Compound, composition for insect control, methods for insect control

FIELD: organic chemistry, insecticides.

SUBSTANCE: invention describes compound of the formula (I): wherein B represents oxygen atom (O) or -NR1; J represents 5-membered heteroaromatic ring representing group of the formula (J-1): optionally substituted with 1-2 radicals R5 wherein Q represents -NR5; each X, Y and Z represents independently nitrogen atom (N), -CH or - CR5; B1 represents O; R2 represents hydrogen atom (H) or (C1-C6)-alkyl optionally substituted with one halogen atom, or (C2-C6)-alkynyl; or R1 and R2 taken in common form a binding chain consisting of 2-3 members and comprising at least one carbon atom, optionally comprising one carbon atom as -C(=O), optionally substituted with R3 wherein R3 represents (C1-C2)-alkyl; each R represents independently H, (C1-C6)-alkyl, halogen atom or -CN; each R5 represents independently (C1-C6)-halogenalkyl or halogen atom, or each ring is substituted with one R6; each R6 represents independently halogen atom; n represents a whole number 1 or 2. Also, invention describes a composition used for control of insects and comprising the biologically effective dose of compound of the formula (I) and at least one additional component chosen from group comprising surface-active substances, solid and liquid diluting agents, and methods for control of insects with using compositions based on compounds of the formula (I) and compounds of the formula (I). Proposed compounds of the formula (I) possess insecticide activity and can be used in agriculture.

EFFECT: valuable insecticide properties of compounds and compositions.

11 cl, 26 tbl, 4 ex

 

This invention relates to certain aminobenzamidine, iinvestigation and aminobenzoyl, their N-oxides, salts and compositions, suitable for agricultural and non-agricultural applications, including applications listed below, and to methods of combating invertebrate pests in agricultural and non-agricultural applications.

Suppression of invertebrate pests is very important to achieve high efficiency for harvest. The damage of invertebrate pests of agricultural crops during their growing and storage, may cause a significant reduction in productivity and, thus, lead to higher cost products to the consumer. Combating invertebrate pests is also of great importance in forestry, for growing plants in greenhouses, ornamental plants and seedlings for nurseries, stored food and fiber products from livestock, household, public health and veterinary medicine. For use in these areas is available a large number of products, however there remains a need for new compounds that are more effective, less costly, less toxic, more safe for the environment or with different mechanisms of action.

In the publication NL 9202078 describes derivatives of N-acylanthranilic acid of the formula i as insecticide.

where X represents a direct bond; Y represents N or C1-C6alkyl; Z represents NH2, NH(C1-C3alkyl) or N(C1-C3alkyl)2and R1-R9independently represent H, halogen, C1-C6alkyl, phenyl, hydroxy, C1-C6alkoxy or1-C7acyloxy.

In the publication WO 00/31082 describes pyridine-4-enamines of the formula ii as fungicides

where a represents a condensed benzene ring; R1, R2and R3represent H, halogen, optionally substituted alkyl, alkenyl or quinil; R4represents optionally substituted phenyl; R5represents optionally substituted alkyl, alkenyl or quinil and R6represents H or optionally substituted alkyl, alkenyl or quinil.

This invention relates to a method of combating invertebrate pests comprising contacting bespozvonochnykh pest or its environment with a biologically effective amount of the compounds of formula I, its N-oxide or an agricultural acceptable salts of compounds (for example, in the form of a composition described in this image the shadow)

where In represents O, S or NR1;

J represents a phenyl ring, naftalina ring system, a 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring or ring system optionally substituted by 1-4 R5;

R1is To;

each To independently represents G; C1-C6alkyl, C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl, each of which is optionally substituted by one or more substituents selected from the group comprising halogen, G, CN, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C2-C6alkoxycarbonyl,2-C6alkylsulphonyl,3-C6trialkylsilyl, and phenyl, phenoxy or 5 - or 6-membered heteroaromatic ring, where each ring optionally substituted with one to three substituents, independently selected from R6; hydroxy; C1-C4alkoxy; C1-C4alkylamino; C2-C8dialkylamino; C3-C6cyclooctylamino; C2-C6alkoxycarbonyl and C2-C6alkylsulphonyl;

R2represents H or or

R1and R2taken together form a linking chain of 2-5 members, including at least one carbon member, optionally including not more than two carbon members of the form C(=O), optionally including one additional member selected from nitrogen and oxygen, and optionally substituted by 1-4 substituents selected from R3;

each R3independently represents C1-C4alkyl, halogen, CN, NO2or1-C2alkoxy;

G represents a 5 - or 6-membered nonaromatic carbocyclic or heterocyclic ring, optionally incorporating one or two ring members, selected from the group consisting of C(=O), SO and S(O)2and optionally substituted by 1-4 substituents selected from R3;

each R4independently represents H, C1-C6alkyl, C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl,1-C6halogenated,2-C6halogenoalkanes,2-C6halogenoalkanes,3-C6halogenosilanes, halogen, CN, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4allogenicity,1- 4halogenacetylenes,1-C4halogenallylacetic,1-C4alkylamino,2-C8dialkylamino,3-C6cyclooctylamino,2-C5alkoxyalkyl,1-C4hydroxyalkyl, C(O)R10, CO2R10C(O)NR10R11, NR10R11N(R11)CO2R10or3-C6trialkylsilyl or

each R4independently represents phenyl, benzyl, phenoxy or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R6;

each R5independently represents C1-C6alkyl, C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl,1-C6halogenated,2-C6halogenoalkanes,2-C6halogenoalkanes,3-C6halogenosilanes, halogen, CN, CO2H, CONH2, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4allogenicity,1-C4halogenacetylenes,1-C4halogenallylacetic,1-C4alkylamino,2-C8dialkylamino,3-C6cycloalkyl the Mino, With2-C6alkylsulphonyl,2-C6alkoxycarbonyl,2-C6alkylaminocarbonyl,3-C8dialkylaminoalkyl,3-C6trialkylsilyl or

each R5independently represents phenyl, benzyl, benzoyl, phenoxy, 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring or each ring system is optionally substituted with one to three substituents, independently selected from R6or

two groups of R5when attached to adjacent carbon atoms, taken together, form a group-OCF2O-, -CF2CF2O - or-OCF2CF2O-;

each R6independently represents C1-C4alkyl, C2-C4alkenyl,2-C4quinil,3-C6cycloalkyl,1-C4halogenated,2-C4halogenoalkanes,2-C4halogenoalkanes,3-C6halogenosilanes, halogen, CN, NO2With1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4alkylamino,2-C8dialkylamino,3-C6cyclooctylamino,4-C8alkyl(cycloalkyl)amino, the 2-C4alkylsulphonyl,2-C6alkoxycarbonyl,2-C6alkylaminocarbonyl,3-C8dialkylaminoalkyl or3-C6trialkylsilyl;

R10represents H, C1-C4alkyl or C1-C4halogenated;

R11represents N or C1-C4alkyl and

n represents an integer from 1 to 4.

This invention relates to such a method, where the invertebrate pest or its habitat is in contact with a biologically effective amount of the compounds of formula I or a composition comprising the compound of formula I and a biologically effective amount of at least one additional compound or agent to suppress invertebrate pests.

This invention relates to the compound of formula Is, its N-oxides or salts

where is O or S;

J represents a phenyl ring, naftalina ring system, a 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring or ring system is optionally substituted(Oh) 1-4 R5;

R2is N; G; C1-C6alkyl, C2-C6alkenyl,2-C6quinil, 3-C6cycloalkyl, each of which is optionally substituted by one or more substituents selected from the group comprising halogen, G, CN, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C2-C6alkoxycarbonyl,2-C6alkylsulphonyl,3-C6trialkylsilyl; or phenyl, phenoxy or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R6; hydroxy; C1-C4alkoxy; C1-C4alkylamino; C2-C8dialkylamino; C3-C6cyclooctylamino; C2-C6alkoxycarbonyl and C2-C6alkylsulphonyl;

G represents a 5 - or 6-membered nonaromatic carbocyclic or heterocyclic ring, optionally incorporating one or two ring members, selected from the group consisting of C(=O), SO and S(O)2and optionally substituted by 1-4 substituents selected from R3;

each R3independently represents C1-C2alkyl, halogen, CN, NO2or1-C2alkoxy;

each R4independently represents H, C1-C6alkyl, C2-C6alkenyl,2 -C6quinil,3-C6cycloalkyl,1-C6halogenated,2-C6halogenoalkanes,2-C6halogenoalkanes,3-C6halogenosilanes, halogen, CN, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4allogenicity,1-C4halogenacetylenes,1-C4halogenallylacetic,1-C4alkylamino,2-C8dialkylamino,3-C6cyclooctylamino,2-C5alkoxyalkyl,1-C4hydroxyalkyl, C(O)R10, CO2R10C(O)NR10R11, NR10R11N(R11)CO2R10or3-C6trialkylsilyl or

each R4independently represents phenyl, benzyl, phenoxy or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R6;

each R5independently represents C1-C6alkyl, C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl,1-C6halogenated,2-C6halogenoalkanes,2-C6halogenoalkanes,3-C6halogenically is, halogen, CN, CO2H, CONH2, NO2, hydroxy, C1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4allogenicity,1-C4halogenacetylenes,1-C4halogenallylacetic,1-C4alkylamino,2-C8dialkylamino,3-C6cyclooctylamino,2-C6alkylsulphonyl,2-C6alkoxycarbonyl,2-C6alkylaminocarbonyl,3-C8dialkylaminoalkyl or3-C6trialkylsilyl or

each R5independently represents phenyl, benzyl, benzoyl, phenoxy, 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring optionally substituted with one to three substituents, independently selected from R6or

two groups of R5when they are attached to adjacent carbon atoms, taken together, form a group-OCF2O-, -CF2CF2O - or-OCF2CF2O-;

each R6independently represents C1-C4alkyl, C2-C4alkenyl,2-C4quinil,3-C6cycloalkyl,1-C4halogenated,2-C4g is loginuser, With2-C4halogenoalkanes,3-C6halogenosilanes, halogen, CN, NO2With1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4alkylamino,2-C8dialkylamino,3-C6cyclooctylamino,4-C8(alkyl)cyclooctylamino,2-C4alkylsulphonyl,2-C6alkoxycarbonyl,2-C6alkylaminocarbonyl,3-C8dialkylaminoalkyl or3-C6trialkylsilyl;

R10represents H, C1-C4alkyl or C1-C4halogenated;

R11represents N or C1-C4alkyl and

n represents an integer from 1 to 4.

This invention relates to compositions for combating invertebrate pest comprising a biologically effective amount of the compounds of formula I and at least one additional component selected from the group consisting of surfactants, solid and liquid diluents. This invention relates to such compositions, optionally additionally comprising an effective amount of at least one additional biologically active compound or agent.

In the above op is sanija the term "alkyl", used alone or in compound words such as "alkylthio" or "halogenated"includes alkyl straight or branched chain such as methyl, ethyl, n-propyl, isopropyl or the different butyl isomers, pentile or exile. The term "alkenyl includes alkenes with a straight or branched chain, such as 1-propenyl, 2-propenyl, and various isomers butenyl, pentenyl and hexenyl. The term "alkenyl also includes a polyene, such as 1,2-PROPADIENE and 2,4-hexadienyl. The term "quinil includes alkynes with a straight or branched chain, such as 1-PROPYNYL, 2-PROPYNYL, and the various isomers of butenyl, pentenyl and hexenyl. The term "quinil" may also include fragments containing several ternary relations, such as 2,5-hexadienyl. The term "alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropoxy and various isomers of butoxy, pentox, hexyloxy. The term "alkoxyalkyl" refers to alkoxysilane of alkyl. Examples of alkoxyalkyl include CH3OCH2CH3OCH2CH2CH3CH2OCH2CH3CH2CH2CH2OCH2and CH3CH2Och2CH2. The term "alkylthio" includes alkylthiophene straight or branched chain, such as methylthio, ethylthio, and various isomers of property, butylthio, pentylthio and hexylthio. The term "cyclol the l includes for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "trialkylsilyl" includes (CH3)3Si (CH3CH2)3Si and [(CH3)3C](CH3)2Si. The term "(alkyl)cycloalkenyl" refers to cycloalkylation, in which the hydrogen atom replaced by an alkyl radical; examples of such groups include methyl)cyclopropylamino, (ethyl)cyclobutylamine, (isopropyl)cyclopentylamine and (methyl)cyclohexylamino. As noted above in the brief description of the invention, cycloalkyl in cycloalkylation and (alkyl)cycloalkylation represents a C3-C6cycloalkyl, while the alkyl (alkyl)cycloalkylation represents a C1-C4alkyl.

The term "aromatic" means that all of the ring atoms is essentially lie in the same plane, havep-orbital perpendicular to the plane of the ring, and (4n+2) π-electrons, which, when n is 0 or takes a positive integer value associated with the ring to comply with hückel rule (Hückel''s rule). The term "aromatic ring system" refers to a fully unsaturated carbocycles and heterocycles in which at least one ring of a polycyclic ring system is aromatic. Aromatic carbocyclic ring or condensed carbocyclic who olavie systems include a fully aromatic carbocycle and carbocycle, in which at least one ring of a polycyclic ring system is aromatic (e.g. phenyl or naphthyl). The term "non-aromatic carbocyclic ring" refers to a fully saturated carbocycles, as well as partially or fully unsaturated carbocycles that do not meet the hückel rule. The term "hetero", referring to the rings or ring systems, means a ring or ring system in which at least one atom of the ring is carbon and which may contain from 1 to 4 heteroatoms, independently selected from the group consisting of nitrogen, oxygen and sulfur, provided that each ring contains no more than 4 nitrogen atoms, not more than 2 oxygen atoms and not more than 2 sulfur atoms. The term "heteroaromatic ring or ring system" and "aromatic condensed heterobicyclic ring system" includes fully aromatic heterocycles and heterocycles in which at least one ring of a polycyclic ring system is aromatic (where the term "aromatic" indicates that the hückel rule is executed). The term "non-aromatic heterocyclic ring or non-aromatic ring system" denotes fully saturated heterocycle, and a partially or fully unsaturated heterocycles, where any ring of the ring system does not meet the hückel rule. Heterocyclic ring or ring system may be attached through any available carbon atom or nitrogen by replacement of a hydrogen from a specified carbon atom or nitrogen.

The term "halogen"as used alone or in compound words such as "halogenated"means fluorine, chlorine, bromine or iodine. In addition, when used in compound words such as "halogenated"specified alkyl may be partially or completely replaced by halogen atoms that can be the same or different. Examples of "halogenation" include F3C, ClCH2, CF3CH2and CF3CCl2. The terms "halogenoalkanes", "halogenoalkanes", "halogenoalkane" and the like, are defined analogously to the term "halogenated". Examples of "halogenoalkane include (Cl)2C=CHCH2and CF3CH2CH=CHCH2. Examples of "halogenoalkane" include HC≡CCHCl, CF3C≡C, CCl3C≡C and FCH2C≡CH2. Examples of "halogenoalkane" include CF3O CCl3CH2O, HCF2CH2CHO and CF3CH2O.

Examples of "alkylcarboxylic" include C(O)CH3With(O)CH2CH2CH3and C(O)CH(CH3)2. Examples of "alkoxycarbonyl" include CH3OC(=O), CH3CH2OC(=O), CH3CH2CH2OS(=O), (CH3)2CHOC(=O) and the various isomers of butoxy or phenoxycarbonyl the and. Examples of "alkylaminocarbonyl" include CH3NHC(=O), CH3CH2NHC(=O), CH3CH2CH2NHC(=O) (CH3)2CHNHC(=O)and the various isomers of butylamino or intramyocardial. Examples of "dialkylaminoalkyl include (CH3)2NC(=O) (CH3CH2)2NC(=O), CH3CH2(CH3)NC(=O), CH3CH2CH2(CH3)NC(=O) and (CH3)2CHN(CH3)C(=O).

The total number of carbon atoms in the group substituent shown by the prefix "Ci-Cj"where i and j are integers from 1 to 8. For example, "C1-C4alkylsulfonyl" means a group of methylsulfonyl to butylsulfonyl; "C2alkoxyalkyl represents CH3Och2; "C3alkoxyalkyl" means, for example, CH3CH(OCH3), CH3Och2CH2or CH3CH2Och2; "C4alkoxyalkyl" refers to the various isomers of an alkyl group, substituted alkoxygroup and containing four carbon atoms, and examples of such alkyl groups include CH3CH2CH2Och2and CH3CH2Och2CH2. In the above description, when the compound of formula I includes a heterocyclic ring, all the substituents attached to the ring via any available carbon atom or nitrogen by replacement of an atom of water is kind of the specified carbon atom or nitrogen.

When the connection is replaced by a Deputy with the specified subscript, which indicates that the number of these substituents can exceed 1, the said substituents (when they exceed 1) are independently selected from the group of defined substituents. In addition, when the lower index indicates a certain interval, for example (R)i-jthen the number of substituents can be selected in the interval of integers from i to j, inclusive.

The term "optionally substituted" indicates that the fragment can be substituted or unsubstituted. The term "optionally substituted one to three substituents", etc. indicates that the fragment can be unsubstituted or one to three of the available positions on the fragment can be substituted. When the fragment contains a Deputy, which can be hydrogen, for example, R4when the Deputy represents hydrogen, this is equivalent to the fact that the specified portion is unsubstituted.

The compounds of formula I can exist as one or more stereoisomers. Different stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. Of particular interest are geometric isomers, in which R2imioramine can be insynoranti-position relative to B, or a mixture of - andanti-geometric isomers. A qualified specialist in this field it is clear that one stereoisomer may be more active and/or may exhibit beneficial effects when more content relative to another(their) stereoisomer(s) or when separated from the other(s) stereoisomer(s). In addition, a qualified specialist knows how to separate, enrich, and/or to selectively receive said stereoisomers. Accordingly, the compounds of formula I may also be present in the form of a mixture of stereoisomers, individual stereoisomers or in the form of optically active forms. Some compounds of formula I may also exist in the form of one or more tautomers, and all tautomeric forms of these compounds are part of this invention. Additionally, the compounds of this invention may be present as a mixture of tautomers, or individual tautomers.

This invention includes compounds selected from compounds of the formula I, their N-oxides and salts. A qualified specialist in this field it is clear that not all nitrogen-containing heterocycles can form N-oxides as nitrogen must be available only pair of electrons for oxidation in the oxide; a qualified professional can also determine the nitrogen-containing heterocycles, which can brazability N-oxides. A qualified specialist in this field will also be obvious that tertiary amines can form N-oxides. Synthetic methods for obtaining the N-oxides of heterocycles and tertiary amines are well known qualified, including the oxidation of heterocycles and tertiary amines with nagkakamali, such as peracetic and m-chlormadinone acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as tert-butylhydroperoxide, perborate sodium and dioxirane, such as dimethyldioxirane. Such methods of obtaining N-oxides described in detail and discussed in the literature, for example in the following publications: T.L. Gilchrist, inComprehensive Organic SynthesisVol.7pp. 748-750, S.V. Ley, Ed., Pergamon Press; M. Tišler and B. Stanovnik, inComprehensive Heterocyclic ChemistryVol.3pp. 18-19, A.J. Boulton and A. McKillop, Eds., Pergamon Press; M.R. Grimmett and B.R.T. Keene, inAdvances in Heterocyclic ChemistryVol.43pp. 139-151, A.R. Katritzky, Ed., Academic Press; M. Tišler and B. Stanovnik, inAdvances in Heterocyclic ChemistryVol.9pp. 285-291, A.R. Katritzky and A.J. Boulton, Eds., Academic Press; and G.W.H. Cheeseman and E.S.G. Werstiuk, inAdvances in Heterocyclic ChemistryVol.22pp. 390-392, A.R. Katritzky and A.J. Boulton, Eds., Academic Press.

Salts of the compounds of this invention include the salts of joining inorganic or organic acids, such as Hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, xalilov, propional what I salicylic, tartaric, 4-toluensulfonate or valeric acid. Salts of the compounds of this invention also include salts of organic bases (e.g. pyridine, ammonia, or triethylamine) or inorganic bases (e.g., hydrides, hydroxides or carbonates of sodium, potassium, lithium, calcium, magnesium or barium)when the compound contains an acid fragment, such as a carboxylic acid group or a phenol group.

As mentioned above, J represents phenyl ring, naftalina ring system, a 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring or ring system is optionally substituted by 1-4 R5. The term "optionally substituted"relating to J groups means groups which are unsubstituted or have at least one Deputy, other than hydrogen, which does not reduce the biological activity characteristic of the unsubstituted analog. Example phenyl, optionally substituted by 1-4 R5is the ring illustrated as U-1 in figure 1, where Rvis R5and r represents an integer from 0 to 4. Example naftilos group, optionally substituted by 1-4 R5is the group shown as U-85 on the Image 1, where Rvpredstavljaet R 5and r represents an integer from 0 to 4. Examples of 5 - or 6-membered heteroaromatic ring, optionally substituted by 1-4 R5include the rings U-2)-(U-53), shown in figure 1, where Rvis R5and r represents an integer from 0 to 4. You should pay attention to the fact that (J-1)-(J-5), below, also refer to the 5 - or 6-membered heteroaromatic rings. Moreover, (U-2)-(U-20) are examples of J-1 (U-21)-(U-35) and U-40 are examples of J-2, (U-36)-(U-39) are examples of J-3, (U-41)-(U-48) are examples of J-4 and U-49)-(U-53) are examples of J-5. Examples of aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring systems, optionally substituted by 1-4 R5include (U-54)-(U-84), shown in figure 1, where Rvis R5and r represents an integer from 0 to 4.

The nitrogen atoms that require substitution to fill their valence, substituted N, or Rv. You should pay attention to the fact that some groups U can be replaced in less than 4 groups of Rv(for example, U-14, U-15, U-18)-(U-21) and (U-32)-(U-43) can be replaced by only one Rv). You should also note that when the attachment point (RV)rand U is depicted as floating, (RV)rcan be attached to any available carbon atom of the group U. Schedulability attention to the fact, that when the attachment point U is depicted as floating, the group U may be attached to the remainder of formulae I through any available carbon atom of the group U by replacing a hydrogen atom.

Image 1

As noted above, G represents a 5 - or 6-membered nonaromatic carbocyclic or heterocyclic ring, optionally incorporating one or two ring members, selected from the group consisting of C(=O), SO and S(O)2and optionally substituted by 1-4 substituents selected from R3. Examples of such include groups G group, p is defined as (G-1)-(G-41) on the image 2, where m is an integer from 0 to 4. The term "optionally substituted"groups G means group, which are unsubstituted or have at least one Deputy, other than hydrogen, which does not reduce the biological activity characteristic of the unsubstituted analog. You should also note that when the attachment point of G is depicted as floating, the group G may be attached to the remainder of formulae I through any available carbon atom of the group U by replacing a hydrogen atom. Optional substituents may be attached to any available carbon atom or nitrogen by replacement of a hydrogen atom. You should also pay attention to the fact that when G includes a ring selected from (G-24)-(G-29) and (G-32)-(G35), And selected from O, S or NR3. In addition, when G is G-3, G-5, G-7, G-9, G-16)-(G-18), G-23, G-24)-(G-29) and (G-32)-(G35) (when a is NR3), the nitrogen atoms that require substitution to fill their valence, substituted N, or R3.

Image 2

As discussed the axis above some groups of R1and R2may be optionally substituted by one or more substituents. The term "optionally substituted"relating to these groups, means R1and/or R2groups that are unsubstituted or have at least one Deputy, other than hydrogen. Examples of the optionally substituted R1and/or R2groups are groups which may be optionally substituted by replacement of a hydrogen atom from a carbon atom, R1and/or R2group one or more (the number of substituents may equal the total number of hydrogen atoms that can be replaced at any given R1and/or R2the group substituents, optionally selected from the substituents listed above in the brief description of the invention. Although these alternates are listed, it should be noted that there is no need for their presence, since they are optional substituents. Interest group, R1and/or R2which are unsubstituted. Interest group, R1and/or R2substituted by one to five substituents. Also of interest groups, R1and/or R2substituted by one Deputy.

As noted above, each of R1and R2can independently (CreditWatch) to submit With 1-C6alkyl, C2-C6alkenyl,2-C6quinil or3-C6cycloalkyl, each independently substituted by one or more substituents selected from (among others) phenyl, phenoxy or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R6. The term "optionally substituted"relating to these groups means groups which are unsubstituted or have at least one Deputy, other than hydrogen, which does not reduce the biological activity characteristic of the unsubstituted analog. Examples of such substituents include the rings represented as (U-1)-(U-53) and U-88 in figure 1, with the exception of rings, which optionally is substituted by 1-3 substituents, independently selected from R6and not (Rv)r. You should pay attention to the fact that there is no need for the presence of the substituents R6since they are optional substituents.

As noted above, each R4independently represents (among others) phenyl, benzyl, phenoxy or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R6. The term "optional someseni the", related to data R4groups means groups which are unsubstituted or have at least one Deputy, other than hydrogen, which does not reduce the biological activity characteristic of the unsubstituted analog. Examples of such R4groups include rings represented as (U-1)-(U-53, U-86 and U-88, are presented in figure 1, with the exception of such rings, which optionally is substituted by 1-3 substituents, independently selected from R6and not (Rv)r. You should pay attention to the fact that there is no need for the presence of the substituents R6since they are optional substituents.

As noted above, each R5independently represents (among others) phenyl, benzyl, benzoyl, phenoxy, 5 - or 6-membered heteroaromatic ring or an aromatic 8-, 9 - or 10-membered condensed heterobicyclic ring system, each ring or ring system optionally substituted with one to three substituents, independently selected from R6. Examples of such groups R5include rings and ring systems represented as (U-1)-(U-88) on the image 1, with the exception of rings and ring systems are optionally substituted by 1-3 substituents, independently selected from R6and not (Rv)r. It is necessary to pay attention to detail is e, it is not necessary in the presence of the substituents R6since they are optional substituents.

Preferred from the standpoint of cost, ease of synthesis or application and/or biological effectiveness are the following.

1. Ways, including the compounds of formula I, where

R2represents H; C1-C6alkyl, C2-C6alkenyl,2-C6quinil or3-C6cycloalkyl, each of which is optionally substituted by one or more substituents selected from the group consisting of halogen, CN, C1-C2alkoxy, C1-C2alkylthio,1-C2alkylsulfonyl and C1-C2alkylsulfonyl;

one R4attached to the phenyl ring in position 2 or in position 5, and the specified R4is1-C4alkyl, C1-C4halogenated, halogen, CN, NO2With1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4allogenicity,1-C4halogenacetylenes or1-C4halogenallylacetic;

n is 1 or 2.

2. Methods of paragraph 1, where J represents a phenyl group optionally substituted by 1-4 R5.

3. Methods of paragraph 2, where the

In is About, and

each R5independently is halogen, C1-C4alkyl, C1-C2alkoxy, C1-C4halogenated, CN, NO2With1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4allogenicity,1-C4halogenacetylenes,1-C4halogenallylacetic or2-C4alkoxycarbonyl, or

each R5independently represents phenyl or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R6or

two R5groups, when attached to adjacent carbon atoms, together form a group-OCF2O-, -CF2CF2O - or-OCF2CF2O-.

4. Methods of paragraph 3, where

R2is1-C4alkyl, optionally substituted with halogen, CN, OCH3or S(O)pCH3;

one R4attached to the phenyl ring in position 2 and the specified R4is CH3, CF3, OCF3, OCHF2, S(O)pCF3, S(O)pCHF2, CN or halogen;

the second R4represents H, F, Cl, Br, I, CN or CF3;

each R5independently represents halogen, methyl, CF3, OCF3, OHF 2, S(O)pCF3, S(O)pCHF2, OCH2CF3, OCF2CHF2, S(O)pCH2CF3or S(O)pCF2CHF2; phenyl, pyrazol, imidazole, triazole, pyridine or pyrimidine ring and each ring optionally substituted with one to three substituents, independently selected from C1-C4of alkyl, C1-C4halogenoalkane, halogen and CN;

p is 0, 1 or 2.

5. Ways to paragraph 4, where R2represents H, Me, Et, isopropyl or tert-butyl.

6. Methods of paragraph 1, where

J represents a 5 - or 6-membered heteroaromatic ring selected from the group consisting of J-1, J-2, J-3, J-4 and J-5, and each J is optionally substituted by 1-3 R5

Q represents O, S, NH or NR5;

W, X, Y and Z independently represent N, CH or CR5provided that in J-4 and J-5, at least one of W, X, Y or Z is N.

7. Methods of paragraph 6, where

In is On and

each R5independently represents C1-C4alkyl, C1-C4halogenated, halogen, CN, NO2With1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4allogenicity,1-C4halogenacetylenes,1-C4halogenates hanil or 2-C4alkoxycarbonyl; or phenyl or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R6.

8. The method of paragraph 7, where

J is substituted by 1-3 R5selected from the group consisting of J-6, J-7, J-8, J-9, J-10, J-11, J-12 and J-13

V represents N, CH, CF, CCl, CBr or CI;

each R6aindependently represents H or R6;

R6is1-C6alkyl, C3-C6cycloalkyl,1-C6halogenated, halogen, CN, C1-C4alkoxy, C1-C4halogenoalkane or1-C4allogenicity;

each R7independently represents C1-C6alkyl, C1-C6halogenated, halogen, CN, C1-C4alkoxy, C1-C4halogenoalkane or1-C4allogenicity;

R9is2-C6alkyl, C1-C6halogenated,3-C6alkenyl,3-C6halogenoalkanes,3-C6quinil or3-C6halogenoalkanes;

R10is1-C4alkyl or C1-C4halogenated;

R11is1-C4alkyl and

n is 1 or 2.

You should pay attention to who and what what R7and R9is the subset of R5. In addition, the atoms of F, Cl, Br or I, are included in the values of V are a subset of R6. Interesting are the ways in paragraph 8, where V is N. Interest are also ways to paragraph 8, where V is CH, CF, CCl or CBr. Especially of interest ways to paragraph 8, where V represents N or CH.

9. Ways to paragraph 8, where

R2is1-C4alkyl, optionally substituted with halogen, CN, OCH3or S(O)pCH3; or CH2With≡SN;

one R4attached to the phenyl ring in position 2 and the specified R4is CH3, CF3, OCF3, OCHF2, S(O)pCF3, S(O)pCHF2, CN or halogen;

the second R4represents H, F, Cl, Br, I, CN or CF3;

R6arepresents H, C1-C4alkyl, C1-C4halogenated, halogen or CN;

R7is CH3, CF3, OCH2CF3, OCHF2or halogen;

R9is CH2CF3, CHF2or CF3and

p is 0, 1 or 2.

Interesting are the ways to paragraph 9, where one group R4attached to the phenyl ring in position 2 and the specified R4is CH3, Cl or Br, and the second R4represents H, F, Cl, Br, I, CN or CF3.

10. Ways to paragraph 9, where the J, substituted by 1-3 R5is J-6; V is N or CH and R7is CH3, CF3, OCH2CF3, OCHF2or halogen.

11. Methods of paragraph 10, where R6arepresents F, Cl or Br and R7represents halogen or CF3.

12. Ways to paragraph 9, where J is substituted by 1-3 R5is the J-7 and R9is2-C6alkyl or C1-C6halogenated.

Interest methods of paragraph 12, where V represents N or CH; R6arepresents Cl or Br and R9is CF3, CHF2CH2CF3, CF2CHF2.

13. Ways to paragraph 9, where J is substituted by 1-3 R5is J-8; V is N; R6arepresents Cl or Br and R7represents halogen or CF3.

14. Ways to paragraph 9, where J is substituted by 1-3 R5is J-9; R6arepresents Cl or Br and R7is CF3.

15. Ways to paragraph 9, where J is substituted by 1-3 R5is J-10; R6arepresents Cl or Br and R9is CH2CF3, CHF2or CF3.

16. Ways to paragraph 9, where J is substituted by 1-3 R5is J-11; R6arepresents Cl or Br and R7represents halogen, OCH2CF3, OCHF2or CF3.

17. Ways to paragraph 9, where J is substituted by 1-3 R5is J-12; R6athe submitted is Cl or Br; R7represents halogen, OCH2CF3, OCHF2or CF3and R9is CH2CF3, CHF2or CF3.

18. Ways to paragraph 9, where J is substituted by 1-3 R5is J-13; R6arepresents Cl or Br and R9is CH2CF3, CHF2or CF3.

Particularly preferred methods are methods comprising compounds selected from the following groups:

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-ilidene]methanamine,

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-ilidene]ethanamine,

N-[6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]methanamine,

N-[6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]ethanamine,

N-[6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]methanamine,

N-[6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin the-4-ilidene]ethanamine,

N-[6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-methyl-2-propanamine,

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-methyl-2-propanamine,

N-[2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine and

N-[2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-methyl-2-propanamine.

Preferred also are the following.

19. Methods of paragraph 1, where

In represents NR1;

J is substituted by 1-3 R5is J-6 (as defined above in paragraph 8);

each R1independently represents C1-C6alkyl;

R2represents N or C1-C6alkyl or

R1and R2taken together form a linking chain, consisting of 2-5 members containing at least one carbon member, optionally including not more than two carbon members of the form C(=O), and optionally one member selected from the atoms of nitrogen and oxygen and optionally substituted by 1-4 substituents selected from R3;

each R3independently represents C1-C2alkyl, halogen, CN, NO2or1-C2alkoxy; one of R4/sup> attached to the phenyl ring in position 2 and the specified R4is CH3, Cl or Br, and the second R4represents H, F, Cl, Br, I or CF3.

Of interest also ways including connection of paragraph 19, where R1and R2taken together, may form a linking chain selected from the group consisting of-CH2CH2-, -CH2CH2CH2-, -CH2CH2C(=O)-, -CH=C(CH3)-, -C(CH3)=CH - and-CH=N-, so that the left end of the segment is attached at the location of R1and the right end of the segment is attached at the location of R2.

Especially preferred is the method of paragraph 19, including a connection

7,9-dichloro-5-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-2,5-dihydroimidazo[1,2-c]hinzelin.

This invention relates also to compositions for combating invertebrate pest comprising a biologically effective amount of compounds of formula I. the Preferred compositions are compositions that include the compounds described in paragraphs 1-19 listed above in a particularly preferred methods.

Preferred compounds according to the ease of synthesis and/or biological effectiveness are the following.

A. the compounds of formula I, where

In is About;

R2represents N or C1-the 6alkyl, C2-C6alkenyl,2-C6quinil or3-C6cycloalkyl, each of which is optionally substituted by one or more substituents selected from the group consisting of halogen, CN, C1-C2alkoxy, C1-C2alkylthio,1-C2alkylsulfonyl and C1-C2alkylsulfonyl;

one group R4attached to the phenyl ring in position 2 or in position 5 and specified R4is1-C4alkyl, C1-C4halogenated, halogen, CN, NO2C1-C4alkoxy, C1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4allogenicity,1-C4halogenacetylenes or1-Halogenallylacetic;

each R5independently is halogen, C1-C4alkyl, C1-C2alkoxy, C1-C4halogenated, CN, NO2With1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4allogenicity,1-C4halogenacetylenes,1-C4halogenallylacetic or2-C4alkoxycarbonyl or

each R5independently represents f the Nile or 5 - or 6-membered heteroaromatic ring, moreover, each ring optionally substituted with one to three substituents, independently selected from R6or

two groups of R5when attached to adjacent carbon atoms, taken place, form a group-OCF2O-, -CF2CF2O - or-OCF2CF2O-and

n is 1 or 2.

C. Connections And where

J represents a phenyl group optionally substituted by 1-4 R5;

R2is1-C4alkyl, optionally substituted with halogen, CN, OCH3or S(O)pCH3;

one R4attached to the phenyl ring in position 2 and the specified R4is CH3, CF3, OCF3, OCHF2, S(O)pCF3, S(O)pCHF2, CN or halogen;

the second R4represents H, F, Cl, Br, I or CF3;

each R5independently represents halogen, methyl, CF3, OCF3, OCHF2, S(O)pCF3, S(O)pCHF2, OCH2CF3, OCF2CHF2, S(O)pCH2CF3or S(O)pCF2CHF2; or phenyl, pyrazol, imidazole, triazole, pyridine or pyrimidine ring, each ring optionally substituted with one to three substituents, independently selected from C1-C4of alkyl, C1-C4halogenoalkane, halogen and CN, and

p is 0, 1 or 2.

C. Connections, where R2predstavljaet N, Me, Et, isopropyl or tert-butyl.

D. Connections And where

J represents a 5 - or 6-membered heteroaromatic ring selected from the group consisting of J-1, J-2, J-3, J-4 and J-5, and each J is optionally substituted by 1-3 R5

Q represents O, S, NH or NR5;

W, X, Y and Z independently represent N, CH or CR5provided that in J-5 and J-5, at least one of W, X, Y or Z is N and

each R5independently represents C1-C4alkyl, C1-C4halogenated, halogen, CN, NO2With1-C4halogenoalkane,1-C4alkylthio,1-C4alkylsulfonyl,1-C4alkylsulfonyl, C1-C4allogenicity,1-C4halogenacetylenes,1-C4halogenallylacetic or2-C4alkoxycarbonyl; phenyl or 5 - or 6-membered heteroaromatic ring, each ring optionally substituted with one to three substituents, independently selected from R6.

That is, the Connection D, where

J is substituted by 1-3 R5selected from the group consisting of J-6, J-7, J-8, J-9, J-10, J-11, J-12 and J-13

V represents N, CH, CF, CCl, CBr or CI;

each R6aindependently represents H or R6;

R6is1-C63-C6cycloalkyl,1-C6halogenated, halogen, CN, C1-C4alkoxy, C1-C4halogenoalkane or1-C4allogenicity;

each R7independently represents C1-C6alkyl, C1-C6halogenated, halogen, CN, C1-C4alkoxy, C1-C4halogenoalkane or1-C4allogenicity;

R9is2-C6alkyl, C1-C6halogenated,3-C6alkenyl,3-C6halogenoalkanes,3-C6quinil or3-C6halogenoalkanes;

R10is1-C4alkyl or C1-C4halogenated;

R11is1-C4alkyl and

n is 1 or 2.

You should pay attention to the fact that R7and R9represent a subset of R5. You should pay attention to the fact that the atoms of F, Cl, Br or I, are included in the values of V are a subset of R6. Interest compounds E, where V is N. of interest connections, E, where V is CH, CF, CCl or CBr. Especially of interest connection E, where V represents N or CH.

F. Connection E, where

R2is1-C4alkyl, optionally substituted with halogen, CN, OCH3or S(O)pCH3Ilin 2With≡SN;

one R4attached to the phenyl ring in position 2 and the specified R4is CH3, CF3, OCF3, OCHF2, S(O)pCF3, S(O)pCHF2, CN or halogen;

the second R4represents H, F, Cl, Br, I or CF3;

R6arepresents H, C1-C4alkyl, C1-C4halogenated, halogen or CN;

R7is CH3, CF3, OCH2CF3, OCHF2or halogen;

R9is CH2CF3, CHF2or CF3and

p is 0, 1 or 2.

Interest compounds of F, where one of R4attached to the phenyl ring in position 2 and the specified R4is CH3, Cl or Br, and the second R4represents H, F, Cl, Br, I or CF3.

G. compounds of F, where J is substituted by 1-3 R5is J-6; V is N or CH and R7is CH3, CF3, OCH2CF3, OCHF2or halogen.

N. Connection G, where R6arepresents F, Cl or Br and R7represents halogen or CF3.

I. compounds of F, where J is substituted by 1-3 R5is the J-7 and R9is2-C6alkyl or C1-C6halogenated.

Interest compounds I, where V represents N or CH; R6arepresents Cl or Br and R9is CF3, CHF2 CH2CF3, CF2CHF2.

J. compounds of F, where J is substituted by 1-3 R5is J-8; V is N; R6arepresents Cl or Br and R7represents halogen or CF3.

K. compounds of F, where J is substituted by 1-3 R5is J-9; R6arepresents Cl or Br and R7is CF3.

L. Connections F, where J is substituted by 1-3 R5is J-10; R6arepresents Cl or Br and R9is CH2CF3, CHF2or CF3.

M Connection F, where J is substituted by 1-3 R5is J-11; R6arepresents Cl or Br and R7represents halogen, OCH2CF3, OCHF2or CF3.

N. Connection F, where J is substituted by 1-3 R5is J-12; R6arepresents Cl or Br; R7represents halogen, OCH2CF3, OCHF2or CF3and R9is CH2CF3, CHF2or CF3.

O. compounds of F, where J is substituted by 1-3 R5is J-13; R6arepresents Cl or Br and R9is CH2CF3, CHF2or CF3.

Especially preferred are compounds selected from the group including

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-ilidene]methanamine,

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin the-4-ilidene]-2-propanamine,

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-ilidene]ethanamine,

N-[6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]methanamine,

N-[6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]ethanamine,

N-[6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]methanamine,

N-[6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]ethanamine,

N-[6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-methyl-2-propanamine,

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-methyl-2-propanamine,

N-[2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine and

N-[2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-methyl-2-propanamine.

Interest compounds of formula I, where

In represents NR 1;

J is substituted by 1-3 R5is J-6 (as defined above in paragraph 8);

each R1independently represents C1-C6alkyl;

R2represents N or C1-C6alkyl or

R1and R2taken together form a linking chain of 2-5 members, including at least one carbon member, optionally including not more than two carbon members of the form C(=O) and optionally one additional member selected from nitrogen and oxygen, optionally substituted by 1-4 substituents selected from R3;

each R3independently represents C1-C2alkyl, halogen, CN, NO2or1-C2alkoxy; one of R4attached to the phenyl ring in position 2 and the specified R4is CH3, Cl or Br, and the second R4represents H, F, Cl, Br, I or CF3.

Of interest are also compounds in which in formula I R1and R2taken together, may form a linking chain selected from the group consisting of-CH2CH2-, -CH2CH2CH2-, -CH2CH2C(=O)-, -CH=C(CH3)-, -C(CH3)=CH - and-CH=N-, so that the left end of the segment is attached at the location of R1and the right end of the segment is attached at the location of R2.

Especially, it is preferable to connect the imposition of 7,9-dichloro-5-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-2,3-dihydroimidazo[1,2-c]hinzelin.

To obtain the compounds of formula I can be used one or more methods presented below in schemes 1-35, and their different ways. Values In a, J, V, R1-R6and n in the compounds of formulas I, II and 2-96 below correspond to the values defined above in the brief description of the invention. Compounds of formulas Ia-f, IIa-c, 3a, 4a-t, 10a, 18a, 19a-c and 20A are various subsets of the compounds of formulas I, II, 3, 4, 10, 18, 19 and 20, respectively.

The compounds of formula Ia or Ib (compounds of formula I, where a represents O or S, respectively) can be obtained from compounds of formula IIa or formula IIb, respectively, by cyclization in the presence of dehydrating agents, such as POCl3, POCl3/PCl5, SOCl2or oxalicacid. This cyclization is usually carried out in solvents, such as dichloroethane, dichloromethane, chloroform, benzene, toluene, xylenes, hexane, cyclohexane, 1,4-dioxane, tetrahydrofuran and chlorobenzene, at a temperature in the range from 0°C to the temperature of reflux distilled mixture. Alternative cyclodehydration can be carried out by treating compound of formula IIa or formula IIb with triphenylphosphine and bromine or iodine, optionally in the presence of tertiary amine bases, such as triethylamine or diisopropylethylamine. Typical examples of such techniques, see Monatsh. Shem.1989, 120, 973-980, andJ. Org. Chem.200 , 65, 1022-1030.

Scheme 1

The combination of the amine of formula 2 with an acid chloride of the acid of formula 3 in the presence of acid acceptor may result in the compounds of formula IIa (scheme 2). Conventional acid acceptors are amine base, such as triethylamine, diisopropylethylamine and pyridine; other acid acceptors include hydroxides such as sodium hydroxide and potassium hydroxide, and carbonates such as sodium carbonate and potassium carbonate. Some examples of useful acid acceptors deposited on polymers, for example, associated with the polymer diisopropylethylamine and associated with the polymer dimethylaminopyridine. The combination can be carried out in a suitable inert solvent such as tetrahydrofuran, dioxane, diethyl ether or dichloromethane, getting anilide formula IIa.

At a later stage amides of formula IIa can be converted to thioamides of formula IIb using standard reagents transfer tigraphy, including pentasulfide phosphorus and reagent Lawesson (Lawesson''s reagent).

Scheme 2

An alternative method of preparing compounds of formula IIa includes the combination of an amine of formula 2 with an acid of formula 4 in the presence of a dehydrating agent, such as dicyclohexylcarbodiimide (DCC), 1,1'-carbonelli midazol, the acid chloride of bis(2-oxo-3-oxazolidinyl)phosphinic acid or hexaphosphate benzotriazol-1 yloxy-Tris(dimethylamino)phosphonium (scheme 3). Reagents deposited on the polymer, such as polimerobetonie cyclohexylcarbodiimide, are also useful in this synthesis. The reaction mix can be carried out in a suitable inert solvent such as dichloromethane or N,N-dimethylformamide. Methods of synthesis, are presented on figures 2 and 3, are only typical examples of useful methods for obtaining compounds of formula II, as the literature describes a large number of ways to implement reactions of this type.

Scheme 3

A qualified specialist in this field it is clear that the acid chlorides of formula 3 can be obtained from the acids of formula 4 by a variety of well known ways. For example, the acid chlorides of formula 3 is easily derived from carboxylic acids of formula 4 by the interaction of the carboxylic acid 4 with thionyl chloride or oxalylamino in an inert solvent, such as toluene or dichloromethane, in the presence of catalytic amounts of N,N-dimethylformamide.

Amines of the formula 2 can usually be obtained from the corresponding 2-nitrobenzamide formula 5 by the catalytic hydrogenation of the nitro group (scheme 4). Typical techniques include the recovery in what oredom in the presence of a metal catalyst, such as palladium on carbon or platinum oxide, hydroxyl solvents, such as ethanol and isopropanol. They can also be obtained by reduction with zinc in acetic acid. These techniques are well described in the chemical literature.

Scheme 4

Intermediate 2-nitrobenzamide formula 5 is easily obtained from commercially available 2-nitrobenzoic acids (scheme 5). There can be used conventional methods for producing amides. Typical examples of such methods include direct dehydrative the combination of acids of formula 6 with amines of formula 7 using, for example, DDC, turning acids in activated form, such as acid chlorides or anhydrides, and the subsequent combination with amines to form amides of the formula 5. Alkylaromatic, such as ethylchloride or isopropylcarbamate are particularly useful reagents for reactions of this type, including the activation of acid. In the chemical literature, the methods of obtaining the amides is described.

Scheme 5

Intermediate Anthranilic acid amides of the formula 2 can also be derived from anhydrides of N-carboxyanhydrides acid of formula 8, as shown in scheme 6. Typical methods involve the combination of equimolar amounts of amine 7 with any the reed N-carboxyanhydrides acid in a polar aprotic solvent, such as pyridine and N,N-dimethylformamide, at a temperature in the range from room temperature to 100°C. the Anhydride of N-carboxyanhydrides acid of formula 8 may be obtained by methods described in the publication Coppola,Synthesis1980, 505-36.

Scheme 6

As shown in scheme 7, an alternative method of preparing compounds of formula IIa involves reacting an amine of formula 7 with benzoxazinones formula 10. The reaction is presented in figure 7, can be carried out without solvent or in a variety of suitable solvents including tetrahydrofuran, diethyl ether, pyridine, dichloromethane or chloroform with optimum temperatures in the range from room temperature to the temperature of reflux distilled solvent. The usual reaction benzoxazinones with amines to obtain anthranilamide well described in the chemical literature. Chemical properties benzoxazinones see Jakobsen et al.,Biorganic and Medicinal Chemistry2000, 8, 2095-2103, and there in the links. Cm. publication Coppola,J. Heterocyclic Chemistry1999, 36, 563-588.

Scheme 7

Benzoxazinone formula 10 can be obtained by using different methods. Two techniques that are particularly useful are presented in detail in schemes 8 and 9. In scheme 8 benzoxazine formula 10 obtained directly combination is the use of carboxylic acid of formula 4 with an Anthranilic acid of formula 11. This technique involves the sequential addition of methanesulfonanilide to the carboxylic acid of formula 4 in the presence of an amine base such as triethylamine or pyridine, followed by the addition of Anthranilic acid of formula 11, followed by a second addition of triethylamine and methanesulfonanilide. This practice usually leads to a good output benzoxazinone and is particularly useful for producing compounds of formula 10A of pyrazolylborate acids of formula 4A.

Scheme 8

Figure 9 presents an alternative way of obtaining benzoxazinones formulas 10 and 10A, which includes a combination of acid chloride of formula 3 with the anhydride of N-carboxyanhydrides acid of formula 8 to obtain directly benzoxazinone formula 10. The compounds of formula 10A can be obtained from the acid chloride pyrazolones acid of formula 3A on the same methodology. For this reaction are suitable solvent, such as pyridine or pyridine/acetonitrile. The acid chlorides of formula 3A can be obtained from the corresponding acids of formula 4A with known methods, such as chlorination with thionyl chloride or oxalylamino.

Scheme 9

Getting anhydride N-carboxyanhydrides acid of formula 8 may be made from tinov formula 13, as shown in scheme 10. Satiny formula 13 can be obtained from the aniline derivatives of formula 12 as described in the literature methods. Oxidation of isatin 13 hydrogen peroxide usually leads to good outputs corresponding anhydride N-carboxyanhydrides acid 8 (Angew. Chem. Int. Ed. Engl.1980, 19, 222-223). Anhydrides of N-carboxyanhydrides acid can also be derived from Anthranilic acid 11 with the help of many known methods, including the interaction of the compound (11) with phosgene or an equivalent of phosgene.

Scheme 10

The compounds of formula Ic or Id (the compounds of formula I in which b is NR1) can be obtained from anthranilamide formula 14 by cyclization with amidol formula 15 in the presence of dehydrating agents, such as POCl3, POCl3/PCl5or SOCl2(scheme 11). The cyclization is usually carried out in solvents, such as dichloroethane, dichloromethane, chloroform, benzene, toluene, xylenes, hexane, cyclohexane, 1,4-dioxane, tetrahydrofuran and chlorobenzene, at temperatures between 0°C to the temperature of reflux distilled mixture. The compounds of formula Ic (where R2is H) can be treated with electrophiles of formula 16 (where Lg is a leaving group such as halogen and alkyl - or arylsulfonate), optional what about in the presence of an acid acceptor, obtaining compounds of formula Id (where R2is not H). Conventional acid acceptors include amine bases such as triethylamine, diisopropylethylamine and pyridine; other acid acceptors include hydroxides such as sodium hydroxide and potassium hydroxide, and carbonates such as sodium carbonate and potassium carbonate. Some examples of useful acid acceptors deposited on polymers, such as polimerobetonie diisopropylethylamine and polimerobetonie dimethylaminopyridine. Such reactions are usually carried out in solvents, such as dichloroethane, dichloromethane, chloroform, benzene, toluene, xylenes, hexane, cyclohexane, 1,4-dioxane, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide and chlorobenzene, at temperatures between 0°C to the temperature of reflux distilled mixture. The compounds of formula Id can be obtained from compounds of formula 14 and 15 (where R1is H) using similar techniques. Alkylation of compounds of formula Id alkylating agent with two leaving groups (for example, ethylenedibromide or Propylenediamine) provides for obtaining the compounds of formula Ie, where, for example, a fragment of R1-R2represents CH2CH2or CH2CH2CH2.

Scheme 11

Connect four is uly 14 are well known and are commercially available or can be obtained by known methods. Amides of formula 15 can be obtained from the acids of formula 4 or acid chlorides of formula 3 interaction with amines of the formula R1NH2in accordance with the methods presented in schemes 2, 3 and 5.

As shown in scheme 11, compounds of formula If can also be obtained by dehydration of compounds of formula IIc. The compounds of formula IIc can be obtained from anilines with heterocycle at the ortho-position containing fragment NH (formula 16), and compounds of formula 3 in the presence of an acid acceptor in accordance with the methods described in scheme 2. In some examples, the dehydration IIc can be implemented in combination with direct obtaining the compounds of formula If. A detailed description of this sequence of reactions shown in example 3.

Scheme 11a

Benzoic acid of formula 4, where J represents optionally substituted phenyl ring, are well known in the art and are commercially available or can be obtained in accordance with well known techniques. Heterocyclic acids of formula 4, where J represents optionally substituted heterocycle, can be obtained according to the methods presented in the diagrams 12-35. General and specific links to a variety of heterocyclic acids, including tifany, furans, pyridine, p is rimidine, triazoles, imidazoles, pyrazoles, thiazole, oksazolov, isothiazole, thiadiazole, oxadiazole, triazine, pyrazine, pyridazine and isoxazoles can be found in the following books:Rodd's Chemistry of Chemistry of Carbon CompoundsVol.IVa-IVl, S.Coffey editor, Elsevier Scientific Publishing, New York,1973;ComprehensiveHeterocyclic ChemistryVol. 1-7, A.R. Katritzky and C.W. Rees editors, Pergamon Press, New York, 1984;ComprehensiveHeterocyclic ChemistryII, Vol. 1-9, A.R. Katritzky, C.W.Rees, and E.F. Scriven editors, Pergamon Press, New York,1996and serial publications, such asThe Chemistry of Heterocyclic Compounds, E.C. Taylor, editor, Wiley, New York. Heterocyclic acids, are particularly useful for preparing compounds of formula I of this invention include pyridine acid, pyrimidine acid pyrazol acid. Methods for the synthesis of typical examples of acids of each type of detail shown in the diagrams 12-35. Various heterocyclic acid and General methods for their synthesis can be found in the publication of PCT International application WO 98/57397.

Synthesis of pyrazoles of formula 4A described in scheme 12. The synthesis of compounds of formula 4A in figure 12 includes as a key stage introduction R5aDeputy alkylation or AllYouNeed of pyrazole of formula 17 compounds of formula 18 (where Lg is a leaving group, as defined above). Oxidation of the methyl group results in pyrazolylborate acid. Some of the more preferred R5bgroups include the ha shall hogenakkal.

Scheme 12

Synthesis of pyrazoles of formula 4A is also described in scheme 13. These acids can be obtained by a method in which the key stage is the metallation and carboxylation of compounds of formula 20. The group R5aenter a manner similar to the presented in figure 12, that is, by alkylation or AllYouNeed compound of formula 18. Typical examples R5bgroups include, for example, cyano, halogenated and halogen.

Scheme 13

This technique is particularly useful to obtain 1-(2-pyridinyl)pyrazolylborate acids of formula 4b (refer to preferred fragment J-6), as shown in figure 14. The interaction of the pyrazole of formula 19 with 2,3-dehalogenation formula 18a leads to good outputs 1-pildiportaal formula 20A with good specificity desired regioniii. Metallation of compounds 20A-diisopropylamide lithium (LDA) followed by quenching of the lithium salt with carbon dioxide leads to the production of 1-(2-pyridinyl)pyrazolylborate acid of formula 4b (see example 1).

Scheme 14

Synthesis of pyrazoles of formula 4C presented in figure 15. They can be obtained by the interaction of the optionally substituted phenylhydrazine of formula 21 with getoperator formula 22 to receive the receiving complex peratrovich esters of formula 23. Hydrolysis of esters results in peratrovich acids of formula 4C. This technique is particularly useful for preparing compounds in which R5arepresents optionally substituted phenyl and R5bis halogenated.

Scheme 15

Another variation of this sequence of reactions using shriley group as a protective group of carboxylic acid described in example 2.

Another method of synthesis peratrovich acids of formula 4C described in scheme 16. These acids can be obtained by the reaction of 3+2 cycloaddition of the corresponding substituted nitrilimines formula 24 or substituted propiolate formula 25 or acrylates of formula 27. For cycloaddition acrylate need additional oxidation of the intermediate pyrazoline in the pyrazole. The hydrolysis of esters of formula 28 results peratrovich acids of formula 4C. Preferred for this reaction aminoglucoside include triptoreline formulas 29 and kinodynamic formula 30. The compounds of formula 29 are known compounds (J. Heterocycl.Chem.1985, 22(2), 565-8). The compounds of formula 30 can be obtained by known methods (Tetrahedron Letters1999, 40, 2605). These techniques are particularly useful for preparing compounds in which R5a represents optionally substituted phenyl and R 5bis halogenated or bromine.

Source pyrazoles of formula 19 are known compounds or can be obtained in accordance with known methods. The pyrazole of formula 19a (compound of formula 19 where R5bis CF3and R5cis H) are commercially available. The pyrazoles of formula 19 (C) (compounds of formula 19 where R5brepresents Cl or Br and R5cis H) can be obtained in accordance with the methods described in the literature (Chem. Ber.1966, 99(10), 3350-7). A useful alternative method for obtaining compounds of 19s presented in figure 17. Metallation of sulfamoylbenzoyl formula 31 n-butyllithium with subsequent direct halogenoalkanes anion or hexachlorethane (when R5bis Cl)or 1,2-dibromotetrachloroethane (when R5bis Br) leads to the production of halogenated derivatives of formula 32. Remove sulfamoyl group triperoxonane acid (TFUC) at room temperature leads to the production of clean pyrazoles of the formula 19s with a good yield. Qualified it is clear that the compound of formula 19 (C) is tautomerism the compounds of formula 19b.

Scheme 16

Scheme 17

The synthesis of typical pyridine acids (4d) is shown in figure 18 This methodology includes the known synthesis of pyridines from complex β -ketoesters of formula 37 and 4-aminobutanol formula 36. The group of substituents R5aand R5binclude, for example, alkyl and halogenated.

Scheme 18

The typical synthesis of pyrimidine acid (4E) is shown in figure 19. This method also includes the well-known synthesis of pyrimidines from complex enamino-β-ketoesters of formula 40 and amidino formula 41. The group of substituents R5aand R5binclude, for example, alkyl and halogenated.

Scheme 19

The synthesis of typical peratrovich acids of formula 4f presented in figure 20. The interaction of complex dimethylaminoacetonitrile formula 45 with substituted hydrazine (46) leads to the production of the pyrazole of formula 47. Preferred substituents R5dinclude alkyl and halogenated, especially preferred 2,2,2-triptorelin. Esters of formula 47 is turned into acid of formula 4f standard hydrolysis methods.

Scheme 20

Synthesis peratrovich acids of formula 4g, which relate to preferred fragment J-7, where R5represents a substituted 2-peredelnyj fragment, attached in position 5 to the pyrazol ring, presented in figure 21. This synthesis is carried out in accordance with the usual technique is presented in figure 20.

Scheme 1

The synthesis of typical peratrovich acids of the formula 4h, and an alternative synthesis of compounds of formula 4f presented in figure 22.

Scheme 22

The complex interaction dimethylaminohydrolase of keeeper formula 45 with hydrazine leads to the production of the pyrazole of formula 50. The interaction of pyrazole 50 with an alkylating agent of formula 51 results in a mixture of pyrazoles of formula 52 and 53. This mixture of pyrazole isomers are easily separated using chromatography and converted into the corresponding acid 4h and 4f, respectively, Preferred substituents R5dinclude alkyl and halogenoalkane group.

Synthesis pyridinedimethanol acids of the formula 4i, which are the preferred piece of j-10, where R5represents a substituted 2-pyridinyl and is attached at position 3 of the pyrazole nucleus rings, and an alternative synthesis of compounds of formula 4g presented in figure 23. The synthesis is carried out in accordance with the General method of synthesis described in scheme 22.

Scheme 23

Total synthesis perlovich acids of the formula 4j presented in figure 24. Treatment of compounds of formula 58 2,5-dimethoxytetrahydrofuran (59) yields a pyrrole of formula 60. Formirovanie of pyrrole 60 with the floor is the group of the aldehyde of formula 61 can be carried out using standard conditions formirovaniya of Vilsmeier-khaak (Vilsmeier-Haack formylation), such as N,N-dimethylformamide (DMF) and phosphorus oxychloride. Halogenoalkane the compounds of formula 61 N-halogencontaining (NXS), such as N-chlorosuccinimide or N-bromosuccinimide, carried out preferably in position 4 of the pyrrole ring. Oxidation galogenirovannami aldehyde results in Pirogovo acid of the formula 4j. The oxidation can be carried out using a variety of standard conditions of oxidation.

Scheme 24

Synthesis of some piridincarbonova acids of the formula 4k, which relate to preferred fragment J-11, where R5represents a substituted 2-pyridinyl and is attached to the nitrogen atom of the pyrrole ring, presented in figure 25. This synthesis is carried out in accordance with the General method of synthesis described in scheme 24. The compound of formula 58A, 3-chloro-2-aminopyridine, is a known compound(seeJ.Heterocycl. Chem.1987,24(5),1313-16).

Scheme 25

Synthesis perlovich acids of the formula 4m presented in figure 26. Cycloaddition of allene of the formula 69 to vinylsulfonylacetamido formula 68 (see Pavri N.P., Trudell M.L.J. Org. Chem.1997, 62, 2649-2651) results of pyrroline formula 70. Processing of pyrroline formula 70 tetrabutylammonium fluoride (TBAF) yields a pyrrole of formula 71 Interaction of pyrrole 71 with an alkylating agent R 5d-Lg (where Lg is a leaving group, as defined above) with subsequent hydrolysis leads to Pirogovo acid of the formula 4m.

Scheme 26

Synthesis perlovich acids of the formula 4n, which relate to preferred fragment J-12, where R5is substituted phenyl or substituted 2-pyridyl and attached in position 2 of the pyrrole rings presented in figure 27. The synthesis is carried out in accordance with the General method described in scheme 26.

Scheme 27

Synthesis perlovich acids of the formula I presented in figure 28. The complex interaction α,βunsaturated esters of formula 76 p-tolylsulfochloride (TosMIC) yields a pyrrole of formula 78 (as the main link, see Z. Xu et al.,J. Org Chem.,1988, 63, 5031-5041). The interaction of the pyrrole of formula 78 with an alkylating agent R5d-Lg (where Lg is a leaving group, as defined above) with subsequent hydrolysis leads to Pirogovo acid of the formula a.

Scheme 28

Synthesis perlovich acids of the formula 4P, which are the preferred piece of J-13, where R5is substituted phenyl or substituted 2-pyridinoline ring presented in figure 29. The synthesis is carried out in accordance with the General the m method, described for scheme 28.

Scheme 29

Pyrazolylborate acid of the formula 4q, where R7is CF3can be obtained by the method presented in scheme 30.

Scheme 30

The interaction of the compounds of formula 81, where R12is1-C4alkyl, with a suitable base in a suitable organic solvent leads to the product of the cyclization of formula 82 after neutralization of the acid, such as acetic acid. A suitable base may be, for example, but without limitation only by them, sodium hydride, tert-piperonyl potassium, diminati (CH3S(O)CH2-Na+), carbonates or hydroxides of alkali metals (such as lithium, sodium or potassium), fluorides or hydroxides of tetraalkyl(such as methyl, ethyl or butyl)ammonium or 2-tert-Butylimino-2-diethylamino-1,3-dimethylpyridine-1,3,2-datafactory. Suitable organic solvent may be, for example, but without limitation only by them, acetone, acetonitrile, tetrahydrofuran, dichloromethane, dimethyl sulfoxide or N,N-dimethylformamide. The cyclization reaction is usually carried out at a temperature in the range of from about 0 to 120°C. the Influence of a solvent, a base and adding time are independent, and the choice of reaction conditions is important for information is the minimum formation of by-products. The preferred base is tetrabutylammonium fluoride.

The dehydration of compounds of formula 82 results in the compounds of formula 83 with the subsequent transformation of the functional groups of ester carboxylic acid group, carboxylic acid and obtaining the compounds of formula 4q. On dehydration affects the processing of a catalytic amount of a suitable acid. Such catalytic acid may be, for example, but without limitation, sulfuric acid. The reaction is usually carried out using an organic solvent. As it is clear to the skilled technician, the dehydration reaction can be carried out in various solvents at a temperature in the range from approximately 0 to 200°C, more preferably in the range from 0 to 100°C. For dehydration according to the method presented in figure 30, the preferred solvent comprising acetic acid, and the temperature is about 65°C. esters of carboxylic acids can be converted to carboxylic acid in a variety of ways, including nucleophilic cleavage in anhydrous conditions or hydrolytic methods using acids or bases (for an overview of these methods see T.W. Greene and P.G.M. Wuts,Protective Groups in Organic Synthesis, 2nded., John Wiley & Sons, Inc., New York, 1991, pp. 224-269). For the method presented in figure 30, the preferred hydrolytic the Kie methods with the use as a catalyst base. Suitable bases include hydroxides of alkali metals (such as lithium, sodium or potassium). For example, the ester can be dissolved in a mixture of water and alcohol, such as ethanol. After treatment with sodium hydroxide or potassium hydroxide ester its shades of obtaining sodium or potassium salt of carboxylic acid. Acidification with a strong acid, such as hydrochloric acid or sulphuric acid, yields a carboxylic acid of the formula 4q. Carboxylic acid can be isolated by methods known to the skilled specialist, including crystallization, extraction or distillation.

The compounds of formula 81 can be obtained by the method presented in scheme 31.

Scheme 31

where R7is CF3and R12is1-C4alkyl.

The process of joining the hydrazine of formula 84 ketone of formula 85 in a solvent such as water, methanol or acetic acid, yields a hydrazone of the formula 86. Qualified it is clear that for this reaction may require acid catalysis, as well as elevated temperatures depending on the molecular pattern of substitution of the hydrazone of formula 86. The interaction of the hydrazone of formula 86 with the compound of the formula 87 in a suitable organic solvent, Taco is how, for example, but without limitation only by them, dichloromethane or tetrahydrofuran, in the presence of an acid acceptor, such as triethylamine, leads to the production of the compounds of formula 81. The reaction is usually carried out at a temperature in the range from approximately 0 to 100°C. the hydrazine Compounds of formula 84 can be obtained by standard methods, such as contacting the corresponding halogen derivatives of formula 18a (scheme 14) with hydrazine.

Pyrazolylborate acid of the formula 4r, where R7represents Cl or Br, can be obtained by the method presented in figure 32.

Scheme 32

where R7represents Cl or Br and R12is1-C4alkyl.

Oxidation of compounds of formula 88 is optional in the presence of acid leads to the production of the compounds of formula 89 with the subsequent transformation of the functional groups of ester carboxylic acid functional group of a carboxylic acid and receiving, thus, the compounds of formula 4r. The oxidizing agent may be hydrogen peroxide, organic peroxides, potassium persulfate, sodium persulfate, ammonium persulfate, monopersulfate potassium (e.g., Oxone®) or potassium permanganate. For complete conversion, you must use at least one equivalent of oxidant to the equivalent of the who surveillance formula 88, preferably from about one to two equivalents. This oxidation is usually carried out in the presence of a solvent. The solvent may be a simple ether, such as tetrahydrofuran, p-dioxane and the like, a complex organic ester, such as ethyl acetate, dimethylcarbonate and the like, or a polar aprotic organic matter, such as N,N-dimethylformamide, acetonitrile and the like Acids suitable for use on stage oxidation, include inorganic acids such as sulfuric acid, phosphoric acid, etc. and organic acids such as acetic acid, benzoic acid, etc. If acid is used, it should be used in amounts of more than 0.1 equivalents relative to the compound of formula 88. For complete conversion you can use from one to five equivalents of acid. The preferred oxidizing agent is potassium persulfate, and the oxidation is preferably carried out in the presence of sulfuric acid. The reaction can be carried out by mixing the compounds of formula 88 with the desired solvent and, if used, with the acid. Then at a suitable speed may be added to the oxidizer. The reaction temperature is usually in the range from approximately 0°C to the boiling point of the solvent to obtain an acceptable response time for completion of the reaction, preferably less than hours. Target product, a compound of formula 89, may be selected by methods known to the skilled specialist, including crystallization, extraction and distillation. Methods suitable for the conversion of ester of formula 89 carboxylic acid of the formula 4r described for the circuit 30.

The compounds of formula 88 can be obtained from corresponding compounds of formula 90, as shown in scheme 33.

Scheme 33

where R7 is Cl or Br and R12is1-C4alkyl.

Treatment of compounds of formula 90 halogenation agent, usually in the presence of a solvent, leads to the corresponding halogen derivatives of formula 88. Halogenation agents that may be used include oxychloride phosphorus, trihalogen phosphorus, pentachloride phosphorus, thionyl chloride, dialoginterface, dialoginterface, oxalicacid and phosgene. Preferred are oxychloride phosphorus and pentavalent phosphorus. For complete conversion you should use at least 0.33 equivalent oxychloride phosphorus per connection formula 90, preferably from about 0.33 to 1.2 equivalent. For complete conversion you should use at least 0.20 equivalent pentachloride phosphorochloridate the compounds of formula 90, preferably from about 0.20 to 1.0 equivalent. The compounds of formula 90, where R12is1-C4alkyl, are preferred for this reaction. The usual solvents for the halogenation include halogenated alkanes such as dichloromethane, chloroform, chlorobutane and the like, aromatic solvents such as benzene, xylene, chlorobenzene and the like, ethers such as tetrahydrofuran, p-dioxane, diethyl ether and the like, and polar aprotic solvents such as acetonitrile, N,N-dimethylformamide, etc. may not Necessarily be added an organic base such as triethylamine, pyridine, N,N-dimethylaniline, etc. is also Possible to add a catalyst such as N,N-dimethylformamide. Preferred is a process in which the solvent is acetonitrile and the base is missing. Usually when using acetonitrile as a solvent requires no base or catalyst. The preferred process is carried out by mixing the compounds of formula 90 with acetonitrile. Then for a suitable time add a halogenation agent and then the mixture was kept at a certain temperature to complete the reaction. The reaction temperature is usually in the range from 20°C to the boiling point of acetonitrile, and the reaction time is usually status is made less than two hours. The reaction mass is then neutralized with inorganic base, such as sodium bicarbonate, sodium hydroxide and the like, or an organic base, such as sodium acetate. Target product, a compound of formula 88, may be selected by methods known to the skilled person skilled in the art, including crystallization, extraction and distillation.

Alternative compounds of formula 88, where R7represents Br or Cl, can be obtained by treating the corresponding compounds of formula 88, where R7is another halogen (such as Cl to obtain the compounds of formula 88, in which R7represents Br or sulphonate group such as p-toluensulfonate, hydrogen bromide or hydrogen chloride, respectively. In this way halogen or sulphonate substituent R7in the initial compound of formula 88 atom is replaced by Br or Cl hydrogen bromide or hydrogen chloride, respectively. The reaction is carried out in a suitable solvent, such as dibromomethane, dichloromethane or acetonitrile. The reaction can be conducted at atmospheric pressure or a pressure close to atmospheric, or at a pressure above atmospheric in the container under pressure. When R7in the initial compound of formula 88 is halogen, such as Cl, the reaction is preferably carried out in such clicks the zoom, the hydrogen halide formed during the reaction, is removed by spraying or other suitable means. The reaction can be conducted at a temperature in the range from approximately 0 to 100°C, the most acceptable at a temperature close to the room temperature (for example, about 10 to 40°C), more preferably in the range of from about 20 to 30°C. adding a Lewis acid as a catalyst (such as tribromide aluminum to obtain the compounds of formula 88, where R7is Br) can contribute to the reaction. The resulting compound of formula 88 distinguish conventional methods known to the skilled person skilled in the art, such as extraction, distillation and crystallization.

The parent compound of formula 88, where R7represents Cl or Br, can be obtained from corresponding compounds of formula 90, as described above. The parent compound of formula 88, where R7represents a sulphonate group, can be obtained similarly from the corresponding compounds of formula 90 standard methods such as treatment with sulphonylchloride (for example, p-toluensulfonate) and a base such as tertiary amine (e.g. triethylamine), in a suitable solvent such as dichloromethane.

Pyrazolylborate acid of the formula 4s, where R7is OCH2CF3, reformula 4t, where R7is OCHF2can be obtained by the method presented in figure 34. In this way, instead of halogenation, which is shown in scheme 33, the connection formula 90 oxidize with obtaining the compounds of formula 91. Reaction conditions such oxidation already described for the conversion of compounds of formula 88 in the compound of formula 89 presented in figure 32.

Then the compound of formula 91 alkylate with the formation of the compounds of formula 93 (R7is OCH2CF3) by contact with an alkylating agent CF3CH2Lg (92) in the presence of a base. In the alkylating agent of the formula 92 Lg represents a group to be deleted in the course of nucleophilic reactions, such as halogen (such as Br, I), OS(O)2CH3(methanesulfonate), OS(O)2CF3, OS(O)2Ph-p-CH3(p-toluensulfonate) and the like; it is convenient to use methanesulfonate. The reaction is carried out in the presence of at least one equivalent of base. Suitable bases include inorganic bases such as carbonates and hydroxides of alkali metals (such as lithium, sodium or potassium), and organic bases such as triethylamine, diisopropylethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene. The reaction is usually conducted in a solvent, which may include alcohols such as methanol and ethanol, halogenated alkanes, such as dichlo is methane, aromatic solvents such as benzene, toluene and chlorobenzene, ethers, such as tetrahydrofuran, and polar aprotic solvents such as acetonitrile, N,N-dimethylformamide and the like, Alcohols and polar aprotic solvents are preferred for use with inorganic bases. The preferred potassium carbonate as base and acetonitrile as solvent. The reaction is usually carried out at a temperature in the range from approximately 0 to 150°C, the most typical is the temperature interval from room temperature to 100°C.

Scheme 34

where R12represents C1-C4alkyl and Lg represents a leaving group.

The compound of formula 91 can also be alkilirovanii with the formation of the compounds of formula 95 (R7is OCHF2) contacts with diperkirakan obtained from CHClF2in the presence of a base. The reaction is usually conducted in a solvent, which may include ethers, such as tetrahydrofuran or dioxane, and polar aprotic solvents such as acetonitrile, N,N-dimethylformamide, etc. may be selected from inorganic bases such as potassium carbonate, sodium hydroxide or sodium hydride. Preferably the reaction is carried out using potassium carbonate or N,N-dimethyl what armagedom as solvent. Esters of formula 93 or 95 can be selected by traditional methods, such as extraction. Esters can then be converted into a carboxylic acid of formula 4 or 4t ways already described for the conversion of compounds of formula 83 in the compounds of formula 4q in scheme 30.

As shown in scheme 35, the compounds of formula 90 can be obtained from compounds of formula 84 (see diagram 31).

Scheme 35

where R12represents C1-C4alkyl.

In this way the connection of the hydrazine of formula 84 is subjected to contacting with the compound of the formula 96 (may be difficult or fumaric maleate esters or a mixture thereof) in the presence of base and solvent. The base is usually alkoxide metal salt, such as sodium methoxide, potassium methoxide, ethoxide sodium, atoxic potassium tert-piperonyl potassium tert-piperonyl lithium, etc. you Should use more than 0.5 equivalent basis based on the compound of formula 84, preferably from 0.9 to 1.3 equivalents. You should use more than 1.0 equivalent of compound of formula 96, preferably from 1.0 to 1.3 equivalent. Can be used proton polar and polar aprotic organic solvents, such as alcohols, acetonitrile, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide is so Preferred solvents are alcohols, such as methanol and ethanol. Particularly preferably, the alcohol was the same that was used to obtain fumaric or malatova of ester and alkoxides Foundation. The reaction is usually carried out by mixing the compounds of formula 84 and base in a solvent. The mixture can be heated or cooled to the desired temperature and the compound of formula 96 can be added within a certain period of time. Usually the reaction temperature is in the range from 0°C to the boiling point of the solvent. To increase the boiling point of the solvent, the reaction can be conducted at a pressure higher than atmospheric pressure. Usually the preferred temperature in the range of from about 30 to 90°C. the Time of addition can be as small as possible heat transfer. Typically, the time added is from 1 minute to 2 hours. The optimum reaction temperature and time add change depending on the identity properties of the compounds of formula 84 and the compounds of formula 96. After the addition the reaction mixture was kept for a certain period of time at the reaction temperature. Depending on the reaction temperature for the necessary time, during which the mixture was kept at the reaction temperature may be from 0 to 2 hours is. Usually this time is from 10 to 60 minutes. The reaction mass is then acidified by the addition of organic acids such as acetic acid, etc. or an inorganic acid such as hydrochloric acid, sulfuric acid, etc. depending on the reaction conditions and methods of selection of product functional group-CO2R12the compounds of formula 90 may be hydrolyzed to CO2N; for example, the presence of water in the reaction mixture can promote hydrolysis. If there is a carboxylic acid group (-CO2N), it can again turn in a group-CO2R12where R12is1-C4alkyl, methods of esterification are well known in this field. Target product, a compound of formula 90 can be isolated by methods known to the skilled technician, such as crystallization, extraction or distillation.

It is known that some reagents and reaction conditions described above for preparing compounds of formula I may be incompatible with certain functional groups present in the intermediate products. In such cases, to obtain the target products will be used to protect/unprotect or vzaimoprevrascheny functional groups in the synthesis. The application and the choice of protective groups will be apparent to kV is limitirovannoe specialist in the field of organic synthesis (see, for example, Greene, T.W.; Wuts, P.G.M.Protective Groups in Organic Synthesis, 2nded.; Wiley: New York,1991). Qualified it is clear that in some cases, after the introduction of the reagent contained in any individual scheme, it may be required the implementation of additional stages of synthesis, not described in detail in the diagram to complete the synthesis of compounds of formula I. a Qualified specialist is also clear that may require the implementation of a combination of stages presented in the above schemes in an order other than indicated on the diagram, to obtain compounds of formula I.

It is assumed that a qualified expert in this field can obtain the compounds of formula I of this invention, using the above description in its entirety. Thus, the following examples should be considered only as illustrative and in no way limit the present invention. The percentages indicated in the examples are by mass percent, except mixtures of solvents for chromatography or except when other provision is negotiated separately. Parts and percentages for mixtures of chromatographic solvents are given in volume, unless otherwise specified condition.1H-NMR spectra are given in ppm in the lower region from tetrameters the Lana; with means singlet, d means doublet, t means triplet, square means Quartet, m means multiplet, DD means double doublet, dt means a double triplet, USS means broadened singlet.

EXAMPLE 1

Obtaining N-[2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine

Stage a: 3-chloro-2-[3-(trifluoromethyl)-1H-pyrazole-1-yl]pyridine

To a mixture of 2,3-dichloropyridine (99,0 g, 0.67 mol) and 3-cryptomaterial (83 g, 0.61 mol) in dry N,N-dimethylformamide (300 ml) is added potassium carbonate (166,0 g, 1.2 mol) and then the reaction mixture is heated at 110-125°C for 48 hours. The reaction mixture is cooled to 100°C and filtered through diatomaceous accelerator filtering Celit® to remove solids. N,N-Dimethylformamide and excess dichloropyridine removed by distillation at atmospheric pressure. Distillation of the product under reduced pressure (BP. 139-141°C/7 mm Hg) leads to obtain the desired intermediate product in the form of a clear yellow oil (to 113.4 g).

1H-NMR (CDCl3): δ is 6.78 (s, 1H), was 7.36 (t, 1H), to 7.93 (d, 1H), 8,15 (s, 1H), 8,45 (d, 1H).

Stage:obtain 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

To a solution of the pyrazole nucleus of the product obtained at stage A (105,0 g, 425 mmol)in dry tetrahydrofuran (700 ml) at -75°C across which the cannulae add solution diisopropylamide lithium (425 mmol) in dry tetrahydrofuran (300 ml), cooled to -30°C. the resulting deep red solution is stirred for 15 minutes, after which through the solution at -63°C bubbled with carbon dioxide until then, until the solution becomes pale yellow and does not stop the heat. The reaction solution is again stirred for 20 minutes and then the reaction quenched with water (20 ml). The solvent is removed under reduced pressure, the reaction mixture was partitioned between simple ether and 0.5 N. aqueous sodium hydroxide solution. Aqueous extracts washed with simple ether (3x), filtered through diatomaceous accelerator Celite filtration® to remove residual solids, and then acidified to a pH of approximately 4, which yields an orange oil. Water the mixture is vigorously stirred and add a further quantity of acid to reduce the pH to 2.5-3. Orange oil is transformed into a granular solid, which was filtered, washed successively with water and 1 N. hydrochloric acid and dried in vacuum at 50°C, getting listed in title product in the form of not-quite-white solid (130 g). (The product of the other boot received in accordance with the same methods, melts at 175-176°C).

1H-NMR (DMSO-d6): δ to 7.61 (s, 1H), 7,76 (DD, 1H), 8,31 (d, 1H), at 8.60 (d, 1H).

Stage: getting 8-methyl-2H-3,1-b is isoxazine-2,4-(1H)-dione

To a solution of 2-amino-3-methylbenzoic acid (6 g) in dry 1,4-dioxane (50 ml) added dropwise a solution of trichloromethylcarbonate (8 ml) in dry 1,4-dioxane (25 ml), cooling the reaction mass in an ice bath to maintain the reaction temperature below 25°C. during the addition a white precipitate is formed. The reaction mixture was stirred at room temperature overnight. Settled solids are removed by filtration, washed with 1,4-dioxane (2x20 ml) and hexane (h ml) and dried in the air, getting 6,51 g not quite white solid.

1H-NMR (DMSO-d6): δ of 2.33 (s, 3H), 7,18 (t, 1H), to 7.59 (d, 1H), 7,78 (d, 1H), 11,0 (USS, 1H).

Stage D: obtain 1-(3-chloro-2-pyridinyl)-N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To a solution of carboxylic acid, obtained in stage B (28 g, 96 mmol), in dichloromethane (240 ml) is added N,N-dimethylformamide (12 drops) and oxacillin (15,8 g, 124 mmol). The reaction mixture was stirred at room temperature until, until you cease to be allocated gas (approximately 1.5 hours). The reaction mixture was concentrated in vacuo to obtain the crude acid chloride in the form of oil, which is used without further purification. The crude acid chloride was dissolved in acetonitrile (95 ml) and added to a solution of benzoxazin-2,4-dione, poluchennogo is as described on the stage, in acetonitrile (95 ml). The resulting mixture was stirred at room temperature (approximately 3 minutes). To the mixture is added pyridine (95 ml), the resulting mixture is heated at about 90°C (approximately 1 hour). The reaction mixture is cooled to about 35°C and added Isopropylamine (25 ml). The reaction mixture exothermically heated in the process of adding and then maintained at a temperature of about 50°C (approximately 1 hour). Then the reaction mixture was poured into ice-cold water and stirred. The formed precipitate is filtered off, washed with water and dried in vacuum over night, getting 37,5 g specified in the title compound as a tan solid.

1H-NMR (CDCl3): δ of 1.23 (d, 6H), of 2.21 (s, 3H), 4,2 (m, 1H)and 5.9 (d, 1H), 7,2 (t, 1H), and 7.3 (m, 2H), 7,31 (s, 1H), and 7.4 (m, 1H), and 7.8 (d, 1H), and 8.5 (d, 1H), 10,4 (s, 1H).

Stage E: obtaining N-[2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine

Stir a solution of the compound obtained in stage D (1.2 g, 2.6 mmol)in 8 ml of phosphorus oxychloride is refluxed for 8 hours. Warm the reaction solution was poured on taken in a large excess of ice and then immediately add 100 ml of ethyl acetate (after all the ice melts). The solution is stirred and enable the remaining ice to melt, telecity layer is separated, washed with water, aqueous saturated sodium bicarbonate solution and saturated salt solution. After drying over magnesium sulfate the solvent is removed in vacuum, obtaining the crude oily residue solid yellow substance. Purification with flash chromatography on silica gel (4:1, hexane/ethyl acetate as eluent) results 450 mg specified in the title compounds, the compounds of this invention allocated in the form of a white solid (TPL 175-176°C).

1H-NMR (CDCl3): δ of 1.23 (d, 6H), of 1.75 (s, 3H), 4,07 (m, 1H), 7,15-7,28 (m, 3H), 7,45 (m, 1H), of 7.90 (d, 1H), 7,95 (d, 1H), 8,55 (d, 1H).

EXAMPLE 2

Obtaining N-[2-[1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene-2-propanamine

Stage A: obtain 1-(2-chlorophenyl)-5-(2-furanyl)-3-(trifluoromethyl)-1H-pyrazole

To a solution of 1-(2-furin)-4,4,4-triptorelin-1,3-dione (105 g, 0.51 mol) in glacial acetic acid (220 ml) is added sodium acetate (42 g, 0.51 mol). The temperature increases to about 34°C. To the resulting solution was dropwise within 10 minutes add the hydrochloride of 2-chlorophenylhydrazone (90 g, 0.5 mol) to obtain a creamy suspension. The mixture is heated to about 60°C for approximately 45 minutes. Acetic acid is removed on a rotary evaporator with a bath temperature of 65°C. the Obtained oily residue is added to approximately 800 ml of water is under vigorous stirring, receiving a heterogeneous mixture. After 15 minutes, to the mixture dichloromethane (500 ml) and the mixture is divided into phases. The aqueous phase is extracted with 300 ml dichloromethane. The combined organic phases are washed with water and saturated sodium bicarbonate solution, then dried with MgSO4and filtered. Volatile components are removed at the rotary evaporator. The crude product consists of 151 g of a dark red oil, which contains approximately 89% of the target product and 11% of regioisomeric pyrazole (determined by NMR analysis).

Stage: obtain 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

Selected crude product stage (approximately 89%, 56,0 g, 0.18 mol) is dissolved in acetonitrile (400 ml) and add a solution of NaH2PO4(120 g, 0.87 mol) in 520 ml of water. To the mixture dropwise over 10-15 minutes, add a solution of sodium hypochlorite (5.25% in water, 128 g, 2.6 mol). The resulting orange solution was kept at room temperature for 30 minutes. The reaction mixture was cooled in an ice bath and added dropwise a solution of NaClO2in 560 ml of water, keeping the temperature below 11°C. When this occurs, gases, and to absorb the released chlorine use scrubber with an aqueous sodium hydroxide. After complete addition, the reaction mixture was kept cooled in an hour is a, then allow it to warm to room temperature over night. To the reaction mixture are added dropwise 80 ml of concentrated hydrochloric acid to achieve a pH below 3. The reaction mixture is extracted twice with ethyl acetate and the combined organic extracts dropwise with stirring to a cooled (<15° (C) a solution of 300 grams of NaHSO3in 1300 ml of water. The mixture is divided into phases and the aqueous phase extracted with ethyl acetate. The combined organic phases are washed with a saturated solution of salt, dried (MgSO4), filtered and concentrated in vacuo. The residue is transferred to chlorobutane and again concentrated (twice). The obtained solid brown triturated in 100 ml of ethyl ether in hexane (1%). Add small portions chlorobutane, promoting granulation solids. The product is filtered, washed with hexane and dried. The product consists of 40.8 g of tan solid, which is essentially pure, as shown by the data1H-NMR.

Stage C: obtain 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbonylchloride

Selected crude 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (40,8 g, 0.14 mol) is dissolved in methylene chloride (300 ml). The solution is treated with oxalylamino (15.7 ml, 0.18 mol), then N,N-Dimethylol what amidon (12 drops). Soon after adding N,N-dimethylformamide catalyst is observed gas evolution. The reaction mixture is stirred for about 20 minutes at room temperature, then refluxed for 35 minutes. Volatile components are removed by concentration of the reaction mixture on a rotary evaporator with a bath temperature of 55°C. the Crude product, approximately 43 g of light yellow oil, used in the next stage without additional purification.

Stage D: obtain 1-(2-chlorophenyl)-N-[2-methyl-6-[[(1-methylethyl)amino]carbonyl]phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide

To the selected specified in the header of example 1 stage connection (22,3 g, 0,126 mol)is suspended in acetonitrile (100 ml), add the crude 1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbonylchloride (43 g). The mixture is diluted with 350 ml of pyridine and heated at about 95°C for 2 hours. The mixture is cooled to 29°C, then treated with Isopropylamine (32,2 ml, 0.38 mol). Reaction mass is spontaneously heated to 60°C, and maintained at a temperature of about 50°C for one hour, then stirred overnight. The reaction mixture is poured into 1 l of water and stirred. The obtained solid is filtered off and washed with water. Wet the filter cake is transferred into a mixture of dihormati the a and methanol, the water is discarded and the organic phase is dried with molecular sieves and filtered. Volatile components are removed at the rotary evaporator. The crude product is triturated with a mixture of ether/hexane (1:1), filtered and washed with hexane getting 42.6 g of a light brown solid (TPL 230-231°C).

1H-NMR (DMSO-d6): δ or 10.3 (s, 1H), and 7.1-7.5 (m, 8H)and 5.9 (d, 1H), 4,2 (m, 1H), of 2.21 (s, 3H), of 1.21 (d, 6H).

Stage E: obtaining N-[2-[1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine

To headline the connection stage D (1.2 g, 2.7 mmol)dissolved in 8 ml of dichloromethane, add 5 ml of thionyl chloride and the solution is refluxed for 8 hours. The solvent is removed in vacuo and the residue partitioned between 70 ml of ethyl acetate and water. The organic layer was separated, washed with water, saturated sodium bicarbonate solution and saturated salt solution. The organic phase is dried over magnesium sulfate and the solvent is removed in vacuum, obtaining the crude oily residue solids. Purification with flash chromatography on silica gel (elution: hexane/ethyl acetate, 2:1) and filtration of the hexane yield 700 mg specified in the title compounds, the compounds of this invention allocated in the form of a white solid (TPL 133-135°C).

1N-I Is R (300 MHz, CDCl3): δ of 7.90 (d, 1H), EUR 7.57-the 7.43 (m, 4H), 7,30-7,13 (m, 3H), 4,0 (m, 1H), 1,80 (s, 3H), of 1.21 (d, 6H).

EXAMPLE 3

Getting 7,9-dichloro-5-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-2,3-dihydroimidazo[1,2-c]hintline

Stage A: obtain 2,4-dichloro-6-(4,5-dihydro-1H-imidazol-2-yl)benzoylamino

To a solution of Ethylenediamine (1.2 ml, 18 mmol) in ethyl ether (50 ml) at -20°C add n-utility (6.4 ml, 2.5 M in hexano, 16 mmol). The mixture was stirred at 0°C for 0.3 hour, then add 2,4-dichloro-6-triptorelin (0,92 g,4.2 mmol). The mixture was stirred at 0°C for an additional 1.5 hours, then add water (0,36 ml, 20 mmol) and the solvent is removed under reduced pressure. Purification column flash chromatography (silica gel, 1%-10% methanol in dichloromethane) gives specified in the header of the stage And the compound (0.35 g) as a solid yellow color.

1H-NMR (CDCl3): δ 7,30 (d, 1H), 7.23 percent (d, 1H), 6,8 (USS, 2H), 4,7-4,6 (USS, 1H), of 3.77 (USS, 4H).

Stage: getting 7,9-dichloro-5-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-2,3-dihydroimidazo[1,2-c]hintline

To a solution of 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (0.6 g, 2.02 mol) (see example 1, step B) in dichloromethane (10 ml)containing dimethylformamide (1 drop), add oxalicacid (198 μl, 2.22 mmol). The mixture is stirred at room temperature is round for two hours, concentrate under reduced pressure and re-dissolved in dichloromethane (5 ml). Seven-tenths of this solution added to the solution specified in the header of the stage And the compound (0.3 g, 1.3 mmol), triethylamine (272 ml of 1.95 mmol) and dimethylaminopyridine (16 mg, 0.13 mmol) in dichloromethane (5 ml) and the resulting mixture was stirred at room temperature overnight. Add a saturated solution of sodium bicarbonate and the mixture is then filtered through a column of Celite®. Concentration of the filtrate yields a substance that cleans column flash chromatography (silica gel, elution: 1%, 2%, 5% methanol in dichloromethane, then 10%, 20% acetone in chloroform, then 5% methanol in dichloromethane). The selection of the first aliremove substance gives specified in the header of the example 3, the connection, the connection of the present invention, in the form of a yellow solid substance (62 mg). Second allerfree the substance is 1-(3-chloro-2-pyridinyl)-N-[2,4-dichloro-6-(4,5-dihydro-1H-imidazol-2-yl)phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide, the intermediate of example 3.

1H-NMR (CDCl3): δ 8,5 an 8.4 (d, 1H), 7,9 (d, 1H), 7,46 (d, 1H), 7,41 (d, 1H), and 7.4 (DD, 1H), 7,31 (s, 1H), of 3.77 (s, 4H).

According to the methods described above and known in the field of methods, get connections, are presented in tables 1-21. In these tables use the following abbrev atory: t means tertiary, s means secondary, n means normal, i means ISO, Me means methyl, Et means ethyl, Pr means propyl, i-Pr means isopropyl, Bu means butyl.

Table 1

Table 2

Table 3

Table 4

Table 5

Table 6

Table 7

Table 8

Table 9

Table 10

Table 11

Table 12

Table 13

Table 14

Table 15

Table 16

Table 17

Table 18

Table 19

Table 20

Table 21

Obtaining drugs/applicability

The compounds used in accordance with this invention are usually applied in the form of a preparation or composition with agricultural acceptable carrier comprising at least one liquid diluent, a solid diluent or a surfactant. The ingredients of the product or composition is chosen in accordance with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature. Useful drugs include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions), etc. that may not necessarily thicken in the gels. Useful drugs include solids, such as dusty, powders, granules, pellets, tablets, films, etc. that may be water-dispersible ("wettable") or water-soluble. The active ingredient can be introduced in (micro)capsule and additionally introduced into the suspension or solid drug; alternative all of the medicine the active ingredient can be encapsulated or coated). Encapsulation can adjust or delay the release of the active ingredient. Drugs that can be applied by spraying or spray the Institute of economy and management, you can distribute in a suitable medium and use in volumetric doses from about one to several hundred liters per hectare. Highly concentrated compositions are used primarily as intermediates for subsequent preparation of the drug.

Preparations usually contain an effective amount of the active ingredient, diluent and surfactant in the following approximate intervals, which adds up to 100 wt.%.

wt.%
The active ingredientThinnerSAC
Water-dispersible and water-soluble granules, tablets and powders5-900-941-15
Suspensions, emulsions, solutions (including emulsion concentrates)5-5040-950-15
Dusty1-2570-990-5
Granules and pellets0,01-995-99,990-15
Highly concentrated component is icii 90-990-100-2

Normal solid diluents are described in Watkins publishing, et al.,Handbook of Insecticide Dust Diluents and Carriers, 2ndEd., Dorland Books, Calwell, New Jersey. Conventional liquid diluents are described in the publication Marsden,Solvents Guide, 2ndEd., Interscience, New York, 1950,McCutcheon's Detergenys and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey; Sisely and Wood,Encyclopedia of Surface Active Agents, Chemical Publ, Co., Inc. New York, 1964, and also provides a list surfactants and recommended use. All drugs may contain minor amounts of additives to reduce foam, caking, corrosion, microbial growth, etc. or thickeners for increasing the viscosity.

Surfactants include, for example, polyethoxysiloxane alcohols, polyethoxysiloxane ALKYLPHENOLS, polyethoxysiloxane sorbitane esters of fatty acids, diallylmalonate, alkyl sulphates, alkylbenzenesulfonate, organosilicone, N,N-dialkylamide, ligninsulfonate, condensation products of naphthalenesulfonate with formaldehyde, polycarboxylate and block copolymers of polyoxyethylene/polyoxypropylene. Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silicon dioxide, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and biker eat sodium and sodium sulfate. Liquid diluents include, for example, water, N,N-dimethylformamide, dimethylsulfoxide, N-alkylpyridine, ethylene glycol, propylene glycol, paraffins, alkyl benzenes, alkylnaphthalene, olive oil, castor oil, linseed oil, Tung oil, sesame oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil and coconut oil, esters of fatty acids, ketones, such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, and alcohols, such as methanol, cyclohexanol, and decanol tetrahydrofurfuryl alcohol.

Solutions, including emulsion concentrates can be obtained by simple mixing of the ingredients. Dusty and powders can be obtained by blending and usually by grinding, for example, a hammer mill or a jet mill. Suspension usually get wet mixing (see, for example, U.S. Patent No. 3060084). Granules and pellets can be obtained by the application of active substances by spraying on pre-obtained granular media or methods of agglomeration (see Browing, "Agglomeration",Chemical Engineering, December 4, 1967, pp.147-48,Perry's Chemical Engineer''s Handbook, 4thEd., McGraw-Hill, New York, 1963, pages 8-57 and following; international PCT application WO 91/13546. Pellets can be obtained in accordance with the methods described in U.S. Patent No. 4172714. Water-dispersible and water-soluble granules can be obtained is accordance with the methods described in U.S. Patent No. 4144050 and 3920422 and Application Germany 3246493. Tablets can be obtained in accordance with the methods described in U.S. Patent No. 5180587, U.S. Patent No. 5232701 and U.S. Patent No. 5208030. Film can be obtained in accordance with the methods described in the Application great Britain No. 2095558 and in U.S. Patent No. 3299566.

Additional information pertaining to methods of producing drugs, see T.S. Woods, "The Formulator''s Toolbox - Product Forms for Modern Agriculture" inPesticide Chemistry and Bioscience,The Food-Environment Challenge, T. Brooks and T.R. Roberts, Eds., Proceedings of the 9thInternational Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. Cm. also U.S. patent No. 3235361 (column 6 line 16-column 7, line 19 and examples 10-41); No. 3309192 (column 5, line 43 column 7 pages 62 and examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182); No. 2891855 (column 3 line 66 to column 5, line 17 and examples 1-4), and Klingman,Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp.81-96; Hance et al.,Weed Control Handbook, 8thEd., Blackwell Scientific Publications, Oxford, 1989.

The following examples all percentages are percentages based on the mass, and all products obtained by traditional methods. Rooms compounds refer to compounds in table A.

An example of a

Wettable powder

connection 465,0%
dodecylpropane angelically ether 2,0%
ligninsulfonate sodium4,0%
silicoaluminate sodium6,0%
montmorillonite (calcinated)23,0%

The example In

Granules

connection 410,0%
granules attapulgite (low-volatile substance, of 0.71/0.30 mm; sieve No. 25-50 (US standard))90,0%

Example With

Extruded pellets

connection 425,0%
anhydrous sodium sulfate10,0%
untreated ligninsulfonate calcium5,0%
alkylnaphthalene sodium1,0%
calcium/magnesium bentonite59,0%

Example D

Emulsion concentrate

connection 420,0%
the mixture of oil-soluble sulfonates and simple polyoxyethylenated esters10,0%
Isophorone70,0%

Example E

Granules

soedinenie 0,5%
Cellulose2,5%
Lactose4,0%
corn flour93,0%

The compounds used in accordance with this invention, are characterized by favorable metabolic properties and/or character of soil residues and active, which can be used to combat agricultural and non-agricultural invertebrate pests in a wide range. (In the context of this invention the term "combating invertebrate pests" means the suppression of the development of invertebrate pests (including mortality), which causes a significant reduction in consumed their food or other damage or damage caused by the pest, and related expressions are defined similarly).

The term "invertebrate pest", which was used in the description above, includes arthropods, gastropods and nematodes, representing pests, the damage from life which may have economic value.

The term "arthropods" includes insects, mites, spiders, Scorpions, centipedes, of, woodlice and symphylans. The term "gastropod" includes snails, slugs and other representatives of the Stylommatophora. The term "nematode" is before all helminths, such as roundworms, heartworms and herbivorous nematodes (Nematoda), flukes (Trematoda), Acanthocephala, and tapeworms (Cestoda). A qualified specialist in this field it is clear that not all compounds are equally effective against all pests. The compounds used in accordance with this invention exhibit activity against economically important agricultural and non-agricultural pest. The term "agriculture" refers to the production of field crops such as food crops, and fiber crops, and includes the cultivation of cereal crops (e.g. wheat, oats, barley, rye, rice, maize), soybeans, vegetable crops (e.g. lettuce, cabbage, tomatoes, beans), potatoes, sweet potatoes, grapes, cotton and fruits, ripe on the trees (for example, pome fruits, stone fruits and citrus fruit crops). The term "non-agricultural" refers to other orchard crops (e.g., forest, greenhouse plants, plants grown in nurseries, or ornamental plants that do not grow in the field) and use on these crops and their pests, public health and animal health, home and commercial structures in the household and the products are stored, as well as to pests encountered in these the areas. Given the wide range of invertebrate pests and economic importance of protecting them from damage or damage to invertebrate pests) agricultural crops of cotton, corn, soybean, rice, vegetables, potatoes, sweet potatoes, grapes and fruit grown on trees, apply for combating invertebrate pests represent a preferred embodiment of the present invention. Agricultural and non-agricultural pests include insect larvae of Lepidoptera, such as Hiking worms, worms, Geometridae, and heliothines in the family Noctuidae (e.g., fall armyworm (Spodoptera fugiperda J.E. Smith), beet marching worms (Spodoptera exiguaHübner), scoop Upsilon (Agrotis ipsilonHufnagel), scoop or (Trichoplusia niHübner), scoopHeliothis virescens Fabricius); drillers, czechanski, caterpillars, coneworms, mermaidy and pests, skeletonema leaves the family Pyralidae (e.g., corn borer (Ostrinia nubilalisHübner), caterpillar pests of citrus (Amyelois transitellaWalker), Ognevka (Crambus caligmosellusClemens), meadow moths (Herpetogramma licarsisalisWalker)); leafrollers, leafrollers pockety, moth and caterpillar pests of fruit of the family Tortricidae (e.g., Codling moth (Cydia pomonellaLinnaeus), grape moth (Endopiza viteanaClemens), tortrix Oriental peach (Grpholita molesta Busck)); and many other economically important Lepidoptera (e.g., the cabbage moth (Plutella xylostellaLinnaeus), pink boxed worm (Pectinophora gossypiellaSaunders), Gypsy moth (Lymantria disparLinnaeus)); larvae and adults of troop Blattodea including cockroaches families Blattellidae and Blattidae (e.g., cockroach black (Blatta orientalisLinnaeus), Asian cockroach (Blatella asahinaiMizukubo), cockroach red (Blattella germanicaLinnaeus), brownbanded cockroach (Supella longipalpaFabricius), American cockroach (Periplaneta americanaLinnaeus), brown cockroach (Periplaneta brunneaBurmeister), Madeira cockroach (Leucophaea maderae Fahricius)); larvae feeding on foliage, and adults of the order of Coleoptera including weevils families Anthribidae, Bruchidae, and Curculionidae (e.g., the weevil cotton (Anthonomus grandisBoheman), rice weevil water (Lissorhoptrus oryzophilusKuschel), granary weevil (Sitophilus granariusLinnaeus), rice weevil (Sitophilus oryzaeLinnaeus)); excavation of a flea, beetle blaska potato flea beetle root, leaf beetles, Colorado potato beetles, and moths-minelayers number of the family Chrysomelidae (e.g., Colorado potato beetle (Leptinotarsa decemlineataSay), leaf corneil corn (Diabronica virgifera virgiferaLeConte)); Khrushchev and other flea beetle family Scaribaeidae (for example, garden chafer Japanese (Popillia japonicaNewman and garden chafer European (Rhizotrogus majalisRazoumowsky)); koreeda family Dermestidae; wireworms family Elateridae; bark beetles of the family Scolytidae and much is s the larval large family Tenebrionidae. In addition to agricultural and non-agricultural pests include adult and larvae squad Dermaptera, including earwig family Forficulidae (e.g., haverty common (Forflcula auriculariaLinnaeus), haverty black earwig) (Chelisoches morioFabricius)); adults and larvae units Hemiptera and Homoptera such as bugs-kanaky family Miridae, cicadas family Cicadidae, cycatki (for example,Empoascaspp.) the family Cicadellidae, delphacidae families Fulgoroidae and Delphacidae, the humpback family Membracidae, listblock family Psyllidae, whiteflies family Aleyrodidae, aphids of the family Aphididae, phylloxera family Phylloxeridae, mealybugs of the family Pseudococcidae, scales of the family Coccidae, Diaspididae and Margarodidae, bugs-lace-family Tingidae, bugs-defenders of the family Pentatomidae, white-winged bugs (e.g., Blissus spp.) and other bugs of the family Lygaeidae, pszenicy family Cercopidae, squash bugs of the family Coreidae, and red bugs and krasnolipe family Pyrrhocoridae. In addition, pests also include adult and larvae squad Acari (mites)such as spider mites and red mites in the family Tetranychidae (e.g., clasic spider (Panonychus ulmiKoh), clasic spider bimaculated (Tetranychus urticaeKoh), clasic McDaniel (McDaniel) (Tetranychus mcdanieliMcGregor)), flat mites in the family Tenuipalpidae (e.g., clasic flat citrus (citrus flat mite) (Brevipalpus lewisiMcGregor)), rust and haloorange CL is the soup of the family Eriophyidae and other mites, eating the foliage, and mites, which are important for human health and givotnih, i.e. ticks contained in the dust (dust mites) family Epidermoptidae, zeleznici family Demodicidae, grain mites (grain mites) family Glycyphagidae, ticks squad Ixodidae (e.g., deer tick (deer tick) (Ixodes scapularisSay), mite Australian (Australian paralysis tick) (Ixodes holocyclusNeumann), Ixodes tick variable (Dermacentor variabilisSay), mite one-star (lone star tick) (Amblyomma americanumLinnaeus) and cestocide (scab and itch mites) mites in the families Psoroptidae, Pyemotidae, and Sarcoptidae; adult and immature specimens of Orthoptera order, including locusts (grasshoppers), these grasshoppers (locusts) and crickets (e.g., locusts (such asMelanoplus sanguinipesFabricius,M. differentialisThomas), American locust (for example,Schistocerca americanaDrury), desert locust (SchistocercagregariaForskal), migratory locust (Locusta migratoriaLinnaeus), house cricket (Acheta domesticusLinnaeus), mole crickets (Gryllotalpaspp.)); adults and immature individuals detachment Diptera, including moth-minelayers number, Midge, petrotrace (Tephritidae), Swedish fly (for example,Oscinella fritLinnaeus), soil maggots, flies room (for example,Musca domesticaLinnaeus), lesser house flies (e.g.,Fannia canicularisLinnaeus,F.femoralisStein), jagalchi autumn (for example,Stomoxys calcitransLinnaeus), face flies, gigalo small cow, blow flies (e.g.,Chrysomya spp., Phormia spp.), and other mehoopany flying pests, gigalo horse is I (for example, Tabanusspp.), bot flies (e.g.,Gastrophilusspp.,Oestrusspp.), larvae bullish gadfly (for example,Hypodermaspp.), the deer flies (e.g.,Chrysopsspp.), Runci sheep (for example,Melophagus ovinusLinnaeus) and other members of the squad Brachycera, mosquitoes (e.g.,Aedesspp.,Anophelesspp.,Culexspp.), black flies (e.g.,Prosunuliumspp.,Simuliunspp.), biting midges, black flies, sciarids, and other representatives of the order Nematocera; adults and immature individuals detachment Thysanoptera, including thrips (Thrips tabaciLindeman) and other poseleniya feeding on foliage; insect pests of the order Hymenoptera including ants (for example, Murowa-tree-borer (Camponotus ferrugineusFabricius), the ant-tree-borer, Pennsylvania (Camponotus pennsylvanicusDeGeer), Pharaoh ant (Monomorium pharaonisLinnaeus), Tasmania (Wasmannia auropunctataRoger), ant Richter (Solenopsis geminataFabricius), red imported fire ant (Solenopsis invictaBuren), Argentine ant (Iridomyrmex humilisMayr), paratrechina (Paratrechina longicornisLatreille), ant sod (Tetramorium caespitumLinnaeus), cornfield ant (Lasius alienusForster), the ant Tapinoma sessile (Tapinoma sessileSay)), bees (including bees-the carpenters), hornets, yellow jackets and ocb; insect pests of the detachment Isoptera, including termite yellow-footed (Reticulitermes flavipesKollar), termiteReticulitermes hesperus(Reticulitermes hesperusBanksu), termiteCoptotermes formosanus(Coptotermes formosanusShiraki), West Indian Drywood termit (IncisitermesimmigransSnydexand other termites important economy is eskay perspective; insect pests of detachment Thysanura such as Chechulina (LepismasaccharinaLinnaeus) and Chechulina home (Thermobia domesticaPackard); insect pests of the detachment Mallophaga, including the head louse (Pediculus humanus capitisDe Geer), body louse (body louse) (Pediculus humanus humanusLinnaeus), pakhoed (Menacanthus stramineusNitszch), flashed dog (Trichodectes canis De Geer), pogoed chicken petrobrazi (Goniocotes gallinaeDe Geer), sheep louse (Bovicola ovisSchrank), Short-nosed cattle louse (Haematopinus eurysternusNitzsch), long-nosed cattle louse (LinognathusvituliLinnaeus) and other sucking and biting lice are parasites that are parasitic on man and animals; insect pests of the detachment Siphonoptera including the rat flea (oriental rat flea) (Xenopsylla cheopisRothschild), cat flea (CtenocephalidesfelisBouche), dog flea (Ctenocephalldes canisCurtis), flea chicken (hen flea) (Ceratophyllus gallinaeSchrank), flea suction (Echidnophaga gallinaceaWestwood), human flea (Pulex irritansLinnaeus) and other fleas infecting mammals and birds. Additional arthropods pests with coverage, include spider squad Araneae, such as the brown recluse spider (Loxosceles reclusaGertsch &Mulaik), spider-weaver black (LatrodectusmactansFabricius), and millipedes squad Scutigeromorpha, such as centipede home (house centipede) (Scutigera coleoptrataLinnaeus).

The compounds of this invention also have activity against representatives of the class Nematoda, Cestoda, Trematoda and Acanthocphala, including important from an economic point of view of the representatives of the orders Strongylida, Ascaridida, Oxyurida, Rhabditida, Spirurida, and Enoplida, such as, but not limited to those that are important from an economic point of view of agricultural pests (i.e. nematodes root knot genus Meloidogyne, nematode damage (lesion nematodes) of the genus Pratylenchus, nematodes short root (stubby root nematodes of genus Trichodorus and so on) and pests harmful to the health of animals and humans (i.e., all important from an economic point of view, flukes, tapeworms and roundworms, such asStrongylus vulgarisin the body of a horse,Toxocaracanisin the body of the dog,At contortusin the body of the sheep,Dirofilaria iimnitisLeidy in the body of the dog,Anoplocephala perfollatain the body of a horse,Fasciola hepaticaLinnaeus in the body of some animal, and so on).

The compounds of this invention show particularly high activity against pests of Lepidoptera (e.g.,Alabama argillaceaHübner (scoop),Archips argyrospilaWalker (tortrix),A. rosanaLinnaeus (tortrix European (European leaf roller) and other representatives of the species Archips,Chilo suppressalisWalker (driller trunk rice (rice stem borer),CnaphalocrosismedinalisGuenee (rice moth (rice leaf roller)),Crambus caliginosellusClemens (Ognevka),Crambus teterrellusZincken (Ognevka),Cydia pomonellaLinnaeus (Codling moth),Earias insulanaBoisduval (Sunny ballworm),Earias vittellaFabricius (spotted bollworm),Helicoverpa amigera Hübner (cotton bollworm),Helicoverpa zeaBoddie (boxed worm),Heliothis virescensFabricius (scoop),Herpetogramma licarsisalisWalker (meadow moths),Lobesia botranaDenis & Schiffermüller (moth vine),Pectinqphora gossypiellaSaunders (pink box worm),Phyllocnistis citrellaStainton (citrus mol-miner number),Pieris brassicaeLinnaeus (cabbage butterflies),Pieris rapaeLinnaeus (small butterflies),Plutella xylostellaLinnaeus (cabbage moth),Spodoptera exiguaHübner (beet marching worm (small scoop)),Spodoptera lituraFabricius (tobacco cutworm, cluster caterpillar), Spodoptera frugiperda J. E. Smith (scoop herbal),Trichqplusia niHübner (scoop) andTuta absolutaMeyrick (mol-miner tomato)).

The compounds of this invention are also commercially significant activity against members of the order Homoptera, includingAcyrthisiphon pisumHarris (pea aphid),Aphis craccivoraKoch (black aphids alfalfa),Aphis fabaeScopoli (bean aphid),Aphis gossypiiGlover (cotton aphid),Aphis pomi DeGeer (aphid Codling),Aphis spiraecolaPatch (aphid Tamagawa),Aulacorthum solaniKaltenbach (foxglove aphid),Chaetosiphon fragaefoliiCockerell (strawberry aphid),Diuraphis noxiaKurdjumov/MordviIko (Russian wheat aphid),Dysaphis plantagineaPaaserini (aphid pink),Eriosoma lanigerumHausmann (aphid blood leaf),Hyalopterus pruniGeoffroy (aphids, mealy plum),Lipaphis erysimiKaltenbach (aphid lookupentry),Metopolophium dirrhodumWalker (grain aphid),Macrosipum euphorbiaeThomas (potato aphid is), Myzus persicaeSulzer (peach aphid),Nasonovia ribisnigriMosley (lettuce aphid), Pemphigus spp. (root aphids and gallarraga aphid),Rhopalosiphum maidisFitch (aphid corn leaf),Rhopalosiphum padiLinnaeus (bird cherry-oat aphid),Schizaphis graminumRondani (cereal aphid common),Sitobion avenaeFabricius (cereal aphid),Therioaphis maculataBuckton (spotted alfalfa aphid),Toxoptera aurantiiBoyer Fonscolombe (tea aphid) andToxoptera citricidaKirkaldy (citrus aphid);Adelgesspp. (Hermes);Phylloxera devastatrixPergande (phylloxera Hickory);Bemisia tabaciGennadius (whiteflies Batalova),Bemisia argentifoliiBellows &Perring (silverleaf whitefly),Dialeurodes citriAshmead (citrus whitefly) andTrialeurodes vaporariorumWestwood (greenhouse whitefly);Empoasca fabaeHarris (Cicada potato),Laodelphax striatellusFallen (smaller brown planthopper),Macrolestes quadrilineatusForbes (aster leafhopper),Nephotettix cinticepsUhler (green leafhopper),Nephotettix nigropictusStal (Cicada rice (rice leafhopper)),Nilaparvata lugensStel (browm planthopper),Peregrinus maidisAshmead (corn planthopper),Sogatella furciferaHorvath (white-backed planthopper),SogatodesorizicolaMuir (rice delphacid),Typhtocyba pomariaMcAtee (Cicada Apple),Erythroneouraspp. (Cicada grape);Magicidada septendecimLinnaeus (periodical cicada);Icerya purchasiMaskell (mealybug Australian grooved),Quadraspidiotus perniciosusComstock (San Jose scala);Planococcus citriRisso (mealybug grape powdery);Pseudococcusspp. (community scale);Cacopsilla pyricolaFoerster (medenica pear),Trioza diospyriAshmead (listblock Jurmala).

Data connect the deposits also have activity against members of the order Hemiptera (Heteroptera), includingAcrosternum hilareSay (green activist),Anasa tristisDe Geer (bug-rombout sad),Blissus leucopterusleucopterusSay (bug dall),Corythuca gossypiiFabricius (bug-lace cotton),Cyrtopeltis modestaDistant (tomato bug),Dysdercus suturellusHerrish-Schaffer (Krasnogo cotton),Euchistus servusSay (bug-activist brown),Euchistus variolariusPalisot de Beuavois (bug-activist adenopathy),Graptosthetusspp. (community bugs-najemnikov),Leptoglossus corculusSay (bug-crevic pine seeds),Lygus lineolarisPalisot de Beuavois (klopik meadow),Nesara viridulaLinnaeus (bug cotton gardening);Oebalus pugnaxFabricius (bug-activist rice),Oncopeltus fasciatusDallas (bug Euphorbiaceae),Pseudatomoscelis seriatusReuter (Slepak cotton).

Other orders of insects targeted by the compounds of the present invention, are insects squad Thysanoptera (thrips) (for example,Frankliniella occidentallisPergande (Western flower thrips),Scirthothrips citriMoulton (citrus thrips),Sericothrips variabilisBeach trips soy) andThrips tabaciLindenman (thrips), and the order Coleoptera (Beetles) (for example,Leptinotarsa decemlineataSay (Colorado potato beetle),Epilachna varivestisMulsant (bean weevil Mexican) and larvae of click beetles of the genusAgriotes,AthousorLimonius).

Compounds of the present invention can also be mixed with one or more other biologically active compounds or agents including, and tacticity, fungicides, nematicides, bactericides, acaricides, growth regulators, such as stimulants education roots, chemical sterilizing agents, Poluchenie connection, repellents, attractant, pheromones, stimulants nutrition, other biologically active compounds or entomopathogenic bacteria, virus or fungi to obtain multicomponent pesticide with a wider range of applications in agriculture. Thus, the compositions of the present invention may also contain biologically effective amount of at least one additional biologically active compound or agent. Examples of such compounds or agents with which compounds of the present invention may be introduced into the drug, are

insecticides such as abamectin, Arafat, acetamiprid, avermectin, azadirachtin, azinphos-methyl, bifenthrin, bifenazate, buprofezin, carbofuran, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clothianidin, cyfluthrin, beta-cyfluthrin, cigalotrin, lambda cigalotrin, cypermethrin, cyromazine, Delta-methrin, diafenthiuron, diazinon, diflubenzuron, dimethoate, giovanola, emamectin, endosulfan, esfenvalerate, ethiprole, fanatical, fenoxycarb, fenpropathrin, fenpyroximate, fenvalerate, fipronil, flonicamid, flucythrinate, Tau-flowline is, flufenoksuron, fonofos, halogenated, hexaflumuron, Imidacloprid, indoxacarb, isofenphos, lufenuron, Malathion, metaldehyde, metamidophos, methidathion, methomyl, methoprene, Methoxychlor, monocrotophos, methoxyfenozide, nithiazine, novaluron, oxamyl, parathion, parathion-methyl, permethrin, Fort, fozalon, phosmet, phosphamidon, pirimicarb, profenofos, pymetrozine, pyridalyl, pyriproxifen, rotenon, spinosad, sulprofos, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb, thiosulfat-sodium, tralomethrin, trichlorfon and triflumuron;

fungicides, such as acibenzolar, AZOXYSTROBIN, benomyl, blasticidin-S, Bordeaux mixture (rejonowy copper sulphate), bromuconazole, cropropamide, captafol, Captan, carbendazim, chloroneb, CHLOROTHALONIL, copper oxychloride, copper salt, cyflufenamid, having cymoxanil, tsyprokonazolu, cyprodinil, (S) - for 3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide (RH 7821), diclocil (S-2900), declomycin, dicloran, difenoconazol, (S)for 3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3-(phenylamino)-4H-imidazol-4-one (RP 407213), dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, Dodin, edifenphos, epoxiconazol, famoxadone, finanical, fenarimol, fenbuconazole, paneramic (SZX0722), fenpiclonil, fenpropidin, fenpropimorph, acetate fentin, hydroxide fentin, fluazinam, fludyoksonil flamethower (RPA 43397), plugincontrol, flusilazol, flutolanil, flutriafol, folpet, fosetyl-aluminum, parallaxis, parameter (S-82658), hexaconazole, ipconazole, iprobenfos, iprodion, isoprothiolane, kasugamycin, kresoxim-methyl, MANCOZEB, MANEB, mefenoxam, mepronil, metalaxyl, metconazole, metamyosyn/phenominalrose (SSF-126), myclobutanil, neo-Asotin (metanational iron (3)), oxadixyl, penconazole, pencycuron, provenzal, prochloraz, propamocarb, propiconazol, pirivenas, pyraclostrobin, Pyrimethanil, pyroxylin, jenoxifen, spiroxamine, sulfur, tebuconazole, tetraconazole, thiabendazol, leflunomid, thiophanate-methyl, thiram, tadini, triadimefon, triadimenol, tricyclazole, Trifloxystrobin, triticonazole, validamycin and vinclozolin;

the nematicides such as aldicarb, oxamyl and fenamiphos;

bactericides such as streptomycin;

acaricides, such as amitraz, chinomethionat, Chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, the oxide fenbutatin, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad and

biological agents, such asBacillus thuringiensisincluding the speciesaizawaiandkurstakiDelta-endotoxinBacillus thuringiensis, baculovirus, and entomopathogenic bacteria, viruses and fungi.

The compounds used in accordance with the present invention and their compositions can be applied to t Engannim plants for protein expression, toxic to invertebrate pests (such as toxinBacillus thuringiensis). Exogenous compounds used for combating invertebrate pests, and their compositions can have a synergistic effect with protein, expressing the toxin.

General guidance on the specified protective agrotechnical means isThe Pesticide Manual, 12th Edition,C.D.S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2000.

Preferred insecticides and acaricides for mixing with compounds of this invention include pyrethroids such as cypermethrin, cigalotrin, cyfluthrin, beta-cyfluthrin, esfenvalerate, fenvalerate and tralomethrin; carbamates, such as fanatical, methomyl, oxamyl and thiodicarb; neo-nicotinoid, such as clothianidin, Imidacloprid and thiacloprid; blockers of neuronal sodium channels, such as indoxacarb, insecticidal macrocyclic lactones such as spinosad, abamectin, avermectin and emamectin; antagonists γ-aminobutyric acid (GABA), such as endosulfan, ethiprole and fipronil; urea possessing insecticidal activity, such as flufenoxuron and triflumuron; juvenile hormone mimetics, such as giovanola and pyriproxyfen; pymetrozine and amitraz. Preferred biological agents for mixing with compounds of this invention areBacillusthuringiensis and Delta-endotoxinBacillus thuringiensisas well as natural and transgenic viral insecticides, including members of the family Baculoviridae, and fungi-entomophages.

The most preferred mixtures are a mixture of compounds of the present invention and cyhalothrin; a mixture of compounds of the present invention and beta-spraying with cyfluthrin; a mixture of compounds of the present invention and esfenvalerate; a mixture of compounds of the present invention and methomyl; a mixture of compounds of the present invention and Imidacloprid; a mixture of compounds of the present invention and thiacloprid; a mixture of compounds of the present invention and indoxacarb; a mixture of compounds of the present invention and abamectin; a mixture of compounds of the present invention and endosulfan; a mixture of compounds of the present invention and ethiprole; a mixture of compounds of the present invention and fipronil; a mixture of compounds of the present invention and flufenoxuron; a mixture of compounds of the present invention, pyriproxyfen; a mixture of compounds of the present inventions and pymetrozine; a mixture of compounds of the present invention and amitraz; a mixture of compounds of the present invention andBacillus thuringiensisand the mixture of the compounds of the present invention, and Delta-endotoxinBacillus thuringiensis.

In some examples, the combination with other compounds or agents exhibiting pesticidal activity against the AI invertebrate pests will be particularly preimuschestvami for sustainable species. Thus, the compositions of this invention may additionally include a biologically effective amount of at least one additional compounds with pesticidal activity against invertebrate pests, or tools with a similar spectrum of control but a different mechanism of action. The contacting of plants genetically modified for the expression of compounds with protective action (e.g., protein) or growing plants with a biologically effective amount of compounds of the invention can also provide a wider range of protection of plants and be pre-emptive to adjust the resistance.

Invertebrate pests suppressed in agricultural and non-agricultural applications applying one or more compounds used in accordance with this invention, an effective amount on the habitat of the pests, including agricultural and/or non-agricultural hotbed of infection, the area that should be protected, or directly on the pests to be suppressed. Therefore, the invention further includes a method of combating invertebrate pests in selskohozyaistvenny and/or non-agricultural applications, comprising contacting the invertebrate or its environment with a biologically effective amount of one or more compounds of the present invention, with a composition comprising at least one such compound, or composition comprising at least one such compound and an effective amount of at least one additional biologically active compound or agent. Examples of suitable compositions comprising a compound of this invention and at least one additional biologically active compound or agent, include granular compositions, in which the additional biologically active compound is in the same granule as the connection of the present invention, or in a separate granules.

Preferred method of contact is by spraying. Alternative granulated composition comprising a compound of this invention can be applied to the foliage of plants or to the soil. The compounds used in accordance with this invention, also effectively absorbed by plants by contacting plants with a composition comprising the compound used in accordance with this invention, when the irrigation liquid drug, making granulated drug in the soil, processing mailbox in PITOMNIK the e or the immersion of transplanted plants. The compounds are also effective when topically applying the composition comprising the compound used in accordance with this invention, on the islet. Other methods of contact include the application of the compounds or compositions of the present invention direct or residual spraying, air spraying, in the form of gels, coatings seeds, microencapsulation, system absorption, as baits, with food (eartags), in the form of a bolus in the form of mists, okurimono, aerosols, powders, and other Compounds used in accordance with this invention, can be impregnated into materials in the manufacture of devices for combating invertebrate pests (for example, insectocutor).

The compounds used in accordance with this invention, it is possible to enter in baits that are eaten by invertebrates, or inside devices such as traps, etc. Granules or baits, comprising 0.01 to 5% of the active ingredient, 0.05 to 10% agent that retains moisture, and 40-99% of flora, effective against soil insects at very low doses, particularly in the doses of the active ingredient, which are lethal when eating, and not by direct contact.

The compounds used in accordance with this invention, can be applied in pure form, but the most common application b is det drug, comprising one or more compounds with suitable carriers, diluents and surfactants, and possibly in combination with food, depending on the intended end use. The preferred method of applying includes spraying the aqueous dispersion of the purified oil solution of the compounds. Combination with spray oil spray oil concentrates, distributors-stickers, adjuvants, other solvents and synergists, such as piperonylbutoxide, often increases the efficiency of the connection.

The applied dose required for effective suppression (i.e. the "biologically effective amount") will depend on such factors as type bespozvonochnykh subject to suppression, the life cycle of the pest, stage of development, size, location, time of year, plant or animal host, feeding behavior, mating behavior, environment humidity, temperature, etc. In the normal conditions of the applied dose of approximately 0.01 to 2 kg of active ingredient per hectare are sufficient to suppress pests in agricultural ecosystems, but may be sufficient and 0.0001 kg/hectare, or, at most, you may need 8 kg/ha. For non-agricultural applications effective dose will be in the interval is from about 1.0 to 50 mg/sqm, but it may be enough, and 0.1 mg/sq m, or may take 150 mg/sqm Qualified in this field specialist can easily identify biologically effective amount necessary for the desired level of suppression of invertebrate pests.

The following tests on the biological activity of the compounds of this invention show the effectiveness of the methods of the present invention, is not limited to these species. The description of the compounds are presented in tables A-D. In the tables the following abbreviations are used: i means ISO, Me means methyl, Ph is phenyl, and Pr represents a propyl (respectively, i-Pr represents isopropyl). In tables b and C shows a snippet of R1-R2that the left end of the fragment is attached to the location of R1and the right end of the fragment is attached to the location of R2. The abbreviation "Etc." means "example", and the following number indicates in which example the compound obtained.

Table a
ConnectionR4bR2R5VTPL (°C)
1NCH(Me)CH2Cl CF3CH129-131
2 (PR)Ni-PrCF3CH133-135
3NMeCF3CH158-163
4 (App.1)Ni-PrCF3N175-176
5Bri-PrCF3N173-174
6BrpropargylCF3N187-190
7Cli-PrBrN207-209
8ClMeBrN234-236
9Cli-PrCF3N165-166
10ClMeCF3N181-182
11Cli-PrClN182-183
12Hi-PrBrN174-175

Table B


ConnectionR4aR4bR1-R2R5VTPL(°C)
13 (PR)ClCl-CH2CH2-CF3N*
14ClCl-CH2CH2C(=O)-CF3N*
15ClCl-CH=C(CH3)-CF3N*
16ClCl-C(CH3)=CH-CF3N*
* Data1H NMR are shown in table D

Table With
ConnectionR4aR4bR1-R2JTPL(°C)
17H H-CH2CH2-2,4-Cl2-Ph
18ClCl-CH=N3-Me-Ph
19ClCl-CH=N4-Cl-Ph

Table D
Connection1H NMR data (CDCl solution3,- unless otherwise stated)
13δ and 8.4 (d, 1H), 7,9 (m, 2H), 7,45 (d, 1H), and 7.4 (DD, 1H), and 7.1 (s, 1H), 4,4 (m, 2H), from 4.3 to 4.2 (m, 2H).
14δ 8,5 an 8.4 (d, 1H), and 8.4 to 8.3 (DD, 1H), 8,0 was 7.9 (DD, 1H), and 7.6-7.5 (d, 1H), and 7.4 (m, 2H), to 7.09 (s, 1H), to 4.52 (t, 2H), 2,78 (t, 2H), 2.13 and (s, 3H).
15δ to 8.41 (d, 1H), 8,39 (DD, 1H), of 7.90 (DD, 1H), 7,81 (kV, 1H), to 7.59 (d, 1H), 7,46 (s, 1H), 7,41 (DD, 1H), 2.57 m (d, 3H).
16δ 8,42 (d, 1H), 8,09 (DD, 1H), of 7.90 (DD, 1H), 7.62mm (d, 1H), 7,46 (m, 1H), 7,27 (DD, 1H), 7,05 (s, 1H), 2,33 (d, 3H).

The INDEX TABLE E
ConnectionR4bR2R7VTPL (°)
20CNMe BrN250-250
21CNMeClN234-235
22CNHCF3N167-168

BIOLOGICAL EXAMPLES of the INVENTION

TEST AND

To evaluate the suppression of the cabbage moth (Phutella xylostella) use experimental block consisting of a small open container, inside of which is placed (12-14)-day radish plants. Plants pre-infect 10-15 newborn larvae on the fragment of the nutrient medium of the insect using a core sampler for separation of the sample from a sheet of solidified nutrient mass of insects with lots of grown on him larvae and transfer of the sample containing the larvae and their food, in the experimental block. Larvae move to the pilot plant, when a sample of the nutrient mass dries.

Compound in the form of preparations prepared using a solution containing 10% acetone, 90% water and 300 hours/million nonionic surface-active drug X-77®Spreader Lo-Foam Formula that includes alkalinisation, free fatty acids, glycols and isopropanol (Loveland Industries, Inc.), if not stated otherwise. Connection in the form of such drugs used in the form of 1 ml of liquid through the sprayer is th nozzle SUJ2 normal configuration 1/8 JJ (Spraying systems Co.), located at a distance of 1.27 cm (0.5 inch) from the top of each experimental block. All experimental compounds in this experience is sprayed at a concentration of 250 hours/million (or less) and the above processing is repeated three times. After spraying with the preparation of the test compounds each experimental block allow to dry for 1 hour and then the upper part is closed with black lattice cover. Experimental blocks was incubated for 6 days in a growth chamber at 25°C and relative humidity of 70%. Then visually assess the damage to the plants for insects are food.

Of the tested compounds is very good levels of protection of plants (damage plants, which use insects as food is 20% or less) in the doses used in the trial showed the following connections: 1*, 2*, 3*, 4*, 5*, 6*, 7**, 8**, 9**, 10**, 11**, 12**, 13**, 14, 15*, 16*, 20**, 21** and 22**.

TEST

To evaluate the suppression of the "war of the worms" (fall armyworms) (Spodoptera frugiperda) use experimental block consisting of a small open container placed inside (4-5)-day maize plants. Plants pre-infect 10-15 larvae age 1 day on a piece of food of the insect using a core sampler, as described for test A.

Prepare for a drug test connection and put priscian who eat at a concentration of 250 hours/million (or less)as described for test A. the above processing is repeated three times. After spraying pilot blocks is kept in a growth chamber and then visually assess the damage to the plants used by insects as food, as described for test A.

Of the tested compounds is very good levels of protection of plants (damage plants, which use insects as food is 20% or less) in the doses used in the trial showed the following connections: 1*, 2*, 3*, 4*, 5*, 6*, 7**, 8**, 9**, 10**, 11**, 12**, 13, 14, 20**, 21** and 22**.

TEST

To assess the suppression of moths (Heliothis virescens) use experimental block consisting of a small open container placed inside (6-7)-day maize plants. Plants pre-infect larvae at the age of 2 days on a fragment of a nutrient medium of the insect using a core sampler, as described for test A.

Prepare for a drug test connection and applied by spraying at a concentration of 250 hours/million (or less)as described for test A. the above processing is repeated three times. After spraying pilot blocks is kept in a growth chamber and then visually assess the damage to the plants used by insects as food, as described for test A.

Of the tested compounds is very good levels of protection the s plants (damage plants, which is used by insects as food is 20% or less) in the doses used in the trial showed the following connections: 1*, 2*, 3*, 4*, 5*, 6*, 7*, 8**, 9**, 10**, 11**, 12**.

TEST D

To assess the suppression of beet military worm (beet armyworm) (Spodoptera exiqua) use experimental block consisting of a small open container placed inside (4-5)-day maize plants. Plants pre-infect 10-15 larvae age 2 days on a fragment of a nutrient medium of the insect using a core sampler, as described for test A.

Prepare for a drug test connection and applied by spraying at a concentration of 250 hours/million (or less)as described in test A. the above processing is repeated three times. After spraying pilot blocks is kept in a growth chamber and then visually assess the damage to the plants used by insects as food, as described for test A.

Of the tested compounds is very good levels of protection of plants (damage plants, which use insects as food is 20% or less) in the doses used in the trial showed the following connections: 1*, 2*, 3*, 4*, 5*, 6*, 7**, 8**, 9**, 10**, 11**, 12**.

* The compound was tested at a concentration of 50 PM/million

** The compound was tested at a concentration of 10 hours/million

1. The connection is of the formula I

where is O or NR1;

J represents a 5-membered heteroaromatic ring, which is a group J-1, optional replaced 1-2 R5,

Q is NR5;

X, Y and Z each independently represents N, CH or CR5;

In is On and

R2represents N or C1-C6alkyl, optionally substituted by one halogen atom, or a C2-C6quinil; or

In represents NR1and

R1and R2taken together form a linking chain of 2-3 members, including at least one carbon atom, optionally containing one carbon atom of the form C(=O), optionally substituted R3;

R3independently represents C1-C2alkyl;

each R4independently represents H, C1-C6alkyl, halogen or CN;

each R5independently represents C1-C6halogenated or halogen, or

each R5independently represents phenyl or pyridinyl, each ring substituted with one R6;

each R6independently represents halogen and

n represents the integer 1 or 2.

2. The compound according to claim 1, where

In performance, is made by and About

one R4attached to the phenyl ring in position 2 and the specified R4is1-C4alkyl.

3. The compound according to claim 2, where

J-1, substituted 2 R5is J-6

V represents N, CH;

R6ais R6;

R6represents halogen and

R7represents C1-C6halogenated or halogen.

4. The compound according to claim 3, where

R2represents C1-C4alkyl, optionally substituted by a halogen atom;

one of R4attached to the phenyl ring in position 2 and the specified R4is CH3;

the second R4represents H, Cl or Br and

R7is CF3or halogen.

5. The compound according to claim 4, selected from the group including:

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-ilidene]methanamine,

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[6-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]methanamine,

N-[6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifter ethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-8-methyl-4H-3,1-benzoxazin-4-ilidene]-2-propanamine,

N-[2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-cyano-8-methyl-4H-3,1-benzoxazin-4-ilidene]methanamine and

N-[2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6-cyano-8-methyl-4H-3,1-benzoxazin-4-ilidene]methanamine.

6. The compound according to claim 1, where

J-1, substituted with 1-2 R5is J-6

In represents NR1and

R1and R2taken together form a linking chain of 2-3 members, including at least one carbon atom, optionally containing one carbon atom of the form C(=O), optionally substituted R3;

R3independently represents C1-C2alkyl;

one R4attached to the phenyl ring in position 2 and the specified R4is Cl and the second R4represents Cl;

V is N;

R6ais R6;

R6represents halogen and

R7represents C1-C6halogenated.

7. The connection according to claim 6, which is a

7,9-dichloro-5-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-yl]-2,3-dihydro is idazo[1,2-C]hinzelin.

8. Composition for combating insects comprising a biologically effective amount of the compounds of formula I according to claim 1 and at least one additional component selected from the group comprising surfactants, solid diluents and liquid diluents.

9. The composition of claim 8, where the composition further includes at least one additional biological compound or agent.

10. A method of combating insects comprising contacting bespozvonochnykh pest or its habitat with a composition of claim 8 or 9.

11. A method of combating insects comprising contacting the pests or their habitat environment with a biologically effective amount of a compound according to claim 1.



 

Same patents:

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to novel oxazolidinones of the general formula (I): , their pharmaceutically acceptable salts, hydrates and salt hydrates that inhibit factor Xa selectively and possess anti-thrombosis effect. Also, invention relates to a method for synthesis of these compounds (variants) and using the known substituted oxazolidinones of the general formula (A): as agent inhibiting factor Xa selectively and possessing anti-thrombosis effect, and to a medicinal agent based on at least one compound of the formula (I) or at least one compound of the general formula (A). Values of substitutes R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are given in the invention claim.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds and agent.

10 cl, 2 tbl, 252 ex

FIELD: chemistry of heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (1): and their salts wherein values R1, k, Ar, n, j, Y, R and R2 are determined in the invention claim. Novel compounds are able to modulate activity of chemokine receptors. Also, invention relates to using indicated compounds for treatment of human immunodeficiency virus or feline immunodeficiency virus and to a pharmaceutical composition based on thereof.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

16 cl, 100 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivative compound of carboxylic acid represented by the formula (I): , wherein each X and Y represents independently (C1-C4)-alkylene; Z means -O-; each R1, R2, R3 and R4 means independently hydrogen atom or (C1-C8)-alkyl; R5 means (C2-C8)-alkenyl; A means -O- or -S-; D means D1, D2, D3, D4 or D5 wherein D1 means (C1-C8)-alkyl; D2 means compound of the formula: wherein ring 1 represents saturated 6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom chosen from oxygen, sulfur and nitrogen atoms; D3 means compound of the formula: wherein ring 2 represents (1) completely saturated (C3-C10)-monocarboxylic aryl, or (2) optionally saturated 5-membered monoheteroaryl comprising 3 atoms chosen from nitrogen and sulfur atoms, or completely saturated 6-membered monoheteroaryl comprising 1 heteroatom representing oxygen atom; D4 means compound of the formula: ; D5 means compound of the formula: ; R6 represents (1) hydrogen atom, (2) (C1-C8)-alkyl, (3) -NR7R8 wherein R7 or R8 represent hydrogen atom or (C1-C8)-alkyl, or R7 and R8 taken in common with nitrogen atom to which they are added form saturated 5-6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom representing oxygen atom; E means -CH or nitrogen atom; m means a whole number 1-3, or its nontoxic salt. Invention relates to a regulator activated by peroxisome proliferator receptor, agent used in prophylaxis and/or treatment of diseases associated with metabolism disorders, such as diabetes mellitus, obesity, syndrome X, hypercholesterolemia or hyperlipoproteinemia, hyperlipidemia, atherosclerosis, hypertension, diseases coursing with circulation disorder, overeating or heart ischemic disease, and to an agent that increases cholesterol level associated with HDL, reduces cholesterol level associated with LDL and/or VLDL, eliminates risk factor in development of diabetes mellitus and/or syndrome X and comprising a compound represented by the formula (I) or its nontoxic salt as an active component and a carrier, excipient or solvent optionally. Invention proposes derivative compounds of carboxylic acid possessing the modulating activity with respect to peroxisome proliferator receptor (PPAR).

EFFECT: valuable medicinal properties of compounds.

15 cl, 5 tbl, 48 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds represented by the general formula (I): and their pharmaceutically acceptable salts and esters possessing agonistic activity with respect to peroxisome proliferator receptors PPARα and/or PPARγ, to a pharmaceutical composition based on thereof and their using for preparing medicines wherein R1 means thiophenyl or phenyl optionally substituted with from one to three substitutes chosen independently from halogen atom, (C1-C8)-alkoxy-group, (C1-C8)-alkyl and (C1-C8)-alkyl substituted with one-three halogen atoms; R2 means hydrogen atom or (C1-C8)-alkyl; R3 means phenoxy-, (C2-C8)-alkenyloxy- or (C1-C8)-alkoxy-group; R4 means hydrogen atom or (C1-C8)-alkyl wherein one of substitutes R5 and R6 means compound of the formula and another one means hydrogen atom and wherein the bond between carbon atoms Ca and Cb means a carbon-carbon simple or double bond; R7 means hydrogen atom or (C1-C8)-alkyl; R8 means hydrogen atom or (C1-C8)-alkyl being any of A and A1 means nitrogen atom and another means oxygen or sulfur atom; n means 1, 2 or 3.

EFFECT: valuable medicinal properties of compound and pharmaceutical composition.

30 cl, 1 tbl, 14 sch, 86 ex

FIELD: organic chemistry, chemical technology, insecticides.

SUBSTANCE: invention relates to derivatives of N-heteroaryl-4-(halogenalkyl)nicotinamide represented by the general formula (I): wherein R represents (C1-C6)-alkyl group that can be substituted with one or some halogen atoms; R1 represents hydrogen atom, (C1-C6)-alkyl group that can be substituted with one or some substituted chosen from group of substitutes A, (C2-C6)-alkenyl group or acyl group; X represents group of the formula -C-R2 or nitrogen atom; each among R2 and R3 represents independently hydrogen atom, halogen atom, (C1-C6)-alkyl group that can be substituted with one or some substitutes chosen from group of substitutes A, (C3-C7)-cycloalkyl group, (C2-C6)-alkenyl group, (C3-C7)-cycloalkenyl group, formyl group, group of the formula: -CH=NOR4 (wherein R4 represents hydrogen atom or (C1-C6)-alkyl group, cyano-group, phenyl group that can be substituted with one or some substitutes chosen from group of substitutes B, 5- or 6-membered heterocyclic group (heterocycle comprising 1-2 heteroatoms that are similar and chosen from nitrogen atom), (C1-C6)-alkoxy-group, (C1-C6)-alkylthio-group or phenoxy-group. The group of substitutes A represents group consisting of halogen atom, (C1-C6)-alkoxy-group, (C1-C6)-alkylthio-group, cyano-group and phenyl group. The group of substitutes B represents group consisting of halogen atom, (C1-C6)-alkyl group that can be substituted with one or some substitutes chosen from above given group of substitutes A, (C1-C6)-alkoxy-group that can be substituted with one or some substitutes chosen from above given group of substitutes A, or its salt. Also, invention relates to insecticide comprising a derivative of N-heteroaryl-4-(halogenalkyl)nicotinamide or its salt as an active component and a carrier optionally. Also, invention relates to a method for synthesis of derivative of N-heteroaryl-4-(halogenalkyl)nicotinamide. Invention provides synthesis of derivatives of N-heteroaryl-4-(halogenalkyl)nicotinamide possessing the high insecticide activity.

EFFECT: improved method of synthesis, valuable properties of derivatives.

18 cl, 3 tbl, 91 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compound represented by the structural formula: or its pharmaceutically acceptable salt wherein Z represents -(CH2)n-; double dotted line represents a double bond; n = 0-2; R1 and R2 are chosen independently from the group comprising hydrogen atom (H), alkyl with 1-6 carbon atoms; R3 means H, hydroxy-, alkoxy-group with 1-6 carbon atoms, -C(O)OR17 or alkyl with 1-6 carbon atoms; Het means monocyclic heteroaromatic group consisting of 6 atoms and comprising 5 carbon atoms and one heteroatom chosen from nitrogen atom (N) and wherein Het is bound through ring carbon atom and wherein Het-group has one substitute W chosen independently from the group comprising bromine atom (Br), heterocycloalkyl representing group consisting of 4 carbon atoms and one heteroatom chosen from N; heterocycloalkyl representing group consisting of 4 carbon atoms and one heteroatom chosen from N substituted with OH-substituted alkyl with 1-6 carbon atoms or =O; R21 -aryl-NH-; -C(=NOR17)R18; R21-aryl; R41-heteroaryl representing group consisting of 5-6 atoms comprising 3-5 carbon atoms and 1-4 heteroatoms chosen independently from the group: N, S and O; R8 and R10 are chosen independently from group comprising R1; R9 means H; R11 is chosen from group comprising R1 and -CH2OBn wherein Bn means benzyl; B means -(CH2)n4CR12=CR12a(CH2)n5; n4 and n5 mean independently 0; R12 and R12a are chosen independently from group comprising H, alkyl with 1-6 carbon atoms; X means -O-; Y means =O; R15 is absent as far as double dotted line mean a simple bond; R16 means lower alkyl with 1-6 carbon atoms; R17 and R18 are chosen independently from group comprising H, alkyl with 1-6 carbon atoms; R21 means 1-3 substituted chosen independently from group comprising hydrogen atom, -CN, -CF3, halogen atom, alkyl with 1-6 carbon atoms and so on; R22 is chosen independently from group comprising hydrogen atom; R24-alkyl with 1-10 carbon atoms; R25-aryl and so on; R23 is chosen independently from group comprising hydrogen atom, R24-alkyl with 1-10 carbon atoms, R25-aryl and -CH2OBn; R24 means 1-3 substitutes chosen independently from group comprising hydrogen atom, halogen atom, -OH, alkoxy-group with 1-6 carbon atoms; R25 means hydrogen atom; R41 means 1-4 substitutes chosen independently from group comprising hydrogen atom, alkyl with 1-6 carbon atoms and so on. Also, invention relates to a pharmaceutical composition possessing the inhibitory activity with respect to receptors activated by protease and comprising the effective dose of derivative of nor-seco-chimbacine of the formula (I) and a pharmaceutically acceptable excipient. Also, invention relates to methods for inhibition of thrombin and cannabinoid receptors comprising administration in mammal derivative of nor-seco-chimbacine of the formula (I) in the effective dose as active substance. Invention provides derivatives of nor-seco-chimbacine as antagonists of thrombin receptors.

EFFECT: valuable medicinal and biological properties of compounds and pharmaceutical composition.

8 cl, 1 tbl, 18 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of compound of the formula (1): wherein Y means -O-, -S- or -N(R2)- wherein R2 means hydrogen atom, (C1-C10)-alkyl or aralkyl; Z means 2,5-furanyl, 2,5-thiophenyl, 4,4'-stilbenyl or 1,2-ethyleneyl residue; R1 means hydrogen or halogen atom, (C1-C10)-alkyl, (C1-C10)-alkoxy-group, cyano-group, -COOM or -SO3M wherein M means hydrogen atom or alkaline or alkaline-earth metal atom. Method for synthesis involves carrying out the reaction of compound of the formula (2): with dicarboxylic acid of the formula: HOOC-Z-COOH (3) or with it ester wherein Y, Z and R1 have values given above in N-methylpyrrolidone or N,N-dimethylacetamide medium in the presence of an acid catalyst and optionally in the presence of an accessory solvent able to remove water from the reaction mixture.

EFFECT: improved method of synthesis.

11 cl, 7 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of sulfonamide of the general formula (I): wherein A means a substitute chosen from 5- or 6-membered heteroaromatic ring comprising 1 or 2 heteroatoms chosen from oxygen (O), nitrogen (N) or sulfur (S) optionally substituted with 1 or 2 halogen atoms, (C1-C4)-alkyl or phenyl radical, or 5- or 6-membered heteroaryl radical comprising 1 or 2 atoms of O, N or S; bicyclic heteroaromatic ring comprising from 1 to 3 heteroatoms chosen from O, N or S and optionally substituted with 1 or 2 halogen atoms or (C1-C4)-alkyl; R1 means hydrogen atom (H), (C1-C4)-alkyl, benzyl; n means 0, 1, 2, 3 or 4; R2 means -NRR5 or the group of the formula: wherein a dotted line means optional chemical bond; R, R4 and R5 mean independently H or (C1-C4)-alkyl; or one of its physiologically acceptable salts. Compounds of the formula (1) possess antagonistic activity with respect to serotonin HT6-receptors that allows their using in pharmaceutical composition and for preparing a medicament.

EFFECT: valuable medicinal properties of derivatives and pharmaceutical composition.

10 cl, 2 tbl, 7 ex

FIELD: organic chemistry, anti-microbial preparations.

SUBSTANCE: invention relates to compounds useful as anti-microbial agents. Claimed compounds are effective against to certain human and animal pathogens, including Gram-positive aerobic bacteria such as multi-resistant staphylococcus, streptococcus and enterococcus, as well as anaerobic organisms such as species Bacterioides spp. and Clostridia spp., and acid resistant organisms such as Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium spp.

EFFECT: new anti-microbial agents.

2 ex, 5 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a novel class of 5-membered heterocyclic compounds of the general formula (I): or cosmetically acceptable salts. Invention describes a compound represented by the formula (I) and its pharmaceutically or cosmetically acceptable salt wherein R1 is chosen from linear or branched (C1-C12)-alkyl, (C3-C7)-cycloalkyl, phenyl, naphthyl, C3-, C4-, C5- or C8-heteroaryl wherein one or some heteroatoms when they present are chosen independently from oxygen (O), nitrogen (N) or sulfur (S) atom and substituted optionally wherein substitutes are chosen from the first group comprising halogen atom, hydroxy0, nitro-, cyano-, amino- oxo-group and oxime, or from the second group comprising linear or branched (C1-C8)-alkyl wherein a substitute from indicated second group is optionally substituted with R10, or wherein heteroaryl is substituted with -CH2-C(O)-2-thienyl; Y is absent or chosen from the group consisting of (C1-C12)-alkyl-Z or (C2-C8)-alkyl wherein Z is chosen from sulfur, oxygen or nitrogen atom; A and B are chosen independently from nitrogen atom (N), -NH, -NR6, sulfur, oxygen atom to form heteroaromatic ring system; R2, R3 and R4 are chosen independently from the first group comprising hydrogen, halogen atom, or R3 and R4 form phenyl ring in adjacent positions; R5 is absent or chosen from the group comprising -CH2-phenyl, -CH2(CO)R7, -CH2(CO)NHR8 and -CH2(CO)NR8R9 that are substituted optionally with R10; R6, R7, R8 and R are chosen independently from the group comprising linear or branched (C1-C8)-alkyl, (C3-C7)-cycloalkyl, C5-heterocycloalkyl, benzylpiperidinyl, phenyl, naphthyl, heteroaryl, alkylheteroaryl, adamantyl, or R8 and R9 form piperidine ring, and R means 3,4-ethylenedioxyphenyl wherein substitutes in indicated group are substituted optionally with R10, and heteroaryl means C3-, C4-, C5- or C8-heteroaryl wherein one or some heteroatom when they present are chosen independently from O, N or S; R10 is chosen from halogen atom, hydroxy-, nitro-, cyano-, amino-, oxo-group, perhalogenalkyl-(C1-C6) or oxime; X means halide ion under condition that when groups/substitutes present at the same or at adjacent carbon or nitrogen atoms then can form optionally 5-, 6- or 7-membered ring optionally containing one o some double bonds and containing optionally one or some heteroatoms chosen from O, N or S. Also, invention describes a method for synthesis of these compounds, their therapeutic and cosmetic using, in particular, in regulation of age and diabetic vascular complications. Proposed compounds show effect based on the triple effect as agent destroying AGE (terminal products of enhanced glycosylation), inhibitors of AGE and scavengers of free radicals that do their suitable in different therapeutic and cosmetic using. Also, invention relates to pharmaceutical and cosmetic compositions comprising these compounds and to methods for treatment of diseases caused by accumulation of AGE and/or free radicals in body cells. Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable medicinal properties of compounds.

73 cl, 4 tbl, 63 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivative compound of carboxylic acid represented by the formula (I): , wherein each X and Y represents independently (C1-C4)-alkylene; Z means -O-; each R1, R2, R3 and R4 means independently hydrogen atom or (C1-C8)-alkyl; R5 means (C2-C8)-alkenyl; A means -O- or -S-; D means D1, D2, D3, D4 or D5 wherein D1 means (C1-C8)-alkyl; D2 means compound of the formula: wherein ring 1 represents saturated 6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom chosen from oxygen, sulfur and nitrogen atoms; D3 means compound of the formula: wherein ring 2 represents (1) completely saturated (C3-C10)-monocarboxylic aryl, or (2) optionally saturated 5-membered monoheteroaryl comprising 3 atoms chosen from nitrogen and sulfur atoms, or completely saturated 6-membered monoheteroaryl comprising 1 heteroatom representing oxygen atom; D4 means compound of the formula: ; D5 means compound of the formula: ; R6 represents (1) hydrogen atom, (2) (C1-C8)-alkyl, (3) -NR7R8 wherein R7 or R8 represent hydrogen atom or (C1-C8)-alkyl, or R7 and R8 taken in common with nitrogen atom to which they are added form saturated 5-6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom representing oxygen atom; E means -CH or nitrogen atom; m means a whole number 1-3, or its nontoxic salt. Invention relates to a regulator activated by peroxisome proliferator receptor, agent used in prophylaxis and/or treatment of diseases associated with metabolism disorders, such as diabetes mellitus, obesity, syndrome X, hypercholesterolemia or hyperlipoproteinemia, hyperlipidemia, atherosclerosis, hypertension, diseases coursing with circulation disorder, overeating or heart ischemic disease, and to an agent that increases cholesterol level associated with HDL, reduces cholesterol level associated with LDL and/or VLDL, eliminates risk factor in development of diabetes mellitus and/or syndrome X and comprising a compound represented by the formula (I) or its nontoxic salt as an active component and a carrier, excipient or solvent optionally. Invention proposes derivative compounds of carboxylic acid possessing the modulating activity with respect to peroxisome proliferator receptor (PPAR).

EFFECT: valuable medicinal properties of compounds.

15 cl, 5 tbl, 48 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new compounds of general formula II , wherein X, Y represent N; Z O; Ar1 represents 2-piridyl; Ar2 represents phenyl and at least one from Ar1 and Ar2 is substituted by at least one residue selected from group comprising of -F, -Cl, -Br, -I, -SR, -CN, -C(O)R, -CH(OR)R', -CH2(OR), -CF3, C1-C10-alkyl and aryl, wherein R of R' are H, -CF3, C1-C10-alkyl and aryl or together form a ring, except for 3-(2-piridyl)-5-(2-chlorophenyl)-1,2,4-oxadiazole or 3-(2-piridyl)-5-[3-(trifluotomethyl)phenyl]-1,2,4-oxadiazole; or to new compounds as defined in specification; as well as pharmaceutical composition having activity in relation to metabothrophic glutamate receptors based on the same and method for modulating of metabothrophic glutamate receptors.

EFFECT: new compounds useful as modulators of metabothrophic glutamate receptors.

14 cl, 10 ex, 1 dwg

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to using phenylethenyl- or phenylethynyl-derivatives as antagonists of glutamates receptors. Invention describes using compound of the general formula (I):

wherein each among R1, R2, R3, R4 and R5 means independently of one another hydrogen atom, (C1-C6)-alkyl, -(CH2)n-halogen, (C1-C6)-alkoxy-group, -(CH2)n-NRR', -(CH2)n-N(R)-C(O)-C1-C6)-alkyl, phenyl or pyrrolyl that can be unsubstituted or substituted with one or more (C1-C6)-alkyl; each among R, R' and R'' means independently of one another hydrogen atom or (C1-C6)-alkyl; A means -CH=CH- or C≡C; B means ,, , , or wherein R6 means hydrogen atom, (C1-C)-alkyl, -(CH2)n-C(O)OR, or halogen atom; R7 means hydrogen atom, (C1-C6)-alkyl, -(CH2)n-C(O)OR', halogen atom, nitro-group or oxodiazolyl group that can be unsubstituted or substituted with (C1-C6)-alkyl or cycloalkyl; R8 means hydrogen atom, (C1-C6)-alkyl, -(CH2)n-OH, -(CH2)n-C(O)OR'' or phenyl; R9 means (C1-C6)-alkyl; R10 and R11 mean hydrogen atom; R12 means -(CH2)n-N(R)-C(O)-(C1-C6)-alkyl; R13 means hydrogen atom; each R14, R15, R16 and R17 independently of one another means hydrogen atom or (C1-C6)-alkoxy-group; each R18, R19 and R20 independently of one another means hydrogen atom; R21 means hydrogen atom or (C1-C6)-alkyl; R22 means hydrogen atom, (C1-C6)-alkyl or (C1-C6)-alkyl comprising one or more substitutes chosen from groups hydroxy- or halogen atom; R23 means hydrogen atom, (C1-C6)-alkanoyl or nitro-group; each among R24, R25 and R26 independently of one another means hydrogen atom or (C1-C6)-alkyl; n = 0, 1, 2, 3, 4, 5 or 6; X means -O- or -S-; Y means -CH= or -N=, and its pharmaceutically acceptable salts used in preparing medicinal agents designates for treatment or prophylaxis of disorders mediated by mGluR5-receptors. Also, invention describes compounds of the formula (I-A), compound of the formula (I-B-1) given in the invention description, and a medicinal agent used in treatment or prophylaxis of disorders mediated by mGluR5-receptors.

EFFECT: valuable medicinal properties of compounds.

44 cl, 1 tbl, 44 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of 4-phenylpyridine of the general formula: (I) wherein R means halogen or halogen atom; R1 means -(C≡C)mR1' or -(CR'=CR'')mR1'; X means -C(O)N(R8)-, -N(R8)C(O)- or -N(R8)-(CH2)p- wherein m = 0-4 and p = 1-2; values of radicals R1', R2, R3', R3, R4, R4', R8, R' and R'' are given above, and to their pharmaceutically acceptable acid-additive salts and a medicinal agent based on thereof. New compounds are neurokinine-1 antagonists and can be used as medicinal agents in treatment of diseases mediated by neurokinine-1 receptors.

EFFECT: valuable medicinal properties of derivatives.

13 cl, 119 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of 4-phenylpyridine of the following general formulae: (IA)

and (IB) wherein R1 means and , or -NH(CH2)2OH, -NR3C(O)CH3 or -NR3C(O)-cyclopropyl; R2 means methyl or chlorine atom; R3 means hydrogen atom or methyl; R means hydrogen atom or -(CH2)2OH; n = 1 or 2, and their pharmaceutically acceptable acid-additive salts. Also, invention describes a medicinal agent possessing effect of agonist of NK-1 receptors based on these compounds. Proposed compounds show good affinity degree to NK-1 receptors and can be used in treatment or prophylaxis of diseases associated with these receptors.

EFFECT: valuable medicinal properties of compounds and agent.

10 cl, 1 tbl, 14 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to mesylates of group of derivatives of piperazine and to a method for preparing indicated mesylates by economy method with high yield and purity. Method for synthesis of piperazine ring and formation of mesylate is carried out by the general stage in interaction of amine of the formula (2): with compound of the formula (3): and methanesulfonic anhydride wherein Y represents methyl, benzyl or meta-phenylbenzyl to yield mesylate compounds of the formula (1):

EFFECT: improved preparing method.

8 cl, 1 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to derivatives of dihydronaphthalene represented by the formula (I):

wherein radical values are determined in the description and to its nontoxic salts. The proposed compound is a regulator of receptors activated by a peroxisome proliferator (PPAR) of α- and γ-type. The agent can be useful as a hypoglycemic agent, hypolipidemic agent, agent for prophylaxis and/or treatment of diseases associated with metabolic disturbances, agent increasing the content of HDL-cholesterol and reducing the content of LDL-cholesterol and/or VLDL-cholesterol and agent for weakening diabetes mellitus factor risk, and/or X-syndrome. Also, invention claims derivative of dihydronaphthalene representing 3-{5-{2-[2-(4-methylphenyl)-5-methyloxazol-4-yl]ethoxy}-3,4-dihydronaphthalen-1-yl}propanoic acid.

EFFECT: valuable medicinal properties of compounds and agent.

21 cl, 15 tbl, 14 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of 4-phenylpyridine N-oxides of the general formula (I) and their pharmaceutically acceptable acid-additive salts wherein R means hydrogen atom, lower alkyl or halogen atom; R1 means hydrogen atom; R2 and R2' mean independently of one another hydrogen, halogen atom, trifluoromethyl group, (lower)-alkoxy-group; or R2 and R2' can mean in common the group -CH=CH-CH=CH- optionally substituted with one or two substitutes taken among lower alkyl or (lower)-alkoxy-group; R3 and R3' mean independently of one another hydrogen atom, lower alkyl; R4 and R4' mean independently of one another -(CH2)mOR6 or lower alkyl; or R4 and R4' form in common with N-atom to which they are bound substituted R5-cyclic tertiary amine representing pyrrolidine-1-yl, piperidine-1-yl, piperazine-1-yl, morpholine-4-yl or 1,1-dioxomorpholine-4-yl; R5 means hydrogen atom, hydroxyl, -COOR3, -N(R3)CO-lower alkyl or -C(O)R3; R6 means hydrogen atom, lower alkyl; X means -C(O)N(R6)-, -N(R6)C(O)-; n = 0, 1, 2, 3 or 4; m = 1, 2 or 3. Also, invention describes a medicinal agent comprising these compounds. Compounds can be used as drugs in treatment or prophylaxis of diseases associated with antagonists of NK-1 receptor.

EFFECT: valuable medicinal properties of agent.

6 cl, 32 ex

FIELD: agriculture, in particular method for controlling of specific insect pests.

SUBSTANCE: invention relates to method for controlling of lepidopterous, homopterous, hemipterans, coleopterous, and physopods by contacting of said pests or environment thereof with effective amount of compound of formula I SSS1, N-oxide or agriculturally acceptable salt thereof being effective against abovementioned insects, wherein A and B are independently O or S; R1, R2 represent H, C1-C6-alkyl; R3 represents H, optionally substituted C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkinyl, or C3-C6-cycloalkyl; R4 represents H, C1-C6-alkyl, C2-C6-alkinyl, C1-C6-haloalkyl, CN, halogen, C1-C4-alkoxy, C1-C4-haloalkoxy, NO2;. R5 represents H, C1-C6-alkyl, C1-C6-haloalkyl, C1-C4-hydroxyalkyl, CO2R11R12, halogen or C1-C4-alkoxy; R6 represents H, C1-C6-alkyl, C1-C6-haloalkyl; R7 represents H, C1-C6-alkyl, C2-C6-alkenyl, C1-C6-haloalkyl, phenyl ring, benzyl ring, or 5-6-membered heteroaromatic rind, naphthyl ring system, or 8-10-membered condensed heterodicyclic system. Also claimed are compound of formula I and benzoxazine derivative of formula 10 .

EFFECT: compounds effective against agriculture spineless depredators.

22 cl, 13 tbl, 1 dwg, 24 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of azole of the formula:

wherein R1 represents (1) halogen atom; (2) nitrogen-containing 5- or 6-membered heterocyclic group comprising from 1 to 4 nitrogen atoms as atoms of ring system in addition to carbon atoms, and group with condensed rings comprising nitrogen-containing 5- or 6-membered heterocyclic group comprising 1-2 nitrogen atoms as atoms of ring system in addition to carbon atoms, and benzene ring wherein nitrogen-containing 5- or 6-membered heterocyclic group and group with condensed rings can comprise optionally from 1 to 3 substituted taken among group consisting of: (i) aliphatic hydrocarbon group comprising from 1 to 15 carbon atoms; (ii) (C6-C14)-aryl group, and (iii) carboxy-group that can be in form of group of (C1-C6)-alkyl ester wherein above indicated substitutes (i)-(iii) can have from 1 to 3 substituted additionally taken among group consisting of: (a) carboxyl group and (b) hydroxy-group; (3) (C1-C10)-alkylsulfanyl group that can be substituted with hydroxy-group; (4) heteroarylsulfanyl group taken among pyridylsulfanyl, imidazolylsulfanyl and pyrimidinylsulfanyl, or (5) amino-group that can be mono- or di-substituted optionally with substitutes(substitutes) among group consisting of: (i) (C1-C10)-alkyl group that can be substituted with hydroxy-group, and (ii) (C7-C10)-aralkyl group; Ab represents aryloxy-group that is substituted with alkyl group and can be substituted with halogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkyl group, hydroxy-group or (C1-C6)-alkylcarbonyloxy-group additionally; B represents (C6-C14)-aryl group or thienyl group each of that can has optionally from 1 to 4 substitutes taken among halogen atom, (C1-C6)-alkoxy-group and (C1-C6)-alkyl group that can has optionally from 1 to 3 halogen atoms; Y represents saturated aliphatic bivalent group with direct or branched chain and having from 1 to 7 carbon atoms, or to its salt. Also, invention relates to a pharmaceutical composition that elicits activity for promoting production/secretion of neurotrophine, and to methods for prophylaxis and treatment based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof used for prophylaxis and treatment of neuropathy.

EFFECT: improved and valuable medicinal properties of agent, improved methods for treatment.

19 cl, 1 dwg, 5 tbl, 122 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of quinoline of the formula (I): wherein R1 and R2 are chosen independently from hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, alkylcarbonyl, cycloalkylcarbonyl, phenyl, unsubstituted benzyl or benzyl substituted with halogen atom, cyano-group, trifluoromethyl, alkyl, alkoxy-group, benzylcarbonyl, pyridinyl, furyl, thiophenyl, indanyl, phenyl-SO2-, pyridinyl-SO2-, thiophenyl-SO2; or R1 and R2 in common with atom N to which they are added form piperidino-group, pyrrolidinyl, morpholinyl, azepanyl, 3,4-dihydro-1H-isoquinolinyl, and wherein heterocyclic ring is optionally substituted with one or some substitutes chosen independently from alkyl and alkoxy-group; R3 represents hydrogen atom, alkyl; R4 represents hydrogen atom; A in common with nitrogen atom that is added to quinoline ring represents pyrrolidinyl, azepanyl, and ring A is optionally substituted with one-three substitutes chosen independently from alkoxy-group, hydroxyalkyl, alkoxyalkyl. Also, invention describes methods of synthesis of quinoline derivatives of the formula (I). Proposed compounds can be used as components of pharmaceutical formulations in treatment or prophylaxis of arthritis, cardiovascular diseases, diabetes mellitus, renal insufficiency, disorders in food eating and obesity.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

20 cl, 122 ex

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