26 and R27 are independently chosen from H, halogen, NR30R31, OR32, CO2R33, SO2R36, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkinyl, substituted alkinyl, -CN, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl or substituted heterocycloalkyl; R28 and R29 are independently chosen from H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl or together they form carbocyclic or heterocyclic ring consisting of 3 to 8 atoms; and R30, R31, R32, R33 and R36 are independently chosen from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkinyl, substituted alkinyl, cycloalkyl, substituted cycloalkyl, alkoxycarbonyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, heterocycloalkyl or substituted heterocycloalkyl as pharmaceutical composition for cancer treatment containing compound of formula II.

EFFECT: production of new compounds and based pharmaceutical composition applied for cancer treatment.

18 cl, 147 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to the method of producing compounds with formula I and to their pharmaceutical salts. In formulae I, II, IV, V: R1 or R2 represent H, -(CH2)t(5-member heterocyclic compound), where t equals 4 and where the heterocyclic compound contains one nitrogen atom as the heteroatom, R3 is -(CH2)t(C6-C10aryl), where t equals 1. The given R3 groups are optionally substituted with 3 R4 groups. Each R4 is independently chosen from halogen. R8 is C1-C10alkyl, R9 is C1-C10alkyl, and n equals 2.

EFFECT: treatment of hyper-proliferative diseases using new intermediate compounds with formulae II, IV, V.

15 cl, 2 dwg, 11 ex

FIELD: chemistry.

SUBSTANCE: compounds of the invention have chemokine antagonistic properties and can be applied in treatment of immunoinflammatory diseases, such as atherosclerosis, allergy diseases. In general formula (I) R1 is hydrogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxyl, cyclopropylmethoxy group, (C1-C4)-alkylthio group; R2 is halogen atom, (C1-C8)-alkyl, perfluoro-(C1-C4)-alkyl, (C3-C10)-cycloalkyl, phenyl, (C1-C8)-alkoxyl, values of the other radicals are indicated in the claim of the invention.

EFFECT: improved properties.

14 cl, 7 tbl, 20 dwg, 17 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and pharmaceutically acceptable salts. Claimed compounds have modulation effect on CB cannabinoid receptor. In the general formula (I) , R and R1 are the same or different and are phenyl optionally substituted by 1-3 substitutes Y, where Y is substitute selected out of group including chlorine, iodine, bromine, fluorine, on condition that X is not a sub-group (ii); or one of R and R1 radicals is phenyl group, while the other radical is formed or linear C2-8-alkyl group or benzyl group; X is one of the sub-groups (i) or (ii). Also invention concerns application of the compounds in obtaining pharmaceutical composition, pharmaceutical composition with modulation effect on CB cannabinoid receptor, and compound of the general formula (IV) with radical values as indicated in the claim.

EFFECT: enhanced efficiency of composition and treatment method.

5 cl, 1 tbl, 25 ex

FIELD: chemistry.

SUBSTANCE: invention concerns method of treatment, alleviation and/or prevention of neurological state, particularly neurodegenerative disorders, involving administration of effective quantity of compound with formula I: . Also invention concerns application of compound of the formula I as neurotherapeutical, neuroprotective or antimyloid agent, pharmaceutical or veterinary composition for treatment, alleviation and/or prevention of neurological states, and compounds of the formula I on the following additional terms: (b) if R3, R and R' are H, and R2 is (CH2)2NR9R10, then both R9 and R10 are not ethyl or methyl; (c) if R3, R and R' are H, and R2 is (CH2)2NR9R10, then both R9 and R10 are not hydrogen or ethyl; (d) if R3, R and R' are H, and R2 is NR11R12, then both R11 and R12 are not hydrogen; (e) if R3, R and R' are H, and R2 is COR6, then R6 is not H, OH or CH2Cl; (f) if R3, R and R' are H, and R2 is not CH3 or CH2Cl; (g) if R3, R and R' are H, and R2 is HCNN R9R10, then both R9 and R10 are not H.

EFFECT: efficient treatment, alleviation and prevention of neurological state.

24 cl, 14 tbl, 21 ex, 14 dwg

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) , where R1 is phenyl optionally substituted by halogen, cyano, C1-4alkyl or C1-4haloalkyl; R2 is hydrogen, C1-6alkyl or C3-6cycloalkyl; and R3 is a group with NH or OH and calculated or measured pKa from 1.0 to 8.0, selected out of: 2-oxo-thiazol-5-yl with C1-4fluoroalkyl, optionally substituted phenyl group, optionally substituted heterocyclyl group or CH2S(O)2(C1-4alkyl) group in position 4; 2-oxo-oxazol-5-yl with C1-4fluoroalkyl or CH2S(O)2(C1-4alkyl) in position 4; 1H-1,2,3-triazol-4-yl with C1-4alkyl, C3-6cycloalkyl, C1-4fluoroalkyl, S-R4 (where R4 is C1-4alkyl, C1-4fluoroalkyl or C3-6cycloalkyl), NHS(O)2(C1-4alkyl), N(C1-4alkyl)S(O)2(C1-4alkyl), phenyl group, heterocyclyl group or CH2S(O)2C1-4alkyl) group in position 5; 4-oxo-1H-1,4-dihydropyridine-3-yl with C1-4fluoroalkyl in position 2; 2,6-dioxo-1H-1,2,3,6-tetrahydropyrimidine-4-yl with C1-4alkyl, C3-6cycloalkyl or CH2(C1-3fluoroalkyl) in position 3 and optionally substituted in one or more other ring positions; 6-oxo-1H-1,6-dihydropyridine-3-yl with C1-4fluoroalkyl, cyano or phenyl in position 2 and/or in position 5 and optionally substituted in one or more other ring positions; 6-oxo-1H-1,6-dihydropyridine-3-yl with CH2CO2H at ring nitrogen atom and optionally substituted in one or more other ring positions; 2H-tetrazol-5-yl; CO2H, CH2CO2H or OCH2CO2H group at optionally substituted phenyl, optionally substituted CH2O phenyl or optionally substituted naphtyl ring or optionally substituted acylated dihydroisoquinolinyl ring; or group NHS(O)2(C1-4alkyl) at optionally substituted aromatic heterocyclic ring; or their tautomer where possible; in indicated positions where heterocyclyl ring in R3 can be optionally substituted, it can be optionally substituted by fluoro, chloro, bromo, C1-4alkyl, C3-6cycloalkyl, C1-4fluoroalkyl, S-R4 (where R4 is C1-4alkyl, C1-4fluoroalkyl or C3-6cycloalkyl), cyano, S(O)2(C1-4alkyl); in indicated positions where phenyl or naphtyl ring in R3 can be optionally substituted, it can be optionally substituted by halogen, cyano, C1-4alkyl, C1-4alkoxy, C1-4fluoroalkyl, OCF3, SCF3, nitro, S(C1-4alkyl), S(O)(C1-4alkyl), S(O)2(C1-4alkyl), S(O)2NH(C1-4alkyl), S(O)2N(C1-4alkyl)2, NHC(O)(C1-4alkyl) or NHS(O)2(C1-4alkyl); or its pharmaceutically acceptable salts. Also invention concerns compounds of formula (I), method of obtaining compounds of any of claims 1-12, as well as pharmaceutical composition.

EFFECT: obtaining novel bioactive compounds with chemokine receptor activity modulation effect.

16 cl, 51 ex

FIELD: chemistry.

SUBSTANCE: invention claims derivatives of pyridazin-3(2H)-one of formula (I), where R1, R2 and R4 are organic radicals described in the claim 1, R3 is cyclic group described in the claim, and R5 is phenyl or heteroaryl group described in the claim. Compounds of formula (I) inhibit phosphodiesterase 4 (PDE-4) and can be applied in treatment of various diseases or pathological states alleviated by PDE-4 inhibition, and in medicine production for treatment of aforesaid diseases. Also invention claims method of obtaining these compounds and intermediate compounds for their obtainment.

EFFECT: obtaining compounds which can be used in treatment of various diseases or pathological states and in medicine production for treatment of aforesaid diseases.

25 cl, 28 tbl, 243 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new compounds with formula I: , where L represents radical , in which R1 represents H, C1-4alkyl; n represents 0 or 1; or L represents radical , in which R1 represents H, C1-4alkyl; m equals 1; R represents H, halogen, C1-C4alkyl or C1-C4-alkoxy; Z represents a bond, -C(O)NH-, O or S; p is an integer from 1 to 5; Q represents a bond with the condition that, Z is not a bond, when p equals 1; or represents O, S or -C(O)NR6-, where R6 represents H, C1-4alkyl or C3-6cycloalkyl; or W and R6 together with a nitrogen atom, to which they are bonded, form or or Q represents -NR6-, or in the condition that, p is not equal to 1; W represents , , , , ,

, , ,

, , ,

, , , ,

, , , ,

, , , ,

, , , , ,

, , , , , and

.

EFFECT: obtaining compounds with agonistic activity towards PPAR receptors, which enables them to be used in pharmaceutical compositions and methods of treating conditions, mediated by these receptors.

12 cl, 7 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to compounds of formula 1 and their pharmaceutically acceptable salts as inhibitors of post-proline aminopepdidases, as well as to pharmaceutical composition based on them and application for manufacturing such composition, and to method of inhibition with their application. Compounds can be applied for treatment of diseases mediated by activity of post-proline aminopeptidases, such as type II diabetes and disturbed tolerance to glucose. In general formula 1 ,

either G1 represents -CH2-X2-(CH2)a-G3, and G2 represents H, or G2 represents -CH2-(CH2)a-G3, and G1 represents H; G3 is selected from group according to general formula 2