5-fluoropyrimidine derivatives as fungicides

FIELD: chemistry.

SUBSTANCE: invention relates to novel fungicidally active 5-fluoropyrimidines of general formula I. In compounds of formula , R1 is -N(R3)R4; R2 is -OR21; R3 is: H; C1-C6-alkyl, optionally substituted with 1-3 groups R5; C2-C6-alkenyl, optionally substituted with 1-3 groups R5; a 5- or 6-member heteroaromatic cycle, selected from a group consisting of furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl; wherein each heteroaromatic cycle is optionally substituted with 1-3 R29 groups; 3H-isobenzofuran-1-oyl; -C(=O)R6; -C(=S)R6; -C(=S)NHR8; -(=O)N(R8)R10; -OR7; -P(O)(OR15)2; -S(O)2R8;-SR8; -Si(R8)3; -N(R9)R10; -(CHR24)mOR29 or -C(=NR16)SR16; where m equals an integer from 1 to 3; R4 is: H; C1-C6-alkyl, optionally substituted with 1-3 R5 groups; or -C(=O)R6; alternatively, R3 and R4 together can form: a 5- or 6-member saturated or unsaturated cycle containing 1-2 heteroatoms selected from N and O, where each cycle can be optionally substituted with 1-3 R11 groups; =C(R12)N(R13)R14 or =C(R15)OR15. The rest of the radicals are given in the claim.

EFFECT: obtaining novel fungicidally active 5-fluoropyrimidines of general formula I.

4 cl, 3 tbl, 1 ex

 

Cross-reference to related applications

In this application claims the benefit of priority of provisional patent application U.S. serial No. 61/011799, filed January 22, 2008, and provisional patent application U.S. serial No. 61/115297, filed November 17, 2008

The technical field to which the invention relates

The present invention relates to the field of 5-torpedinidae and their derivatives and to the use of these compounds as fungicides.

The prior art and the invention is

Fungicides are compounds of natural or synthetic origin, which are used for plant care and plant protection against damage caused by the relevant agricultural fungi. Usually one fungicide may not be applicable in all situations. Therefore, the study continues with the aim of obtaining fungicides that may have better efficiency, more convenient to use and are cheaper.

The present invention relates to 5-ftorpirimidinov compounds and their use as fungicides. Compounds according to the present invention can provide protection against records of Ascomycetes, basidiomycetes, deuteromycetes and oomycetes.

One of the embodiments of the present invention can switch the diamonds in the compounds of formula I

where R1represents-N(R3R4;

R2represents-OR21;

R3represents:

H;

C1-C6-alkyl, optionally substituted by 1 to 3 groups of R5;

C2-C6alkenyl, optionally substituted by 1 to 3 groups of R5;

5 - or 6-membered heteroaromatic cycle selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl, with each heteroaromatic cycle optionally substituted by 1 to 3 groups of R30;

the imidazole fused with an aromatic or heteroaromatic cycle selected from the group consisting of benzene, oxazole, isoxazol, furan, thiazole, pyrimidine, pyridine, pyrrole, pyrazine, thiophene, with each an aromatic or heteroaromatic cycle optionally substituted by 1 to 3 groups of R30;

benzo[1,3]dioxole;

3H-isobenzofuran-1-IMT;

cyano;

C3-C6-quinil, optionally substituted by 1 to 3 groups of R5;

-C(=O)R6;

-C(=O)OCH2C(=O)R8;

-C(=S)R6;

-C(=S)other8;

-C(=O)N(R8R10;

-OR7;

-P(O)(OR15)2;

-S(O)2R8;

-SR8;

-Si(R8)3

-N(R9R10;

-N=C(R15R16;

-(CHR22)mR37;

-(CHR24OR29or

-C(=NR16)SR16;

where m is an integer from 1 to 3;

R4represents:

H;

C1-C6-alkyl, optionally substituted by 1 to 3 groups of R5;

-C(=O)R6or

-C(=O)N(R8R10;

alternatively, R3and R4taken together can form:

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;

=C(R12)N(R13R14;

=C(R13)(R14);

=C(R15OR15;

=S(R34)2or

=NR35;

R5independently represents halogen, C1-C6-alkyl, C1-C4-halogenated, C1-C4-alkoxy, C1-C4-halogenoalkane, C1-C4-alkylthio, C1-C4-allogenicity, amino, C1-C3-alkylamino, C2-C6-alkoxycarbonyl, C2-C6-alkylsulphonyl, C2-C6-alkylaminocarbonyl, -OH, N-methylpiperazine or C3-C6-trialkylsilyl;

R6independently represents H, C1-C6-alkyl, C1-C5-halogenated, C1-C5-alkoxy, C1-C5-halogenoalkane, C2-C6 -alkoxycarbonyl, C1-C4-alkoxyalkane, C2-C6-alkylaminocarbonyl; 1-benzo[1,2,3]thiadiazole-7-yl, thiazolyl, benzyl, phenyl, phenoxy or benzyloxy, where thiazolyl, benzyl, phenyl, phenoxy or benzyloxy optionally can be substituted by 1 to 3 groups of R20A 5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;

R7represents H, C1-C6-alkyl, C2-C6alkenyl, C1-C5-halogenated, benzyl which optionally may be substituted by 1-5 groups R20, CHR18C(O)OR19or 5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;

R8independently represents a C1-C6-alkyl, C1-C6-halogenated, amino, C1-C6-alkylamino, C2-C6-dialkylamino, phenyl, optionally substituted by 1 to 3 groups of R30or 5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;

R9represents H, C1-C6-alkyl, C1-C6-halogenated, -C(=O)R17or phenyl, optionally substituted by 1 to 3 groups of R20;

R10represents H or C1-C6-alkyl, C1-C6-halogenated or phenyl, optionally substituted by 1 to 3 groups of R20;

R11independently represents halogen, C1-C6-alkyl, C1-C6-halogenated, C1-C6-alkoxy, C1-C6-halogenoalkane, C1-C6-alkylthio, C1-C6-allogenicity, amino, C1-C6-alkylamino, C2-C6-dialkylamino, C2-C6-alkoxycarbonyl or C2-C6-alkylsulphonyl;

R12represents H or C1-C4-alkyl;

R13and R14independently represent H, cyano, -OH, C1-C4-alkyl, C1-C6-alkoxy, C2-C6-alkylsulphonyl, phenyl or benzyl, where phenyl or benzyl optionally may be substituted by 1 to 3 groups of R20;

alternatively, R13and R14taken together can form:

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11or 3,4-dihydro-1H-isoquinoline-2-yl;

alternatively, R12and R13taken together can form:

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1-3 is the group R 11;

R15represents H or C1-C6-alkyl;

R16represents H, C1-C6-alkyl or phenyl, optionally substituted by 1 to 3 groups of R20;

alternatively, R15and R16can be taken together to form -(CH2)4- or -(CH2)5-;

R17represents H, C1-C6-alkyl, C1-C6-halogenated, C1-C6-alkoxy, phenyl, phenoxy or benzyloxy, where each cycle may not necessarily be substituted by 1 to 3 groups of R20;

R18represents H, C1-C6-alkyl or C1-C6-halogenated;

R19represents H, C1-C6-alkyl, C1-C6-halogenated or benzyl;

R20independently represents halogen, cyano, nitro, amino, C1-C6-alkoxyalkane, C1-C6-alkyl, C1-C6-halogenated, C1-C6-hydroxyalkyl, C2-C6-alkoxyalkyl, C2-C6-halogenoacetyl, C2-C6alkenyl, C2-C6-halogenoalkanes, C3-C6-quinil, C3-C6-halogenoalkanes, hydroxyl, C1-C6-alkoxy, C1-C6-halogenoalkane, C2-C6-alkenylamine, C2-C6-halogenations, C3-C6-alkyloxy, C3-C6-halogenoalkanes the XI, C1-C6-alkylthio, C1-C6-allogenicity, C1-C6-alkylsulfonyl, C1-C6-halogenallylacetic, C2-C6-alkanity, C2-C6-halogenalkane, C2-C6-halogenallylacetic, C3-C6-alkylthio, C3-C6-alkylsulfonyl, C3-C6-halogenallylacetic, C1-C6-alkylamino, C2-C8-dialkylamino, C3-C8-dialkylaminoalkyl, C2-C6-alkoxycarbonyl, C2-C6-alkylsulphonyl, C3-C6-trialkylsilyl, 2-[(E)-methoxyimino]-N-methylacetamide, phenyl, benzyl, benzyloxy, phenoxy or 5 - or 6-membered heteroaromatic cycle, where each phenyl, benzyl, benzyloxy, phenoxy or 5 - or 6-membered heteroaromatic cycle optionally may be substituted by 1-3 substituents, independently selected from the group R31;

R21represents:

H;

C1-C14-alkyl;

C1-C6-halogenated;

C2-C4alkenyl;

C2-C4-halogenoalkanes;

C3-C4-quinil;

C3-C4-halogenoalkanes;

phenyl, naphthyl or tetrahydropyranyl, each of which is optionally substituted by 1 to 3 groups of R20;

-(CHR22)mR23;

-(CHR24)mC(O)OR25;

-(CHR24)mC(O)R26

-(CHR24)mC(O)N(R27R28;

-(CHR24)mOR29;

-(CHR24)mSR29

-(CHR24)mN(R27R28;

-C(=O)R32;

-N=C(R32)(R36);

-NR25C(=O)OR25;

-Si(R8)3;

-SO2R33;

C2-C6-alkoxycarbonyl;

C2-C6-alkylaminocarbonyl;

C2-C6-alkylsulphonyl;

sugar selected from the group consisting of beta-D-gluconacetobacter, ramnose, fructose and pentoses; or

5 - or 6-membered heteroaromatic cycle selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, triazolyl or isoxazolyl, where each 5 - or 6-membered heteroaromatic cycle optionally may be substituted by 1-5 groups R20;

R22independently represents:

H;

halogen;

cyano;

nitro;

C1-C6-alkyl;

C1-C6-halogenated;

phenyl or benzyl, optionally substituted by 1 to 3 groups of R20;

C1-C6-hydroxyalkyl;

C2-C6-alkoxyalkyl;

C3-C6-halogenoalkanes;

C2-C6alkenyl;

C2-C6-halogenoalkanes;

C3-C6-quinil;

C1-C6-is laksi;

C1-C6-halogenoalkane;

C1-C6-alkylthio;

C1-C6-alkylamino;

C2-C8-dialkylamino;

C3-C6-cyclooctylamino;

C4-C6-(alkyl)cyclooctylamino;

C2-C6-alkylsulphonyl;

C2-C6-alkoxycarbonyl;

C2-C6-alkylaminocarbonyl;

C3-C8-dialkylaminoalkyl;

C3-C6-trialkylsilyl;

heteroaromatic cycles with condensed rings selected from the group consisting of benzothiophene, chinoline, izochinolina, thieno[2,3-b]pyridyl, 1-methyl-1H-thieno[2,3-c]pyrazolyl and benzoimidazolyl, where each cycle may be optionally substituted by 1 to 3 groups of R20; or

5 - or 6-membered heteroaromatic cycle selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl and tanila;

R23represents:

H;

halogen;

C1-C6-alkyl;

C1-C6-halogenated;

C2-C6-dialkylamino;

phenyl, optionally substituted by 1-5 groups R20;

heteroaromatic cycles with condensed rings selected from the group consisting of benzothiophene, chinoline, ethenolysis is, thieno[2,3-b]pyridyl, 1-methyl-1H-thieno[2,3-c]pyrazolyl, benzofuranyl and benzoimidazolyl, 2,3-dihydrobenzofuran-2-yl, 4-methyl-4H-thieno[3,2-b]pyrrol-5-yl, 1-methyl-1H-indol-5-yl, imidazo[1,2-a]pyridine-2-yl, imidazo[2,1-b]thiazol-6-yl, benzothiazol-2-yl, benzo[b]thiophene-7-yl and 1-methyl-1H-indazol-3-yl, where each cycle may be optionally substituted by 1 to 3 groups of R20;

naphthyl;

benzo[1,3]dioxole;

pyrrolidinone;

oxetanyl;

C1-C6-alkylthio, optionally substituted by 1-5 groups R20;

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11; or

5 - or 6-membered heteroaromatic cycle selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl, imidazolyl, thiophene-2-yl and thiophene-3-yl, where each heteroaromatic cycle optionally may be substituted by 1 to 3 groups of R20;

R24represents H, C1-C6-alkyl, C1-C6-alkoxy, benzyl or phenyl, where each of the benzyl or phenyl optionally may be substituted by 1 to 3 groups of R20;

R25represents H, C1-C6-alkyl, phenyl or benzyl, long is Ino substituted by 1 to 3 groups of R 20;

R26represents:

H;

C1-C6-alkyl;

C1-C6-alkoxy;

phenyl, optionally substituted by 1 to 3 groups of R20; or

5 - or 6-membered heteroaromatic cycle selected from the group consisting of furanyl, pyridinyl, pyridinyl-N-oxide, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, triazinyl, thiadiazolyl, oxazolyl, triazolyl and isoxazolyl;

R27and R28independently represent:

H;

C1-C6-alkyl;

benzyl or phenyl, where each of the benzyl or phenyl optionally may be substituted by 1 to 3 groups of R20; or

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;

R29represents:

H;

C1-C6-alkyl;

C1-C6-halogenated;

C1-C6-alkoxyalkyl;

C2-C6-alkylsulphonyl;

benzyl or phenyl, where each of the benzyl or phenyl optionally may be substituted by 1 to 3 groups of R20; or

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;

R30independently represents halogen, cyano, nitro, C1-C6-alkyl, C1-C6Gal is penalcol, C1-C6-hydroxyalkyl, C2-C6-alkoxyalkyl, C2-C6-halogenoacetyl, C2-C6alkenyl, C2-C6-halogenoalkanes, C3-C6-quinil, C3-C6-halogenoalkanes, hydroxyl, C1-C6-alkoxy, C1-C6-halogenoalkane, C2-C6-alkenylamine, C2-C6-halogenations, C3-C6-alkyloxy, C3-C6-halogenaryloxy, C1-C6-alkylthio, C1-C6-alkylsulfonyl, C1-C6-halogenallylacetic, C2-C6-alkanity, C2-C6-halogenalkane, C2-C6-halogenallylacetic, C3-C6-alkylthio, C3-C6-alkylsulfonyl, C3-C6-halogenallylacetic, C1-C6-alkylamino, C2-C8-dialkylamino, C3-C8-dialkylaminoalkyl, C3-C6-trialkylsilyl, thiazolyl, phenyl, pyrimidinyl or pyridyl, where thiazolyl, phenyl, pyridyl or pyrimidinyl optionally can be substituted by 1 to 3 groups of R20;

R31independently represents halogen, cyano, nitro, C1-C6-alkyl, C1-C6-halogenated, C1-C6-hydroxyalkyl, C2-C6-alkoxyalkyl, C2-C6-halogenoacetyl, C2-C6alkenyl, C2-C6-halogen is canil, C3-C6-quinil, C3-C6-halogenoalkanes, hydroxyl, C1-C6-alkoxy, C1-C6-halogenoalkane, C2-C6-alkenylamine, C2-C6-halogenations, C3-C6-alkyloxy, C3-C6-halogenaryloxy, C1-C6-alkylthio, C1-C6-alkylsulfonyl, C1-C6-halogenallylacetic, C2-C6-alkanity, C2-C6-halogenalkane, C2-C6-halogenallylacetic, C3-C6-alkylthio, C3-C6-alkylsulfonyl, C3-C6-halogenallylacetic, C1-C6-alkylamino, C2-C8-dialkylamino, C3-C8-dialkylaminoalkyl or C3-C6-trialkylsilyl;

R32independently represents:

C1-C6-alkyl, C1-C6-halogenated, C1-C6-hydroxyalkyl, C2-C6-alkoxyalkyl, C2-C6-halogenoacetyl, C2-C6alkenyl, C2-C6-halogenoalkanes, C3-C6-quinil, C3-C6-halogenoalkanes, hydroxyl, C1-C6-alkoxy, C1-C6-halogenoalkane, C2-C6-alkenylamine, C2-C6-halogenations, C3-C6-alkyloxy, C3-C6-halogenaryloxy, C1-C6-alkylthio, C1-C6alkylsulfonyl, C1-C6-halogenallylacetic, C2-C6-alkanity, C2-C6-halogenalkane, C2-C6-halogenallylacetic, C3-C6-alkylthio, C3-C6-alkylsulfonyl, C3-C6-halogenallylacetic, C1-C6-alkylamino, C2-C8-dialkylamino, C3-C8-dialkylaminoalkyl, C3-C6-trialkylsilyl;

phenyl, where the phenyl cycle optionally may be substituted by 1 to 3 groups of R20; or

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;

R33independently represents:

C1-C6-alkyl, C1-C6-halogenated, phenyl or thienyl, optionally substituted by 1 to 3 groups of R20; or

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;

R34represents:

C1-C6-alkyl, C1-C6-halogenated, C2-C6-alkoxyalkyl, C1-C6-alkylamino or

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;

R35represents:

C 1-C6-alkyl, C2-C6-alkylsulphonyl or

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;

R36represents H, cyano, C1-C6-alkyl, C1-C6-alkoxy, benzyl or phenyl, where each of the benzyl or phenyl optionally may be substituted by 1 to 3 groups of R20;

alternatively, R32and R36taken together can form:

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11; and

R37independently represents:

H, halogen or phenyl, optionally substituted by 1-5 groups R20;

C1-C6-alkyl, C1-C6-halogenated, hydroxyl, C1-C6-alkoxy or C1-C6-halogenoalkane or

5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11.

Another variant implementation of the present invention may include fungicidal composition for combating fungi or prevent fungi, containing the following compounds and botanically acceptable substance carrier.

Even Odie is a variant of implementation of the present invention may include a method of combating fungi or prevent damage to plants, fungi, the method includes the stage of applying fungicide effective amount of one or more of the following compounds, at least one of fungi, one of the plants, the area adjacent to the plant, and the seeds that are adapted to the reproduction of plants.

The term "alkyl" refers to an unbranched, branched or cyclic chain of carbon atoms, including methyl, ethyl, propyl, butyl, isopropyl, isobutyl,tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

The term "alkenyl" refers to a branched, unbranched or cyclic chain of carbon atoms containing one or more double bonds, including ethynyl, propenyl, butenyl, Isopropenyl, Isobutanol, cyclohexanol etc.

The term "quinil" refers to a branched or unbranched chain of carbon atoms containing one or more triple relations, including PROPYNYL, butynyl etc.

Used in this description, the term 'R' refers to the group consisting of C2-8-alkyl, C3-8-alkenyl or C3-8-quinil, unless otherwise specified.

The term "alkoxy" refers to the Deputy-OR.

The term "alkoxycarbonyl" refers to the Deputy-C(O)-OR.

The term "alkylaryl" refers to the Deputy-C(O)-R.

The term "alkylsulfonyl" refers to the Deputy-SO2-R.

the Ermin "halogenallylacetic" refers to sulfonylurea substitution on the alkyl, which is partially substituted by halogen atoms.

The term "alkylthio" refers to the Deputy-S-R.

The term "alkylaminocarbonyl" refers to the Deputy-C(O)-N(H)-R.

The term "dialkylaminoalkyl" refers to the Deputy-C(O)-NR2.

The term "alkylcyclohexane" refers to cyclooctylamino-Deputy, which is substituted by an alkyl group.

The term "trialkylsilyl" refers to-SiR3.

The term "cyano" refers to the Deputy-C≡N.

The term "hydroxyl" refers to the Deputy-OH.

The term "amino" refers to the Deputy-NH2.

The term "alkylamino" refers to the Deputy-N(H)-R.

The term "dialkylamino" refers to the Deputy-NR2.

The term "alkoxyalkyl" refers to-O(CH2)nO(CH2)nwhere n is an integer from 1 to 3.

The term "alkoxyalkyl" refers to alkoxy-substitution on the alkyl.

The term "halogenoacetyl" refers to alkoxy-substitution on the alkyl which may be partially substituted by halogen atoms.

The term "hydroxyalkyl" refers to alkyl, which is substituted by a hydroxyl group.

The term "halogenoalkane" refers to the Deputy-OR-X, where X represents Cl, F, Br or I, or any combination thereof.

The term "halogenated" refers to alkyl, which is substituted by Cl, F, I or Br or any combination thereof.

The term "halogenoalkanes" relative who are getting ready for alkenyl, which is substituted by Cl, F, I or Br or any combination thereof.

The term "halogenoalkanes" refers to the quinil, which is substituted by Cl, F, I or Br or any combination thereof.

The term "halogen" or "halo" refers to one or more halogen atoms, defined as F, Cl, Br and I.

The term "hydroxycarbonyl" refers to the Deputy-C(O)-OH.

The term "nitro" refers to the Deputy-NO2.

The term "thienyl" refers to 5-membered aromatic cycle with one atom of sulfur.

Throughout the description of the invention refers to compounds of formula I also includes optical isomers, and salts of formula I and their hydrates. In particular, when formula I is an alkyl group branched chain, it is clear that such connections include optical isomers and racemates. Typical salts include hydrochloride, hydrobromide, hydroiodide, etc.

Professionals in this field also understand that unless otherwise specified, the allowable additional substitution, provided that it satisfies the rules of chemical bonding and strain energy, and the product still possesses fungicidal activity.

Another variant implementation of the present invention relates to the use of compounds of formula I to protect plants from damage caused by phytopathogenic microorganism, or to processing plants infected with F. copathogens the microorganism, includes the application of the compounds of formula I or compositions containing compound, on soil, plant, plant part leaves and/or seeds.

Additionally, another variant implementation of the present invention relates to compositions suitable for protecting plants from damage by phytopathogenic microorganism and/or processing plants infected by phytopathogenic microorganism containing the compound of the formula I and botanically acceptable substance carrier.

Detailed description of the present invention

Compounds according to the present invention can be applied to any of several known methods or in the form of compounds or compositions containing compounds. For example, the compounds can be applied to the roots, seeds or leaves of plants to fight against various fungi without prejudice to the market value of the plants. Substances can be applied in the form of any of the commonly used types of formulations, such as solutions, dusters, able to absorb moisture powders, flowable concentrates or concentrates of emulsions.

Compounds according to the present invention is preferably applied in the form of a composition containing one or more compounds of the formula I with botanically acceptable carrier. Concentrated compositions for application can be atomized in water or friend who's fluids, or composition can be a powder or granular formulations, which can be applied without additional processing. The compounds can be obtained according to procedures that are generally accepted in the field of agricultural chemical products.

In the present invention assumes the use of all media through which one or more compounds can be in the form of a composition for delivery and use as a fungicide. Typically, the composition is applied in the form of aqueous suspensions or emulsions. Such suspensions or emulsions can be obtained from water-soluble compounds, suspendiruemye in water compositions or emulsifiable compositions which are solids, commonly known as powders that absorb moisture, or liquid, usually known as concentrates, emulsions, aqueous slurry or concentrated suspensions. As it is easy to understand, you can use any substance to which you can add data connection, provided that it provides the required applicability (utility) without significant effect on the activity of such compounds as antifungal agents.

Able to absorb moisture powders that can be pressurized with the formation of dispersible in water granules contain a homogeneous mixture of one or more connected the th formula I, an inert carrier and a surfactant. The concentration of the compound in is able to absorb moisture powder can range from about 10 mass. percent to about 90 wt. percent calculated on the total mass can absorb the moisture of the powder, more preferably from about 25 wt. percent to about 75 mass. percent. When getting able to absorb moisture powder compositions of the compounds can be combined with any fine particulate matter, such as profilic, talc, chalk, gypsum, mullerova earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clay, diatomaceous earth, purified silicates or the like, When such operations micronized carrier and surface-active substances are usually mixed with compound (compounds) and grind.

Concentrates of emulsions of the compounds of formula I may contain a suitable concentration, such as from about 10 mass. percent to about 50 mass. percent of the compounds in a suitable fluid calculated on the total weight of the concentrate. The compounds can be dissolved in an inert carrier, which is either a solvent miscible with water, or a mixture of water-immiscible organic solvents and emulsifiers. The concentrates can be diluted in water and oil with the formation of mixtures for spraying in the form of emulsions of oil-in-water". Applicable organic solvents include aromatic hydrocarbons, in particular high-boiling naphthalene and olefinic fractions of oil, such as heavy naphtha, enriched in aromatic compounds. It is also possible to use other organic solvents such as terpene solvents, including derivatives of rosin, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.

Emulsifiers that can here, it is preferable to use, can be easily specified by experts in this field and include various nonionic, anionic, cationogenic and amphoteric emulsifiers or a mixture of two or more emulsifiers. Examples of nonionic emulsifiers useful for obtaining concentrates of emulsions include ethers of polyalkylene glycols, and condensation products of alkyl - and kilfenora, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propyleneoxide, such as ethoxylated ALKYLPHENOLS and karboksilirovanie esters, solubilisation a polyol or polyoxyalkylene. Cationogenic emulsifiers include Quaternary ammonium compounds and salts of fatty amines of the series. Anionic emulsifiers include oil-soluble salts (e.g. calcium) alkylarylsulfonate the o acids, oil-soluble salts or simple sulfated esters of polyglycol and the corresponding simple salt of phosphated ester of polyglycol.

Typical organic liquids that can be used to obtain concentrates of emulsions of the compounds according to the present invention are aromatic liquids such as xylene, propylbenzene faction; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctylphthalate; kerosene; dialkylamide various fatty acids, in particular dimethylamide glycols, fatty series and derivatives of glycols, such as a simplenbutyl ether, simple ethyl ester or a simple methyl ether of diethylene glycol and simple methyl ester etilenglikola etc. a Mixture of two or more organic liquids can also be used to obtain the emulsion concentrate. Organic liquids include xylene and propylbenzene faction with xylene, the most preferable in some cases. Surface-active dispersing tools are typically used in liquid compositions in amounts of from 0.1 to 20 mass. percent calculated on the total weight of the dispersing means and one or more connections. The compositions can also contain other compatible additives, such as re is ulatory plant growth and other biologically active compounds, used in agriculture.

Aqueous suspensions contain suspensions of one or more water-insoluble compounds of formula I dispersed in the aqueous carrier at a concentration in the range from approximately 5 to approximately 50 mass. percent, based on the total weight of the aqueous suspension. The suspension obtained by fine grinding of one or more compounds and energetic mixing powdered substances and surface-active substances selected from the same types discussed above, with a carrier containing water. To increase the density and viscosity of aqueous media, you can add other components such as inorganic salts and synthetic or natural gums.

The compounds of formula I can also be used in granular compositions, which, in particular, applicable for application to the soil. Granular formulations normally contain from about 0.5 to about 10 wt. percent, based on the total weight of the granular composition, the compounds (compounds), dispersed in an inert carrier, which is entirely or mostly composed of coarse inert substances, such as attapulgite, bentonite, diatomaceous earth, clay or the like cheap material. Such compounds are usually obtained by dissolving the compounds in a suitable solvent and applied on granular media, which is pre-formed to an appropriate particle size in the range from approximately 0.5 to approximately 3 mm, a Suitable solvent is a solvent in which the compound substantially or completely soluble. Such compositions can also be obtained by producing a dense mass or paste of the carrier and compound and solvent and grinding and drying to obtain the desired granular particle.

Dusters, containing the compounds of formula I, can be obtained by thoroughly mixing one or more compounds in powdered form with a suitable powdered agricultural carrier, such as kaolin clay, ground volcanic rock, etc. Dusters can contain from about 1 to about 10 mass. percent of compounds based on the total weight of afiliates.

The compositions can additionally contain auxiliary surfactants to enhance deposition, wetting and penetration of the compounds into the target crop and the microorganism. Such auxiliary surfactants optional can be used as a component of the composition or in the form of a mixture from the tank. The number of auxiliary surfactants usually will Maniatis is from 0.01 to 1.0 volume percent based on the amount of water sprayed, preferably from 0.05 to 0.5 volume percent. Suitable auxiliary surfactants include, but are not limited to, ethoxylated nonylphenols, ethoxylated synthetic or natural alcohols, salts, esters or sulfonating acids, ethoxylated organosilicone, ethoxylated fatty amines of the number and mixture of surface-active substances with mineral or vegetable oils. The compositions can also include emulsion oil-in-water", such as emulsion, described in patent application U.S. serial No. 11/495228, the description of which is expressly incorporated herein by reference.

The compositions optionally may include combinations that contain other pesticide compounds. Such additional pesticidal compounds may include fungicides, insecticides, herbicides, nematicides, miticide, arthropodicides, bactericides or combinations thereof that are compatible with the compounds according to the present invention in the medium selected for application, and help counteract the activity of these compounds. Accordingly, in such embodiments of the invention other pesticide compound used as an additional toxicant for the same or for another application of the pesticide. With the organisations of the formula I and pesticide compound can usually be present in combination in a weight ratio of from 1:100 to 100:1.

Compounds according to the present invention can also be combined with other fungicides with the formation of the fungicidal mixtures and their synergistic mixtures. Fungicidal compounds according to the present invention is frequently applied together with one or more other fungicides to control a broader spectrum of unwanted diseases. When the compounds are used together with the other fungicide (fungicides), we state here the connection can be obtained in the form of a composition with another fungicide (fungicides), mix in the tank with the other fungicide (fungicides) or applied sequentially with the other fungicide (fungicides). Other fungicides such may include 2-(thiocyanatomethylthio)benzothiazole, 2-phenylphenol, sulfate, 8-hydroxyquinoline solution, antimycin, ampelomyces, quisqualis, azaconazole, AZOXYSTROBIN, bacteriaBacillus subtilisbenalaxyl, benomyl, benthiavalicarb-isopropyl, benzylaminocarbonyl salt (BABS), bicarbonate, biphenyl, bicortical, bitertanol, blasticidin-S, borax, Bordeaux mixture (Bordeaux mixture), boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, Captan, carbendazim, carboxin, cropropamide, carvon, chloroneb, CHLOROTHALONIL, chlozolinate, strain Coniothyrium minitans, copper hydroxide, octanoate copper, copper oxychloride, copper sulphate, copper sulphate (rejonowy), copper oxide (I), cyazofamid cyflufenamid, of having cymoxanil, tsyprokonazolu, cyprodinil, dazomet, dibakar, ethylenebis(dithiocarbamate) diammonium, dichlofluanid, dichlorophen, diclocil, declomycin, dichloran, dietphenterm, difenoconazol, difenzoquat-ion, diplomatarium, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap, diphenylamine, dithianon, dodemont, dodemont-acetate, dodine, dodine in free base form, edifenphos, anestrous, epoxiconazol, ethaboxam, ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fanforum, fenhexamid, phenoxyl, fenpiclonil, fenpropidin, fenpropimorph, fentin, fentin acetate, fentin hydroxide, ferbam, verison, fluazinam, fludyoksonil floorf, fluopicolide, perimed, fluoxastrobin, fluquinconazole, flusilazole, glucolipid, flutolanil, flutriafol, folpet, formaldehyde, fosetyl, fosetyl-aluminum, fuberidazole, parallaxis, parameter, guazatine, guazatine acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalil sulfate, kabekona, iminoctadine, iminoctadine-triacetate, iminoctadine-Tris(albuteral), ipconazole, iprobenfos, iprodion, iprovalicarb, isoprothiolane, kasugamycin, hydrate hydrochloride kasugamycin kresoxim-methyl, marcopper, MANCOZEB, mandipropamid, MANEB, mepanipyrim, mepronil, mercury chloride, mercury oxide, mercury chloride (I), metalaxyl, mefenoxam, IU alexel-M, methamphetamine, methamphetamine-ammonium, METAM-potassium, METAM-sodium, metconazole, metasurfaces, methyliodide, methylisothiocyanate, metiram, metamyosyn, metrafenone, millionizer, myclobutanil, nabam, nitrates-isopropyl, nuarimol, Actelion, furac, oleic acid (fatty acids), orysastrobin, oxadixyl, oxin-copper, expoconsult fumarate, oxycarboxin, peyratout, penconazole, pencycuron, pentachlorophenol laurate of pentachlorphenol, pentopia, acetate finalstate, phosphonic acid, phtalic, picoxystrobin, polyoxin B, polyoxin, palikari, potassium bicarbonate, sulfate calikinakkawhooliena, provensal, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazol, propineb, proquinazid, prothioconazole, pyraclostrobin, pyrazophos, perimutter, pirivenas, Pyrimethanil, pyroquilon, quinoclamine, quinoxyfen, quintozene extractReynoutria sachalinensis, silthiofam, simionato, 2-phenylphenoxide of sodium, bicarbonate of sodium, pentachlorophenoxide sodium, spiroxamine, sulfur, SYP-Z071, SYP-048, tar oils, tebuconazole, tecnazene, tetraconazole, thiabendazol, leflunomid, thiophanate-methyl, thiram, tadini, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, Trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, vinclozolin, zineb, Zir, zoxamide, the strain of fungiCandida oleophilastrain mushrooms Fusariumoxysporum,Gliocladium spp.,Phlebiopsis giganteanthe strain ofStreptomyces griseoviridis,Trichoderma spp., (RS)-N-(3,5-dichlorophenyl)-2-(methoxymethyl)succinimide, 1,2-dichloropropane, hydrate 1,3-dichloro-1,1,3,3-Tetrafluoroethane, 1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane, 2-(2-heptadecyl-2-imidazolin-1-yl)ethanol, 2,3-dihydro-5-phenyl-1,4-dithiin - 1,1,4,4-tetroxide, acetate 2-methoxyacetate, chloride 2-methoxyacetate, silicate 2-methoxyacetate, 3-(4-chlorophenyl)-5-methyladenine, 4-(2-nitroprop-1-enyl)poilticians: Aspropyrgos, anilazine, azithrom, barium polysulfide, Bayer 32394, Benadryl, banklinks, Pantaloon, benzamycin; benzamycin-isobutyl, betamorph, binapacryl, sulfate bis(methyl)oxide bis(anti), butiaba, chromate/sulfate cadmium-calcium-copper-zinc, Carnamah, CECA, clobetasol, chloronitromethane, chlorbenzol, chloroquines, climbazol, bis(3-fenilsalitsilat) copper, chromate copper and zinc, kurane, sulfate copper(II)hydrazine, superbum, collaborated, tapentadol, zipform, decadentes, Dylan, diplozoon, diclobutrazol, dimethirimol, directon, dinolfo, dinoterb, dipyrithione, datalists, dodici, drazoxolon, EBP, Eastern steppe biodiversity, itaconate, etem, Amirim, fenaminosulf, verapamil, penetapan, flutrimazole, percarbonic, vorconizole, vorconizole-CIS, pharmacyclics, furofenac, gliadin, griseofulvin, galakrond, Hercules 3944, hexylthio, ICIA0858, Etampes, isovaleric is, mobinil, mechanised, metacoxae, mefenoxam, dicyandiamide methylmercury, metalhawk, Milner, mucochloric anhydride, mickleton, N-3,5-dichlorophenylisocyanate, N-3-nitrophenylacetic, natamycin, N-ethylmercury-4-toluensulfonyl, bis(dimethyldithiocarbamate) Nickel, OCH, dimethyldithiocarbamate finalstate, nitrate of finalstate, forgiven, protocorm; protocare hydrochloride, percarbonic, perigenital, piroxicam, proxyfor, quinazol; quinazol-sulfate, quinizarin, quinceanos, rabenasolo, salicylanilide, SSF-109, soultrain, decorum, mediflor, tilian, teacherpupil, thiophanate tioclinux, dioxime, triamides, clarinol, triazolyl, trihemic, urbicide, XRD-563 and Suriname, IK-1140, NC-224, and combinations thereof.

Additional compounds according to the present invention can be combined with other pesticides, including insecticides, nematicides, miticide, arthropodicides, bactericides or combinations thereof that are compatible with the compounds according to the present invention in the medium selected for application, and help counteract the activity of these compounds, with the formation of their pesticide mixtures and synergistic mixtures. Fungicidal compounds according to the present invention can be applied together with one or more other pesticides to control a wide range of junk, is agricultural purpos the agricultural pests. When the compounds are used together with other pesticides, we state here the connection can be obtained in the form of a composition with another pesticide (pesticide), mix in the tank with the other pesticide (pesticide) or applied sequentially with the other pesticide (pesticide). Typical insecticides include, but are not limited to: antibiotic insecticides such as allocatedin and thuringiensis; macrocyclic lactonase insecticides, such as spinosad; avermectin insecticides such as abamectin, doramectin, emamectin, eprinomectin, ivermectin and selamectin; milbemycin insecticides, such as leemartin, milbemectin, milbemycin and moxidectin; arsenic insecticides, such as calcium arsenate, acetoarsenite copper, copper arsenate, arsenate of lead, potassium arsenite and sodium arsenite; vegetable insecticides, such as anabasine, azadirachtin, d-limonene, nicotine, pyrethrins, cenerini, cinerin I, cinerin II, jasmolin I, jasmolin II, pyrethrin I, pyrethrin II, quassia, rotenon, ryania and sabadilla; urethane insecticides, such as bendiocarb and carbaryl; benzophenonetetracarboxylic insecticides, such as benfuracarb, carbofuran, carbosulfan, carbofuran and furathiocarb; dimethylcarbamate insecticides Dimitar, dimetilan, givingher and pirimicarb; oxycarbonate insecti the IDA, such as alankar, aldicarb, aldoxycarb, butocarboxim, butoxycarboxim, methomyl, nitrilases, oxamyl, Casimir, dicarboxy, thiodicarb and thiofanox; phenylmercuriborate insecticides, such as allistar, aminocarb, bofenkamp, betacar, carbanilate, cloethocarb, dicresyl, dioxane, EMPC, ethiofencarb, fanmakers, fenobucarb, isoprocarb, methiocarb, metolcarb, mexacarbate, bromacil, promecarb, propoxur, trimeter, XMC and killchar; dinitrophenol insecticides, such as dynex, dynapro, dinoseb and DNOC; fluorine-containing insecticides such as barium fluorosilicate preparation, cryolite, sodium fluoride the sodium fluorosilicate preparation and sulfluramid; formamidine insecticides, such as amitraz, Chlordimeform, formetanate and formparent; insecticides-fumigants, such as Acrylonitrile, carbon disulfide, carbon tetrachloride, chloroform, chloropicrin,pair-dichlorobenzene, 1,2-dichloropropane, ethyl formate, ethylenedibromide, ethylene dichloride, ethylene oxide, hydrogen cyanide, logmean, methyl bromide, methyl chloroform, methylene chloride, naphthalene, phosphine, sulfuretted and tetrachlorethane; inorganic insecticides, such as borax, calcium polysulfide, copper oleate, chloride mercury (I), potassium thiocyanate and sodium thiocyanate; chitin synthesis inhibitors, such as bistriflate, buprofezin, chlorfluazuron, cyromazine, diflubenzuron, flotillas is Ron, flufenoksuron, hexaflumuron, lufenuron, novaluron, noviflumuron, enflurane, teflubenzuron and triflumuron; imitators of juvenile hormones, such as epitonin, fenoxycarb, hydroprene, CANopen, methoprene, pyriproxyfen and triplen; juvenile hormones such as juvenile hormone I, juvenile hormone II and juvenile hormone III; agonists of molting hormones, such as chromafenozide, halogenated, methoxyfenozide and tebufenozide; moulting hormones such as α-Edison and ecdysterone; moulting inhibitors such as giovanola; prikazani, such as precoce I, precoce II and precoce III; not assigned to a certain category of the insect growth regulators, such as dicyclanil; insecticides-analogues of nereistoxin, such as bensultap, cartap, thiocyclam and thiosulfat; nicotinoid insecticides, such as flonicamid; nitroguanidine insecticides, such as clothianidin, dinotefuran, Imidacloprid and thiamethoxam; nitromethylene insecticides, such as nitenpyram and nithiazine; pyridylmethylamine insecticides such as acetamiprid, Imidacloprid, nitenpyram and thiacloprid; organochlorine insecticides, such as bromo-DDT, camphechlor, DDT, pp'-DDT ethyl-DDD, HCH, gamma-HCH, lindane, Methoxychlor, pentachlorophenol and TDE; cyclodiene insecticides such as Aldrin, bromocyclen, chlorobicyclo, chlordane, Chlordecone, dieldrin, dilor, endosulfan, endrin, HED, heptachlor, HHDN, isobenzan, Isodrin, kelevan and mirex; fosfororganichyeskii insecticides, such as pumpevents, chlorfenvinfos, crotoxyphos, dichlorvos, dicrotophos, dimethylene, pospert, heptenophos, Metacritic, mevinphos, monocrotophos, naled, naftalis, phosphamidon, propafol, TEPP and tetrachlorvinphos; thiophosphoramidate insecticides, such as dioxybenzone, tomatlan and pintout; aliphatic thiophosphoramidate insecticides, such as action, Amiton, cadusafos, chlorethoxyfos, chlormephos, deletion, demephion-O, demephion-S, demeton, demeton, demeton-S, demeton-methyl, demeton-O-methyl, demeton-S-methyl, demeton-S-methylsulfone, disulfoton, ethion, ethoprophos, IPSP for acquiring, isocial, Malathion, methacrifos, oxydemetonmethyl, oxidation, oxydisulfoton, Fort, sulfotep, terbufos, thiometon; aliphatic amide thiophosphoramidate insecticides, such as amidation, zantout, dimethoat, athotmail, formation, mecarbam, omethoate, procoat, sofabed and validation; Aksinya thiophosphoramidate insecticides, such as chlorphoxim, phoxim and taximeter; heterocyclic thiophosphoramidate insecticides, such as azamethiphos, coumaphos, comitat, dioxathion endation, Manson, porpotion, fozalon, pyraclofos, predatation and himation; benzothiophene thiophosphoramidate insecticides, such as demicrats and t is cropos; benzotriazine thiophosphoramidate insecticides, such as azinphos-ethyl and azinphos-methyl; isoindoline thiophosphoramidate insecticides, such as dialifos and phosmet; isoxazoline thiophosphoramidate insecticides, such as isoxathion and sulprofos; pyrazolopyrimidinone thiophosphoramidate insecticides, such as chlorpropham and pyrazophos; pyridine thiophosphoramidate insecticides, such as chlorpyrifos and chlorpyrifos-methyl; pyrimidine thiophosphoramidate insecticides, such as butamifos, diazinon, etrimfos, liempo, pirimiphos-ethyl, pirimiphos-methyl, presidios, perimeter and tebupirimfos; hinoksalinovym thiophosphoramidate insecticides, such as Hidalgos and finalpos-methyl; thiadiazoline thiophosphoramidate insecticides, such as amidation, litigation, mitigation, protection; triazole thiophosphoramidate insecticides, such as isazofos and triazophos; phenyl thiophosphoramidate insecticides, such as attout, bromophos, bromophos-ethyl, carbophenothion, chlorthiophos, cyanophos, cetiat, deception, dichlofenthion, Etats, famphur, fenchlorphos, fenitrothion, fensulfothion, fenthion, fenthion-ethyl, heteropus, idents, resolvents, parathion, parathion-methyl, phenkapton, fossiler, profenofos, prothiofos, sulprofos, temephos, trichlormethane-3 and tritanopes; phosphonate and tacticity, such as Boutonnat and trichlorfon; phosphorothioate insecticides, such as MegaFon; phenylethylenediamine insecticides, such as fonofos and trichloronat; phenyltrichlorosilane insecticides, such as cyanofenphos, EPN and leptophos; phosphoramidate insecticides, such as crufomate, fenamiphos, pastilan, mephosfolan, phosfolan and perimeters; phosphoramidothioate insecticides, such as Arafat, isocarbophos, isofenphos, methamidophos and propetamphos; phosphorodiamidate insecticides, such as dimefox, masimax, metafox and Srdan; oxadiazine insecticides, such as indoxacarb; phthalimide insecticides, such as dialifos, phosmet and tetramethrin; pyrazol insecticides, such as acetarsol, ethiprole, fipronil, perflubron, periphral, tebufenpyrad, toppenberg and unilibro; insecticides on the basis of PYRETHROID esters, such as acrinathrin, allethrin, bioallethrin, Bartin, bifenthrin, bioeconomical, cyclotron, cicloprofen, cyfluthrin, beta-cyfluthrin, cigalotrin, gamma cigalotrin, lambda cigalotrin, cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, Zeta-cypermethrin, cyphenothrin, deltamethrin, dimefluthrin, demetrin, empenthrin, fenfluthrin, generatin, fenpropathrin, fenvalerate, esfenvalerate, flucythrinate, fluvalinate, Tau-fluvalinate, pyrethrin, imiprothrin, metofluthrin, permethrin, bioperl is Rin, transpermethrin, phenothrin, prallethrin, perflutren, prismatron, resmethrin, bioresmethrin, resmethrin, tefluthrin, tarletan, tetramethrin, tralomethrin and transfluthrin; insecticides on the basis of PYRETHROID ethers, such as etofenprox, flavandiols, halftracks, protrient and selflove; pyrimidinamine insecticides, such as lufenuron and pyrimidifen; pyrrole insecticides, such as chlorfenapyr; insecticides on the basis of tetronic acids, such as spiromesifen; insecticides on the basis of thiourea, such as diafenthiuron; insecticides on the basis of urea, such as flucturion and sulcofuron; and insecticides, are not classified in a certain category, such as closantel, crotamiton, EXD, pensator, tenoxicam, flubendiamide, hydramethylnon, isoprothiolane, malaanonan, metaflumizone, methoxamine, diflouride, pyridaben, pyridalyl, rafoxanide, triuralin and triazamate, and combinations thereof.

Additional compounds according to the present invention can be combined with herbicides that are compatible with the compounds according to the present invention in the medium selected for application, and are not antagonistic to the activity of these compounds in the formation of pesticide mixtures and their synergistic mixtures. To combat a wide range of undesirable plants fungicidal compounds which ia according to the present invention can be applied together with one or more herbicides. When the compounds are used in conjunction with herbicides, declare here the connection can be obtained in the form of a composition containing herbicide (herbicide), mix in the tank with herbicide (herbicide) or applied sequentially with a herbicide (herbicide). Typical herbicides include, but are not limited to:amide herbicidessuch as ellidaar, beflubutamid, betadex, benzidin, bromobutyl, cafestol, CDEA, chlorine, cobresol, dimethenamid, dimethenamid-P, diphenamid, aprons, atiprimod, phentramin, flupoxam, fomesafen, galasoft, isosorbid, isoxaben, napropamide, naptalam, pethoxamid, propyzamide, heroname and tabulam;anilide herbicidessuch as chloranil, zizanie, clomipram, cipramil, diflufenican, etamesonic, tenaculum, flufenacet, flufenisal, mefenacet, mefluidide, meramipop, monolid, nitroanilide, pantanagar, picolinafen and propanil;Alliluyeva herbicidessuch as benzoylperoxy, planrep and planrep-M;chloroacetanilide herbicidessuch as acetochlor, alachlor, butachlor, buenaflor, delaflor, diacetyl, dimethachlor, metazachlor, metolachlor, S-metolachlor, pretilachlor, propachlor, propisochlor, panahar, turbuhaler, tanishlar and silahlar;sulfonanilide herbicidessuch as bestfloor, perfsuite, perimacular and proplusr;sulfonamidnuyu herbicide is such as Azul, carbazoles, tenaculum and oryzalin;antibiotic herbicidessuch as milanapos;herbicides based on benzoic acidsuch as chloramben, dicamba, 2,3,6-TBA and takamba;herbicides based on pyrimidinemethanol acidsuch as bispyribac and Perminova;herbicides based on pyrimidinediamine acidsuch as pyrithiobac;herbicides based on phthalic acidsuch as chlorthal;herbicides based on pikolinos acidsuch as aminopyralid, clopyralid and picloram;herbicides based on quinoline-carboxylic acidsuch as chinkara and hinnerk;arsenic herbicidessuch as cakaudrove acid, CMA, DSMA, hexaplorum, MAA, MAMA, MSMA, arsenite of potassium and sodium arsenite;benzoylacetonate herbicidessuch as mesotrione, sulcotrione, deforestion and tembotrione;bezoperatsionnye herbicidessuch as belforest and ethofumesate;urethane herbicidessuch as Azul, carbocat, chlorproma, dichlormid, tenaculum, carbocylic and thermocarb;carbanilate herbicidessuch as Barban, BCPC, carbazoles, carbetamide, CEPC, chlorbutol, chlorpropham, CPPC, desmedipham, Fenicia, phenmedipham, phenmedipham-ethyl, propham and swap;cyclohexenone herbicidessuch as aloxide, butoxide, clethodim, chloroxygen, cyclo is sitting, profoxydim, sethoxydim, tepraloxydim and tralkoxydim;cyclopropylacetylene herbicidessuch as isoxaflutole and isoxaflutole;dicarboximide herbicidessuch as bestindian, cinidon-ethyl, planesin, flumiclorac, flumioxazin and flubiprofen;dinitroaniline herbicidessuch as benfluralin, Butylin, dinitramine, ethalfluralin, fluchloralin, isopropylene, methylpropan, nicraly, oryzalin, pendimethalin, prodiamine, propleuron and trifluralin;dinitroaniline herbicidessuch as dinofest, dynapro, dinoseb, dinoseb, dinoterb, DNOC, aminofen and medinotes;herbicides based on simple diphenyl ethersuch as amoxifen;herbicides based on simple nitrophenylamino ethersuch as acifluorfen, klonipin, bifenox, chlorethoxyfos, chlornitrofen, atiprimod, forgiven, verglichen, Thornicroft, fomesafen, voreloxin, galasoft, lactofen, nitrofen, nitrofluorene and oxyfluorfen;dithiocarbamate herbicidessuch as dazomet and methamphetamine;halogenated aliphatic herbicidessuch as lorac, chlorophos, dalapon, fluprofen, hexachloroacetone, logmean, bromide, monochloracetic acid, SMA and TCA;imidazolinone herbicidessuch as imazamethabenz, imazamox, imazapic, imazapyr, imazaquin and imazethapyr;inorganic herbicidessuch ka is sulpham ammonium, borax, chlorate calcium, copper sulfate, iron sulfate (II), potassium azide, potassium cyanate, sodium azide, sodium chlorate and sulfuric acid;nitrile herbicidessuch as bromophenyl, bromoxynil, chloroxine, dichlobenil, iodobenzyl, ioxynil and PERCHLORYL;organophosphorus herbicidessuch as lipophos-methyl, anilofos, bensulide, milanapos, butamifos, 2,4-DEP, DMPA, EBEP, fosamine, glufosinate, glyphosate and piperophos;phenoxy-herbicidessuch as bromophenoxy, clomipram, 2,4-DEB, 2,4-DEP, divinamente, dial, Arbon, atiprimod, interacial and Triforce;ferociously herbicidessuch as 4-CPA, 2,4-D, 3,4-DA, MCPA, MCPA-thioethyl and 2,4,5-T;proximally herbicidessuch as 4-CPB, 2,4-DB, 3,4-DB, MCPB and 2,4,5-TB;phenoxypropionate herbicidessuch as laprop, 4-CPP, dichlorprop, dichlorprop-P, 3,4-DP, fenoprop, mecoprop and mecoprop-P;aryloksyfenoksypropionowe herbicidessuch as lorazepam, clodinafop, cloop, cyhalofop, diclofop, fenoxaprop, fenoxaprop-P, pentiumpro, fluazifop, fluazifop-P, haloxyfop, galaxy-P, isocaporate, meramipop, propaquizafop, hisamoto, hisamoto-P and triphop;phenylendiamine herbicidessuch as dinitramine and prodiamine;pyrazolidine herbicidessuch as benzien, pyrazoline, pyrasulfotole, paradoxien, pyroxsulam and topramezone;pyrazolidinone herbicidessuch as flatlet and is iraflores; pyridazinone herbicidessuch as creatin, perinatal and peridot;pyridazinone herbicidessuch as Bremerton, ozone chloride, dimeadozen, flutter, matterson, norflurazon, oxadiazon and pidyon;pyridine herbicidessuch as aminopyralid, clidanac, clopyralid, dithiopyr, fluroxypyr, galaxidi, picloram, picolinafen, pericar, thiazopyr and triclopyr;pyrimidinediamine herbicidessuch as primidon and toclaim;herbicides based on Quaternary ammonium compoundssuch as cybercat, ditambah, difenzoquat, Diquat, Mohammad and paraquat;THIOCARBAMATE herbicidessuch as butyl, cycloate, diallate, EPTC, asbroker, etiolate, itprint, Mediobanca, molinet, arrancars, pebulate, prosulfocarb, perimutter, sulfallate, thiobencarb, thiocarbonyl, triallate and vernolate;THIOCARBAMATE herbicidessuch as dioxane, EXD and proxy;herbicides based on thioureasuch as meteoron;triazine herbicidessuch as DIPROPYLENE, triazolam and trihydroxystearin;chlorotriazine herbicidessuch as atrazine, Chorazin, cyanazine, ziprin, Eglinton, Ipsen, metabrain, prolatin, progenesis, propazine, subutility, Simazine, terbutylazine and triacetin;methoxythiazole herbicidessuch as atraton, Mahometan, prometon, sebumeter, Simeon and Ter is umeton; methyltetrazole herbicidessuch as ametrine is high, isoprotein, centrin, desmetryn, deltamethrin, melipramin, prometryn, simetryn and terbutryn;triazinone herbicidessuch as ameridian, libusin, hexazinone, isomerizing, metamitron, metribuzin;triazole herbicidessuch as amitrol, cafestol, aprons and flupoxam;triazolinone herbicidessuch as nicarbazin, Banjarmasin, carfentrazone, flucarbazone, propoxycarbazone, sulfentrazone and thiencarbazone-methyl;triazolopyrimidine herbicidessuch as karasulu, dicloflam, florasulam, flumetsulam, metosulam, penoxsulam and pyroxsulam;brazillia herbicidessuch as butoverall, bromacil, flourophenyl, isocal, lenacil and terbacil;3-phenylurazole;herbicides urea-basedsuch as benzthiazole, cumyluron, cyclotron, dichloramine, diflubenzuron, Sonoran, Sauron, methabenzthiazuron, monitoron and narure;herbicides based on prilocainesuch as ensure, butuan, chlorbromuron, chlorimuron, chlortoluron, chloroxuron, dameron, Difenoxin, dimefuron, Diuron, fenuron, fluometuron, Flatiron, Isoproturon, linuron, meturon, methyldibromo, metaventure, metobromuron, metoxuron, monolinuron, monuron, neburon, perfluro, finansure, sibron, tetraplodon and thidiazuron;herbicides OS is ove pyrimidinylpiperazine such as amidosulfuron, azimsulfuron, encultured, chlorimuron, cycloaliphatic, ethoxysulfuron, flazasulfuron, placetocolumn, flupyrsulfuron, foramsulfuron, halosulfuron, imazosulfuron, metsulfuron, nicosulfuron, orthosulfamuron, oxasulfuron, primisulfuron, pyrazosulfuron, rimsulfuron, sulfometuron, sulfosulfuron and trifloxysulfuron;herbicides based on triethynylbenzenesuch as chlorsulfuron, chinaculture, atomiculture, iodosulfuron, metsulfuron, prosulfuron, thifensulfuron, triasulfuron, tribenuron, triflusulfuron and tritosulfuron;herbicides basedthiadiazolidinesuch as butiran, tidiman, tebuthiuron, diazafluoren and thidiazuron; andherbicides are not classified in a certain categorysuch as acrolein, allyl alcohol, azafenidin, benazolin, bentazon, benzamycin, booteasy, calcium cyanamide, Cambodian, chlorgenic, jarvenpa, chlorfluazuron, chlorflurazole, cinmetacin, clomazone, CPMF, cresol,ortho-dichlorobenzene, timepart, endothal, fluorometer, floridon, flurochloridone, flurtamone, fluthiacet, indianian, metasol, methylisothiocyanate, snipercraft, OCH, oxadiargyl, oxadiazon, oxacyclobutane, pentachlorophenol, phenoxazone, acetate finalstate, pinoxaden, prosulfuron, perbenzoic, piritramid, girolami is, redetail, sulpician, thidiazuron, tridiphane, treemature, tripropionin and tritak.

Another variant implementation of the present invention is a method of combating fungi or way to prevent fungi. This method includes applying to the soil, plant, roots, leaves, seeds or location fungi or the location where you want to prevent the fungus (for example, drawing on cereal plants or vine), fungicide effective amount of one or more compounds of formula I. Compounds suitable for treatment of various plants when fungicide acceptable levels, and at the same time they are low phytotoxicity. The compounds can be applied as a protectant and/or as eradicant.

It is established that the compounds possess significant antifungal activity, particularly for agricultural use. Most of the compounds are particularly effective for use in agricultural crops and garden plants.

Specialists in this field will be clear that the effectiveness of the compounds in the above-mentioned fungi defines the General applicability of these compounds as fungicides.

The compounds possess a wide spectrum of activity against pathoge the different fungi. Typical pathogens may include, but is not limited to, pathogens causing spot blotch of wheat (Septoria tritici, also known asMycosphaerella graminicola), scab of Apple (Venturia inaequalis) and Cercospora leaf sugar beet (Cercospora beticola), peanuts (Cercospora arachidicolaandCercosporidium personatum) and other crops, and black ' drive from sigatoka of bananas (Mycosphaerella fujiensis). The exact amount of the active substance for application depends not only on the specific active substance to be applied, but also from the desired specific actions, species of fungi, with whom we have to fight, and the stages of their growth, as well as from parts of the plant or other product that is exposed to contact with the connection. Thus, all of the compounds and compositions containing them may not be equally effective at similar concentrations or against the same species of fungi.

The compounds are effective when applied to plants for the containment of disease and botanically acceptable number. The term "containment of disease and botanically a reasonable amount" refers to the amount of compound that kills or inhibits disease of plants in respect of which the required combat fungi, but is not significantly toxic to plants. This number will usually be accounted for shall be from approximately 0.1 to approximately 1000 hours/million (ppm), preferably from 1 to 500 hours/million Exact concentration of the desired compound varies depending on fungal that you are fighting, the type of composition, method of application, specific plant species, climatic conditions, etc. a Suitable application rate is typically in the range from approximately 0.10 to approximately 4 lbs/acre (approximately from 0.01 to 0.45 grams per square meter, g/m2).

Any given range or desired value can be extended or changed without losing the desired effects, as is obvious to a person skilled in the art to understand here is the description.

The compounds of formula I can be obtained by using well-known chemical procedures. Intermediate products not specifically mentioned in this description are commercially available and can be obtained using the steps described in the chemical literature methods, or can be easily synthesized from commercially available starting compounds using standard procedures.

The following examples are provided to illustrate various aspects of the compounds according to the present invention and should not be construed as limiting the claims.

Examples

Getting 5-fluoro-2-(4-forbindelse)pyrimidine-4-amine (1):

To a solution of 4-fermentelos alcohol (2,56 g, 20.3 mmol) in 1,4-dioxane (20 ml) for 10 min in several portions was added 60% NaH (0,813 g, 20.3 mmol). To the obtained solution under stirring with a magnetic stir bar was added 2-chloro-5-ftorpirimidinu-4-amine* (2.00 g, to 13.6 mmol) and the mixture was stirred at room temperature until, until there is no further gas evolution. Then the reaction mixture was heated in a microwave reactor CEM Discover at 120°C for 90 minutes the Cooled reaction mixture was distributed between ethyl acetate and water, the organic phase is concentrated and the product was purified by column chromatography (gradient hexane/ethyl acetate)to give 5-fluoro-2-(4-forbindelse)pyrimidine-4-amine (1.66 g, yield 52%) as a solid white color: TPL (melting point) 129-131°C;1H NMR (300 MHz, CDCl3) δ to $ 7.91 (d, J=2.6 Hz, 1H), 7,42 (m, 2H), 7,03 (m, 2H), 5,27 (s, 2H), of 5.05 (Sirs, 2H); MS (ESI)m/z238 (M+H)+

*4-amino-2-chloro-5-ftorpirimidinu can be purchased commercially or obtained using known literature methods.

1. Hayashi, T.; Kawakami, T., Japanese patent JP 2005126389

2. Durr G.J.J. Med. Chem.1965, 8(2), 253.

2-(3-Bromobenzylamine)-5-ftorpirimidinu-4-ylamine (2):

To a mixture of KO-t-Bu (1,0 M intBuOH, of 1.36 ml of 1.36 mmol) under stirring with a magnetic stirrer was added 3-bromophenyl)methanol (0.25 g, 1,36 the mol). To the resulting solution were added 2-chloro-5-ftorpirimidinu-4-ylamine (0.10 g, of 0.68 mmol), the mixture was closed with a stopper and stirred at 90°C for 4 hours. The reaction mixture was cooled to room temperature, diluted with water and the precipitate was collected by filtration. The solid is washed with water, washed with cyclohexane and dried in a vacuum drying Cabinet. A solution of the compound in CH2Cl2was loaded into the column, Biotage SCX and suirable CH2Cl2with the subsequent addition of a 2.0 M solution of NH3in MeOH. The solvent is evaporated under reduced pressure, thus obtaining specified in the header connection (0,100 g, 49%) as a solid substance not quite white: TPL 143-145°C;1H NMR (400 MHz, DMSO-d6) δ of 7.90 (d, J=2.5 Hz, 1H), to 7.61 (s, 1H), 7,43 (d, J=8.0 Hz, 1H), was 7.36 (d, J=7.7 Hz, 1H), 7,22 (t, J=7.7 Hz, 1H), 5,28 (s, 2H), 5,20 (Sirs, 2H); GC-MS (EI)m/z297, 299 (M)+.

Getting 5-fluoro-2-[1-(4-forfinal)ethoxy]pyrimidine-4-ylamine (3):

To a mixture of 4-amino-2-chloro-5-ftorpirimidinu (11,10 g, 75.2 mmol) 1-(4-forfinal)ethanol (11,70 g of 82.8 mmol) under stirring with a magnetic stirrer to one portion was added a 1.0 M solution of KO-t-Bu intBuOH (82,8 ml of 82.8 mmol) and the resulting yellow-brown mixture was heated under reflux and was stirred for 24 hours. The solvent was removed in vacuum and the obtained Krasnogorovka oil was purified flash chromatography (SiO 2, 0→10% MeOH/CH2Cl2), while receiving 5.5 g of red-orange oil. The resulting oil is suspended in a mixture of hexanol (100 ml) and was stirred for 16 hours. To unchanged mixture was added water (100 ml) and vigorously stirred two-phase system within 1 hour. The obtained solid cream color was collected by vacuum filtration, washed with warm water (55°C, 2×100 ml) and dried in vacuum at 55°C for 16 hours, while receiving 5-fluoro-2-[1-(4-forfinal)ethoxy]pyrimidine-4-ylamine (3,30 g, the output of 17.2%) as a solid white color: TPL 96-98°C;1HNMR (300 MHz, CDCl3) δ to 7.84 (d, J=2.6 Hz, 1H), 7,42-7,38 (m, 2H), 7.03 is-6,97 (m, 2H), 5,99 (kV, J=6,6 Hz, 1H), 5,09 (Sirs, 2H), 1,61 (d, J=6.6 Hz, 3H); MS (ESI) m/z 252 (M+H)+, m/z 250 (M-H)-.

Getting 1-phenylethane-O-(4-amino-5-ftorpirimidinu-2-yl)oxime (4):

To a mixture of 4-amino-2-chloro-5-ftorpirimidinu (0.10 g, of 0.68 mmol) and acetophenone (0,092 g of 0.68 mmol) in dry DMF (3 ml) under stirring with a magnetic stirrer in a 5 ml vessel microwave reactor Biotage Iniator was added NaH (0,027 g of 60 wt.% suspension of 0.68 mmol) in an atmosphere of N2. After cessation of gas evolution resulting mixture is hermetically closed by a cover with an aperture microwave reactor Biotage Initiator and heated in a microwave reactor Biotage Initiator to 100°C for 60 minutes. The contents of the vessel were poured into PR the tag with water (5 ml) and CH 2Cl2(5 ml) and neutralized with a few drops of 2N HCl solution. The phases were separated and the organic extract was dried over MgSO4, was filtered and was evaporated in a stream of nitrogen. Raw (untreated) content was purified on silica (gradient EtOAc/hexane) was evaporated and the obtained fractions, while receiving 0,057 g (34%) 1-phenylethane-O-(4-amino-5-ftorpirimidinu-2-yl)oxime in the form of solid substances not quite white: TPL 163-165°C;1H NMR (300 MHz, CDCl3) δ of 8.04 (d, J=2.6 Hz, 1H), to 7.75 (m, 2H), 7,42 (m, 3H), 5.25-inch (Sirs, 2H), of 2.51 (s, 3H); HPLC-MS (ESI)m/z247 (M+H)+.

Getting 5-fluoro-2-(thiophene-2-ylethoxy)pyrimidine-4-ylamine (5):

To a mixture of 2-chloro-5-ftorpirimidinu-4-ylamine (2.00 g, 13.5 mmol) and thiophene-2-ylmethanol (1.92 g, to 16.9 mmol) with magnetic stir bar in a 20 ml microwave reaction vessel reactor Biotage Initiator was added KO-tBu in (17.0 ml of a 1M solution intBuOH, of 17.0 mmol). The resulting mixture is hermetically closed by a cover with an aperture microwave reactor Biotage Initiator and heated in a microwave reactor Biotage Initiator to 100°C for 30 min Cycle heating was repeated (2×)to the total reaction time was 90 minutes the Contents of the vessel were poured into ice water, and using 2N HCl solution was brought to pH to neutral values. The obtained solid was filtered and washed with water (2×) and then 20%of the second mixture of simple ether/hexane (100 ml). The remaining solid was dried over night at 50°C in vacuum, while receiving of 4.17 g (68%) of 5-fluoro-2-(thiophene-2-ylethoxy)pyrimidine-4-ylamine in the form of powder light yellow color: TPL 92-94°C;1H NMR (300 MHz, CDCl3) δ a 7.92 (d, J=2.7 Hz, 1H), 7,29 (m, 1H), 7,13 (d, J=3.6 Hz, 1H), 6,97 (m, 1H), 5,46 (s, 2H), 5,17 (Sirs, 2H); MS (ESI)m/z226 (M+H)+.

Obtaining N-[5-fluoro-2-(thiophene-2-ylethoxy)pyrimidine-4-yl]ndimethylacetamide (6):

In the test tube with screw cap volume 2 drachmas was treated with a solution of 5-fluoro-2-(thiophene-2-ylethoxy)pyrimidine-4-ylamine (0.10 g, 0.4 mmol) in CH2Cl2acetylchloride (0,032 g, 0.4 mmol) and PS-NMM (0,42 g, 0.8 mmol), polimersvarka equivalent toNmethylmorpholine (NMM). The mixture was stirred at room temperature for 12 hours. The reaction mixture was filtered and the solvent evaporated, thus obtaining 0,084 g (75%) indicated in the title compounds as white solids: TPL 134-136°C;1H NMR (300 MHz, CDCl3) δ 8,24 (d, J=2.6 Hz, 1H), 7,86 (Sirs, 1H), 7,31 (m, 1H), 7.23 percent (m, 1H), 7,00 (m, 1H), 5,54 (s, 2H), 2,58 (s, 3H); MS (ESI)m/z268 (M+H)+.

Obtain [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]-(4-methylpiperazin-1-ylmethyl)amine (7):

To a mixture of paraformaldehyde (0.24 g, 8 mmol) in CH2Cl2(20 ml) under stirring with a magnetic stirrer was addedNmethylpiperid is in (0,80 g, 8.0 mmol). The suspension was stirred on an orbital shaker overnight at ambient temperature and then was added 5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamine (of 0.47 g, 2.0 mmol). The resulting mixture was stirred from Friday to Monday at room temperature. The solvent is evaporated and the raw (untreated) residue was twice washed with 50%mixture of simple ether/petroleum ether and dried in a stream of N2while receiving 0.21 g (30%) [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl](4-methylpiperazin-1-ylmethyl)amine in the form of a solid beige color: TPL 125-126°C;1H NMR (300 MHz,CDCl3) δ 7,83 (d, J=2.3 Hz, 1H), 7,43 (m, 2H), 7,03 (t, J=8.5 Hz, 2H), 5.40 to (Sirs, 1H), 5,27 (s, 2H), to 4.41 (d, J=6,8 Hz, 2H), 2.63 in (Sirs, 4H), 2,47 (Sirs, 4H), of 2.30 (s, 3H); HPLC-MS (ESI)m/z350 (M+H)+.

Obtain [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]triethylenemelamine (8):

To a mixture of 5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamine (0.25 g, 1.05 mmol) in dry THF (5 ml) under stirring with a magnetic stirrer at 0°C was added NaH (0,042 g of 60 wt.% suspension in mineral oil, 1.05 mmol). When the bubbling gas was stopped, with a syringe dropwise (neat) was added triethylsilane (0,158 g, 1.05 mmol). After stirring overnight at ambient temperature the reaction mixture was poured into a simple ether and washed smesovaciho saturated sodium bicarbonate solution and saturated salt solution. The organic layer was separated, dried over Na2SO4, filtered and evaporated, thus obtaining a solid white color. The resulting crude (crude substance was purified on silica using column chromatography (gradient EtOAc/hexane), while receiving 0,121 g (33%) [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]triethylenemelamine in the form of a clear yellow oil:1H NMR (300 MHz, CDCl3) δ 7,89 (d, J=2.5 Hz, 1H), 7,39 (m, 2H), 7,03 (t, J=8.6 Hz, 2H), 5,27 (s, 2H), 4.53-in (s, 1H), 0,99 (m, 9H), or 0.83 (m, 6H); HPLC-MS (ESI)m/z352 (M+H)+.

Obtaining complex 4-fortunelounge ester [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]bicarbonates acid (9):

To a cooled ice mixture of 5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamine (0.25 g, 1.05 mmol) in dry THF (5 ml) under stirring with a magnetic stirrer was added NaH (0,042 g of 60 wt.% suspension in mineral oil, 1.05 mmol). After the bubbling gas was stopped, was added dropwise 4-ftorhinolonami (0,184 g, 1.05 mmol) in solution in dry THF. After stirring for one hour the reaction mixture was distributed between EtOAc and a saturated solution of salt. The organic extract was dried over Na2SO4, was filtered and was evaporated. Raw (untreated) material was purified on silica using a gradient of EtOAc/Hex and then MeOH/EtAc, while receiving 0,054 g (14%) complex 4-fortunelounge ester [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]bicarbonates acid in a solid white color: TPL 103-105°C;1H NMR (300 MHz, CDCl3) δ 8,58 (d, J=2.2 Hz, 1H), 7,43 (m, 2H), was 7.08 (m, 10H), of 5.40 (s, 2H); HPLC-MS (ESI)m/z514 (M+H)+.

Getting complicated phenyl ester [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]carbamino acid (10):

With stirring to a mixture of 5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamine (0.20 g, 0.84 mmol) in dry THF (3 ml) at the temperature of the ice bath was added NaH (0,034 g of 60 wt.% suspension in mineral oil, 0.84 mmol). When the bubbling gas was stopped, the mixture via cannula transferred (dropwise) with stirring, cooled in ice, the mixture diphenylcarbonate (1.8 g, 8.4 mmol) in dry THF (5 ml). The mixture was stirred overnight, poured into EtOAc and washed with saturated aqueous NH4Cl followed by washing with a saturated solution of salt. EtOAc layer was separated, dried over Na2SO4, was filtered and was evaporated. Raw (untreated) material was purified on silica gel using a gradient of EtOAc and the mixture of hexanol and while receiving 0,063 g (21%) complicated phenyl ester [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]carbamino acid in a solid white color: TPL 129-131°C;1 H NMR (300 MHz, CDCl3) δ of 8.28 (d, J=2.3 Hz, 1H), 7,43 (m, 5H), 7,30-7,20 (m, 2H), 7,02 (t, J=8.6 Hz, 2H), 5,38 (s, 2H); HPLC-MS (ESI)m/z358 (M+H)+.

Obtaining complex ethyl ester of N-[5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]assalamou acid (11):

To a mixture of 5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamine (0,235 g 0,99 mmol),Nmethylmorpholine polystyrene (0,538 g of 1.24 mmol) and CH2Cl2(5 ml) was added complicated ethyl ester Chlorococcales acid (is 0.135 g, 0,99 mmol) and the resulting mixture was stirred on an orbital shaker for 16 hours. The reaction contents were filtered on acid SPE cartridge and suirable CH2Cl2. CH2Cl2the filtrate was evaporated, thus obtaining 0,165 g (50%) of a compound ethyl ester of N-[5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]assalamou acid in the form of a clear oil:1H NMR (300 MHz, CDCl3) δ of 9.21 (Sirs, 1H), scored 8.38 (d, 7=2.3 Hz, 1H), of 7.48 (m, 2H), 7,03 (t, J=8.5 Hz, 2H), of 5.40 (s, 2H), 4,48 (kV, J=7,1 Hz, 2H), 1,45 (t, J=7,1 Hz, 3H); HPLC-MS (ESI)m/z338 (M+H)+.

Obtain [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]amide 3,4-dichloroisothiazol-5-carboxylic acid (12):

To a suspension of 3,4-dichloroisothiazol-5-carboxylic acid (0.15 g, from 0.76 mmol) in oxanilide (2 ml) was added a catalytic amount of dimethylformamide (2 drops) and the mixture was heated to 80 the C and was stirred for 2 hours. Excess oxalicacid was removed on a rotary evaporator. Meanwhile, 5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamine (0.17 g, of 0.68 mmol) was dissolved in THF (1 ml)was treated with LiHMDS (1 M solution in THF, 0.76 to ml, from 0.76 mmol) and was stirred for 10 minutes. Was added freshly prepared 3,4-dihlotiazid-5-carbonylchloride*dissolved in THF (1 ml), the reaction mixture was closed with a stopper and was stirred for 12 hours. The reaction mixture was diluted with water and the desired compound was extracted with CH2Cl2(3×5 ml). The combined extracts were dried over MgSO4and then was evaporated under reduced pressure. The mixture was suirable CH2Cl2through anion-exchange column for solid phase extraction and then further purified by chromatography with reversed phase, while receiving [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]amide 3,4-dichloroisothiazol-5-carboxylic acid (0.035 g, 12%) as a solid, yellowish-brown: TPL 87-90°C;1H NMR (400 MHz, DMSO-d6) δ 11,78 (s, 1H), 8,67 (s, 1H), 7,51-of 7.48 (m, 2H), 7.24 to 7,19 (m, 2H, in), 5.25 (s, 2H); MS (ESI)m/z417 (M+H)+, 415 (M-H)-.

*Nagata, T.; Kogure, A.; Yonekura, N.; Hanai R.; Kaneko L; Y. Nakano, Japanese patent JP 2007211002 A

Getting diethyl ether complex [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]phosphoramidite acid (13):

To a solution of 5-fluoro-2-(4-forbindelse)pyrimi the Jn-4-ylamine (0.10 g, 0.42 mmol) in dry THF (5 ml) under stirring with a magnetic stirrer under nitrogen atmosphere was added NaH (0,017 g of 60 wt.% suspension, 0.42 mmol) and stirred the mixture until then, until it stopped bubbling gas. Was added dropwise diethylphosphate (0,073 g, 0.42 mmol) and stirred the mixture at ambient temperature for 1 hour. The reaction mixture was evaporated to dryness, the residue was dissolved in EtOAc and washed with saturated aqueous NH4Cl. The organic layer was separated, dried over Na2SO4, was filtered and was evaporated. Raw (untreated) material was purified on silica (gradient acetone/CH2Cl2), while receiving 0,017 g (11%) diethyl ether complex [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]phosphoramidite acid in a solid white color: TPL 109-111°C;1H NMR (300 MHz, CDCl3) δ 8,10 (t, J=1.8 Hz, 1H), 7,43 (m, 2H), 7,03 (t, J=8.5 Hz, 2H), 6,18 (Sirs, 1H), to 5.35 (s, 2H), 4,25 (m, 4H), to 1.38 (t, J=7,1 Hz, 6H); HPLC-MS (ESI)m/z374 (M+H)+.

Obtain [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]-(1-methoxypropyl)amine (14):

To a solution of 5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamine (0.10 g, 0.42 mmol) in Propionaldehyde (2 ml) was added a catalytic amount camphorsulfonic acid. The mixture was stirred on an orbital shaker at room temperature for 4 cha is s and then was evaporated to dryness. Was added methanol (2 ml) and the resulting solution was heated to 60°C for 1 hour. After evaporation the crude product was purified by chromatography with reversed phase, while receiving specified in the header connection (0,030 g, yield 24%) as a clear colorless oil:1H NMR (300 MHz, CDCl3) δ to $ 7.91 (d, J=2.5 Hz, 1H), 7,47-7,41 (m, 2H), 7,09-7,01 (m, 2H), 5,41 (dt, J=9.9 and 6.0 Hz, 1H), and 5.30 (s, 2H), 5,2 (sird, J=10 Hz, 1H), 3,12 (s, 3H), 1,88 is 1.60 (m, 2H), and 0.98 (t, J=7,1 Hz, 3H); HPLC-MS 308 (ES-), 310 (ES+).

Obtain [5-fluoro-2-(4-methylbenzylamino)pyrimidine-4-ylamino]methanol (16):

To a solution of 5-fluoro-2-(4-methylbenzylamino)pyrimidine-4-ylamine (0.10 g, 0.43 mmol) in dioxane (2 ml) was added paraformaldehyde (to 0.060 g, 2 mmol) and the mixture was stirred on an orbital shaker at 90°C for 16 hours, cooled and evaporated to dryness. When cleaning chromatography with reversed phase received 0,070 g (63%) indicated in the title compound in the form of a solid white color: TPL 97-98°C;1H NMR (CDCl3) δ 7,94 (d, J=2.5 Hz, 1H), was 7.36 (d, J=7.9 Hz, 2H), 7,19 (d, J=7.9 Hz, 2H), 5,97 (Sirs, 1H), 5,33 (s, 2H), 5,04-4,99 (m, 2H), 3,39 (t, J=8.0 Hz, 1H), is 2.37 (s, 3H); MS (ESI)m/z264 (M+H)+.

Getting benzoyloxymethyl-[5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]amine (18):

To a mixture of [5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamino]methanol (0.10 g, 3.7 mmol) in benzyl with IRTE (1 ml) was added a catalytic amount p-toluensulfonate acid. After 30 minutes the reaction mixture was cooled to room temperature and distributed between ethyl acetate and saturated sodium bicarbonate solution. The phases were separated and the organic portion was dried over anhydrous Na2SO4, filtered and evaporated, thus obtaining the raw (untreated) product. When cleaning chromatography with reversed phase received 0,094 g (70%) indicated in the title compound in the form of a solid white color: TPL 64-66°C;1H NMR (CDCl3) δ to 7.93 (d, J=2.7 Hz, 1H), 7,47-7,40 (m, 2H), 7,37-7,29 (m, 5H), 7,08-7,00 (m, 2H), 5,81-5,70 (SIRM, 1H), from 5.29 (s, 2H), 5,12 (d, J=6,9 Hz, 2H), 4,63 (s, 2H); MS (ESI)m/z358 (M+H)+.

Obtaining complex [5-fluoro-2-(4-forbindelse)pyrimidine-4 - ylamino]methyl ester 2,2-dimethylpropionic acid (19):

To a mixture of [5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamino]methanol (0.10 g, of 0.37 mmol) in pyridine (2 ml) was added trimethylacetylchloride (0,048 g, 0.40 mmol) and the mixture was stirred on an orbital shaker at 60°C for 4 hours. The reaction mixture was cooled, evaporated to dryness and was distributed between EtOAc and water. The organic layer was dried over Na2SO4, filtered and evaporated, thus obtaining specified in the header connection (0,078 g, yield 60%) as a solid white color: TPL 134-135°C;1H NMR (300 MHz, CDCl3) δ of 7.97 (d, J2,5 Hz, 1H), 7,49-7,44 (m, 2H), 7,11-7,03 (m, 2H), 6,17 (shirt, J=7 Hz, 1H), 6,17 (d, J=7,4 Hz, 2H), 5,33 (s, 2H), 1,20 (s, 9H); HPLC-MSm/z352 (M+H)+.

GettingN'-[5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]-N,Ndimethylformamidine (20):

To a solution of 5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamine (1,00 g, 4.2 mmol) inN,Ndimethylformamide (DMF, 20 ml) under stirring with a magnetic stirrer was addedN,N-dimethylformamidine (0.55 g, 4.6 mmol) and continued stirring for 16 hours at room temperature. The solution was poured into 100 ml ice water, and then received a white precipitate. The mixture was cooled at 0°C for 1 hour and then filtered, thus obtaining specified in the title compound (1.10 g, 89%) as a solid white color: TPL 113-115°C;1H NMR (CDCl3) δ 8,65 (s, 1H), 8,04 (d, J=2.6 Hz, 1H), 7,46-7,40 (m, 2H), 7,07-6,98 (m, 2H), and 5.30 (s, 2H), 3,17 (s, 3H), and 3.16 (s, 3H); MS (ESI)m/z292 (M+H)+.

Theoretically calculated for C14H14F2N4O: C - 57,53; H OF 4.83; N - 19,17. Found: C - 57,67; H - 4,84; N - KZT 19.09.

Obtain [5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]-[1-pyrrolidin-1-iletiler]amine (21):

To a solution of N'-[5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]-N,N-dimethylformamidine (0.10 g, 0.36 mmol) in toluene (2 ml) was added pyrrolidine (0,051 g to 0.72 mmol) and catalytic amount of camp Sultonova acid. The tube vent tube was placed on an orbital shaker, was stirred at 90°C for 16 hours, cooled and the content was evaporated to dryness. When cleaning chromatography with reversed phase has been specified in the header connection (to 0.060 g, yield 53%) as a solid white color: TPL 102-103°C;1H NMR (300 MHz, CDCl3) δ 8,87 (s, 1H), of 8.06 (d, J=2.7 Hz, 1H), 7,49-7,42 (m, 2H), 7,09-7,01 (m, 2H), 5,32 (s, 2H), of 3.73-3,62 (m, 4H), 2,07 is 1.96 (m, 4H); HPLC-MS (ESI)m/z319 (M+H)+.

Obtaining N-[5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]-N'-hydroxytriazine (22):

To a solution of N'-[5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]-N,N-dimethylformamidine (0.10 g, 0.34 mmol) in EtOH (2 ml) was added hydroxylamine hydrochloride (0,047 g of 0.68 mmol)and the mixture was stirred on an orbital shaker for 1.5 hours at 50°C. the Reaction mixture was cooled and evaporated to dryness. Added water to obtain a suspension, which was filtered, while highlighting specified in the header connection (0,090 g, yield 94%) as a solid white color: TPL 169-171°C;1H NMR (300 MHz, CDCl3) δ of 8.15 (d, J=2.2 Hz, 1H), 8,02 (Sirs, 2H), 7,49-the 7.43 (m, 2H), 7,11-7,02 (m, 3H), to 5.35 (s, 2H); HPLC-MS (ESI)m/z281 (M+H)+, 279 (M-H)-.

Obtaining N-[5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]-N'-cyanoformate (23):

The cyanamide (8.00 g, 190,0 mmol who) was stirred while boiling under reflux in triethylorthoformate (60 ml) for 2 hours. The reaction mixture was cooled to room temperature and distilled, thus obtaining the ethyl-N-cyanoimino (12.5 g, so boiling = 110-112°C/45 mm Hg).* To the obtained imidate (1 ml) was added 5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamine (0.05 g, 0.2 mmol), the mixture was heated at 90°C for 4 hours, cooled, diluted with chloroform, filtered and evaporated. Raw (untreated) the product was purified by chromatography with reversed phase, while receiving 0,053 g (17%) indicated in the title compound in the form of solid substances not quite white: TPL 148-149°C;1H NMR (300 MHz, CDCl3) δ 9,45 and 9.33 (shirt, Sirs, J=10 Hz, 1H), 8,33 and of 8.25 (2D, J=2 Hz, 1H), 7,46-7,38 (m, 2H), 7,11-7,01 (m, 2H), 5.35 and 5,33 (2s, 2H); HPLC-MS (ESI)m/z290 (M+H)+, 288 (M-H)-.

* Bridsen Peter K. and Wang Xiaodong,Synthesis, 1995, 855-8.

Obtaining N'-[5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]-N,N-dimethylpropanamide (24):

To a solution ofN,N-dimethylpropanamide (0,202 g, 2.0 mmol) in CHCl3(2 ml) was added phosphorus oxychloride (POCl3; of 0.066 g, 0.43 mmol) and the mixture was stirred on an orbital shaker at room temperature for 1 hour. Was added triethylamine (0,22 g, 2.2 mmol) and 5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamine (0.10 g, 0.40 mmol) and stirred the mixture at 50°C for 3 hours, cooled to room temperature, was distributed between chloroform and water, the phase section is ranged and the organic portion was evaporated under reduced pressure. When cleaning chromatography with reversed phase has been specified in the header connection (0,042 g, yield 31%) as a yellow oil:1H NMR (300 MHz, CDCl3) δ 8,87 (s, 1H), 8,04 (d, J=2.5 Hz, 1H), 7,46-7,40 (m, 2H), 7,07-of 6.99 (m, 2H), and 5.30 (s, 2H), 3,13 (s, 6H), to 2.55 (q, J=7.7 Hz, 2H)and 1.15 (t, J=7.7 Hz, 3H); HPLC-MS (ESI)m/z321 (M+H)+.

Obtaining N'-(5-fluoro-2-hydroxypyrimidine-4-yl)-N,N-dimethylformamidine (25):

To a solution of 4-amino-5-ftorpirimidinu-2-ol* (4,00 g, was 31.0 mmol) in DMF (100 ml) under stirring with a magnetic stirrer was addedN,N-dimethylformamidine (4,00 g 34,0 mmol). The mixture was stirred at room temperature for 72 hours, diluted simple diethyl ether (200 ml) and filtered. The solid product was washed with heptane, while receiving specified in the header connection (5,23 g, yield 92%) as a solid white color: TPL 240-243°C;1H NMR (300 MHz, DMSO-d6) δ 10,7 (Sirs, 1H), 8,59 (s, 1H), 7.7 (d, J=5.6 Hz, 1H), 3,18 (s, 3H), 3,06 (s, 3H); HPLC-MS (ESI)m/z185 (M+H)+, 183 (M-H)-.

*4-amino-5-ftorpirimidinu-2-ol can be purchased on sale.

Obtaining complex 4-(dimethylaminomethylene)-5-ftorpirimidinu-2-Eletropaulo ester of carbonic acid (26):

To a solution of N'-(5-fluoro-2-hydroxypyrimidine-4-yl)-N,N-dimethylformamidine (0,10, 0.54 mmol) in CH2Cl2(2 ml) add the Yali the triethylamine (0.20 g, 2.0 mmol) and ethylchloride (0,065 g to 0.60 mmol) and the mixture was stirred on an orbital shaker at room temperature over night. The reaction mixture was diluted with CH2Cl2and the solution was washed with water, dried over MgSO4, was filtered and was evaporated. Raw (untreated) the product was purified column chromatography on silica gel (gradient EtOAc/petroleum ether), while receiving 0,031 g (22%) indicated in the title compound in the form of a solid white color: TPL 124-126°C;1H NMR (300 MHz, CDCl3) δ 8,67 (s, 1H), 8,19 (d, J=2.2 Hz, 1H), 4,35 (kV, J=7,14 Hz, 2H), 3,21 (s, 6H), of 1.40 (t, J=7,14 Hz, 3H); HPLC-MS (ESI)m/z258 (M+H)+.

Obtaining complex 4-(dimethylaminomethylene)-5-ftorpirimidinu-2-silt ester of benzoic acid (27):

To a suspension of N'-(5-fluoro-2-hydroxypyrimidine-4-yl)-N,N-dimethylformamidine (0.10 g, 0.54 mmol) in pyridine (2 ml) was added benzoyl chloride (0,084 g to 0.60 mmol) and the mixture was stirred on an orbital shaker for 16 hours at room temperature. The reaction mixture was distributed between EtOAc and saturated aqueous NaHCO3, the organic phase was dried over solid MgSO4, filtered and evaporated, thus obtaining specified in the header connection (0,147 g, 94%) as a solid white color: TPL 136-138°C;1H NMR (300 MHz, CDCl3) δ 8,69 (s, 1H), 8,27 (d, J=2.4 Hz, 2H),8,25-to 8.20 (m, 2H), 7,69-7,63 (m, 1H), 7,56-7,49 (m, 2H), 3,23 (s, 3H), 3,20 (s, 3H); HPLC-MS (ESI)m/z289 (M+H)+.

Obtaining complex 4-(dimethylaminomethylene)-5-ftorpirimidinu-2-silt ether of benzosulfimide acid (28):

To a suspension of N'-(5-fluoro-2-hydroxypyrimidine-4-yl)-N,N-dimethylformamidine (0.10 g, 0.54 mmol) in pyridine (2 ml) was added benzosulphochloride (0,106 g to 0.60 mmol) and the mixture was stirred on an orbital shaker for 16 hours at room temperature. The reaction mixture was distributed between EtOAc and saturated aqueous NaHCO3and the organic phase was dried over solid MgSO4, filtered and concentrated under reduced pressure. When cleaning chromatography with reversed phase gradient of H2O/MeCN) has been specified in the header connection (0,089 g, yield 46%) as a solid white color: TPL 124-125°C;1H NMR (300 MHz, CDCl3) δ 8,54 (s, 1H), 8,12-8,07 (m, 3H), 7,73-7,66 (m, 1H), 7,62-7,56 (m, 2H), 3,21 (s, 6H); HPLC-MS (ESI)m/z325 (M+H)+.

Obtaining complex 4-amino-5-ftorpirimidinu-2-silt ether of benzosulfimide acid (29):

To a solution of HCl in dioxane (3 ml of 10%aqueous solution) was added to complex 4-(dimethylaminomethylene)-5-ftorpirimidinu-2-silt ether of benzosulfimide acid (0,090, 0.3 mmol) and the mixture was stirred on an orbital shaker for PR the room temperature for 1.5 hours. The solvent was removed by evaporation, the residue was dissolved in a solution of dioxane and water (2.5 ml, 1:1) and was treated with saturated aqueous NaHCO3(0.5 ml). After 16 hours the reaction mixture was distributed between EtOAc and water, the organic phase was dried over Na2SO4was filtered and the solvent evaporated, thus obtaining specified in the header connection (0,059 g, yield 79%) as a solid white color: TPL 139-141°C;1H NMR (300 MHz, DMSO-d6)δ8,05-of 8.00 (m, 3H), of 7.90 to 7.75 (m, 3H), 7,70-7,63 (m, 2H); HPLC-MS (ESI)m/z268 (M-H)-, 270 (M+H)+.

Obtaining complex 4-amino-5-ftorpirimidinu-2-silt ether of benzosulfimide acid (29):

To a suspension of 5-fortitudine (0,177 g, 1.4 mmol) in pyridine (5 ml) was added benzosulphochloride (0,284 g, 1.6 mmol) and the mixture was stirred at room temperature for 2 hours. The reaction mixture was evaporated to dryness and the crude (crude substance was purified by chromatography with reversed phase, while receiving specified in the header connection (0,106 g, yield 29%) as a solid white color: TPL 145-146°C;1H NMR (300 MHz, DMSO-d6) δ8,05-of 8.00 (m, 3H), 7,9 to 7.75 (m, 3H), 7,70-7,63 (m, 2H); HPLC-MS (ESI) m/z 270 (M+H)+, 268 (M-H)-.

Receive (2-terbisil)-[5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]amine (30):

A) a solution of 2,4-dichloro-5-ftorpirimidinu* (0,105 g to 0.63 mmol) in 5 ml of dry THF was treated under stirring with a magnetic stirrer 2-tormentilline (of 0.085 g of 0.68 mmol) and excess triethylamine and the resulting mixture was heated at 80°C for 5 hours. The reaction mixture was distributed between CH2Cl2and diluted HCl, the organic phase is washed with saturated salt solution, dried over Na2SO4and filtered. The solvent was removed under reduced pressure, thus obtaining of) 0.157 g (97%) indicated in the title compound in the form of a solid yellow: TPL 117-118°C;1H NMR (300 MHz, CDCl3) δ of 7.90 (d, J=2,6, 1H), 7,47-7,27 (m, 2H), 7,21-7,01 (m, 2H), 5,54 (s, 1H), amounts to 4.76 (d, J=5,9, 2H); MS (ESI)m/z256 (M+H)+.

*2,4-dichloro-5-ftorpirimidinu can be purchased on sale.

B) a Solution of (2-chloro-5-ftorpirimidinu-4-yl)-(2-terbisil)amine* (0,103 g, 0.40 mmol) in 5 ml of dry THF was treated with 4-forbindelsen alcohol (0,062 g, 0.49 mmol) and 1.0 M solution of KO-t-Bu in t-BuOH (0.4 ml, 0.4 mmol). The mixture was heated at 80°C in hermetically sealed tube for 18 hours, distributed between CH2Cl2and water; the organic phase is washed with saturated salt solution, dried over Na2SO4and filtered. The solvent was removed under reduced pressure, the residue was purified column flash chromatography (SiO2, 10→20% EtOAc/petroleum ether), while receiving specified the title compound (of) 0.157 g, 42%) as a solid white color: TPL 83-84°C;1H NMR (300 MHz, CDCl3) δ 7,83 (d, J=2,8, 1H), 7,45-7,27 (m, 5H), 7,15-of 6.96 (m, 5H), lower than the 5.37 (Sirs, 1H), from 5.29 (s, 3H), 4,74 (d, J=5,9, 3H); MS (ESI)m/z346 (M+H)+.

*Singh, R.; Argade A.; D.G. Payan; Clough J.; Keim, H.; Sylvain C; Li, H.; Bhamidipati, S., patent application WO 2004014382 A1 20040219

Getting 5-fluoro-2-(3-methoxybenzyloxy)-4-(1-(4-methoxyphenyl)hydrazine)pyrimidine (31):

A) To a mixture of 2,4-dichloro-5-ftorpirimidinu (5,04 g, to 30.1 mmol) and 3-methoxybenzylamine alcohol (7.8 ml of 62.8 mmol) in a 250 ml round bottom flask was added a 1.0 M solution of KO-t-Bu in KO-t-Bu (66 ml, 66 mmol). There was a significant exothermic heat, the resulting mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with EtOAc (100 ml) and washed with saturated salt solution (50 ml × 2). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. Crystallization from hot EtOH was obtained substance was collected on a funnel with a porous filter and washed with EtOH, cooled with ice, while receiving specified in the header connection (7,94 g, 71%) as a solid white color: TPL 81-83°C;1H NMR (300 MHz, CDCl3) δ 8,10 (d, J=2.3 Hz, 1H), 7,29 (m, 2H), 7,02 (m, 4H), 6.87 in (dt, J=2,2, 7,8 Hz, 2H), 5,44 (s, 2H), to 5.35 (s, 2H), 3,82 (s, 3H), 3,82 (s, 3H); MS (ESI)m/z371 (M+H)+.

B) To a mixture of 5-fluoro-2,4-bis-(3-labels is benzyloxy)pyrimidine (7.9 g, of 21.3 mmol) and EtOH (21 ml) in a 500 ml round bottom flask was added 2,0N solution of KOH in water (85 ml, 170 mmol). Attach the reflux condenser and heated the reaction mixture at 95°C for 16 hours. After cooling to room temperature the reaction mixture was washed with Et2O (2×50 ml) and then acidified using 1N HCl solution to pH 3. The obtained solid substance was collected on a funnel with a porous filter. With subsequent extraction with excess EtOAC and concentration under reduced pressure has been specified in the header connection (3,63 g, 68%) as a solid white color: TPL 136-139;1H NMR (300 MHz, DMSO-d6) δ 12,97 (Sirs, 1H), 7,87 (d, J=3,7 Hz, 1H), 7,30 (t, J=7.9 Hz, 1H), 7,00 (m, 2H), 6,91 (DD, J=1,8, 8.0 Hz, 1H), from 5.29 (s, 2H), 3,74 (s, 3H); MS (ESI)m/z251 (M+H)+.

C) dried in a drying oven at 100 ml flask Slanka loaded 5-fluoro-2-(3-methoxybenzyloxy)pyrimidine-4-ol (3,63 g, 14.5 mmol) andN,N-dimethylaniline (3,7 ml, 29,2 ml). Was added phosphorus oxychloride (POCl3, 40 ml, 429 mmol) and the resulting solution was heated to 95°C in nitrogen atmosphere. After 2 hours the reaction mixture was cooled to room temperature and concentrated to constant volume under reduced pressure and 50°C. the Remaining residue was diluted in Et2O (50 ml) and washed with 1N HCl solution (2×50 ml). By concentration under reduced pressure were obtained solid substance was washed with water and with whom Bireli by filtration under vacuum. Specified in the title compound (4.09 g, 105%) were isolated in a solid white color: TPL 96-100°C;1H NMR (300 MHz, DMSO-d6) δ 8,81 (d, J=0.8 Hz, 1H), 7,30 (t, J=8,1 Hz, 1H), 7,02 (m, 2H), 6,91 (DD, J=2,3, 8,3 Hz, 1H), of 5.34 (s, 2H, in), 3.75 (s, 3H); MS (ESI)m/z269 (M+H)+.

D) To a mixture of 4-chloro-2-(3-methoxybenzyl)-5-ftorpirimidinu (0,153 g, 0,568 mmol) and hydrochloride of 4-methoxyphenylhydrazine (0,324 g of 1.85 mmol) in ethanol (5 ml) was added triethylamine (0,272, 2,69 mmol) and the mixture was heated to 50°C for 16 hours. The reaction mixture was cooled to room temperature and diluted with Et2O (50 ml). Et2O-the solution was washed with water (2×50 ml), dried over MgSO4, filtered and concentrated. The residue is triturated in Et2O, while receiving 5-fluoro-2-(3-methoxybenzyloxy)-4-(1-(4-methoxyphenyl)hydrazine)pyrimidine (0,113 g, yield 54%) as a solid white color: TPL 121-123,5°C;1H NMR (300 MHz, DMSO-d6) δ 8,02 (d, J=5.4 Hz, 1H), 7,28 (t, J=8,1 Hz, 1H), 7,22 (d, J=8.5 Hz, 2H), 6,99-6,93 (m, 2H), 6,93-6,85 (m, 3H), of 5.25 (s, 2H, in), 3.75 (s, 3H), 3,74 (s, 3H); MS (ESI)m/z371 (M+H)+, 354 (M-NH2)-.

Receiving O-allyl-N-(5-fluoro-2-(3-methoxybenzyloxy)pyrimidine-4-yl)hydroxylamine (32):

To a mixture of 4-chloro-2-(3-methoxybenzyl)-5-ftorpirimidinu (0,151 g, 0,558 mmol) and hydrochloride of O-arylhydroxylamine (0,201 g and 1.83 mmol) in a mixture of 5:1 MeOH:CH3CN (5 ml) was added triethylamine (0,273 g, 2,70 mm is l) and the mixture was heated at 50°C for 18 hours. The reaction mixture was cooled to room temperature and diluted with Et2O (50 ml). The organic solution was washed with water (2×50 ml), dried over MgSO4, filtered and concentrated. When cleaning flash chromatography (SiO2, 17%→50% EtOAc/hexane) receivedOallyl-N-(5-fluoro-2-(3-methoxybenzyloxy)pyrimidine-4-yl)hydroxylamine (0,113 g, yield 66%) as a colorless oil:1H NMR (300 MHz, DMSO-d6) δ 10,94 (broad singlet, 1H), 7,94 (broad singlet, 1H), 7,28 (t, J=8.0 Hz, 1H), 6,95-7,03 (m, 2H), to 6.88 (DD, J=2.5 and 7.9 Hz, 1H), 5,97 (TDD, J=5,8, 10,6, of 17.0 Hz, 1H), 5,32 (DD, J=1,5, to 17.4 Hz, 1H), 5,24 (s, 2H), 5,22 (DD, J=1,2, 10,6 Hz, 1H), 4,39 (d, J=6.0 Hz, 2H), 3,74 (s, 3H); MS (ESI)m/z306 (M+H)+, 304 (M-H)-.

Obtaining 1-[2-(3-cyanobenzyl)-5-ftorpirimidinu-4-yl]-3-(2-terbisil)urea (34):

To a mixture of 3-(4-amino-5-ftorpirimidinu-2-intoximeter)benzonitrile (0.075 g, 0.31 mmol) and 2-fermentalization (0,59 ml, 0.46 mmol) in dry DMF (1.5 ml) under stirring with a magnetic stirrer was added LiHMDS (a 1.0 M solution in THF, 0.31 in ml, 0.30 mmol). The tube was closed with a stopper and stirred the mixture at room temperature for 8 hours. Was added a saturated aqueous solution of NH4Cl (3 ml)and the mixture was stirred for 4 hours. The heterogeneous mixture was filtered, the solid washed with hot water, washed with E2O and then dried in vacuum, thus obtaining specified the title compound (0.075 g, 62%) as a solid white color: TPL 177-178°C;1H NMR (400 MHz, DMSO-d6) δ 10,04 (s, 1H), 8,90 (t, J=5.7 Hz, 1H), of 8.37 (d, J=2,8 Hz, 1H), 7,85 (Sirs, 1H), 7,80 (d, J=7.5 Hz, 1H), 7,74 (d, J=8.0 Hz, 1H), 7,60 (t, J=7.8 Hz, 1H), 7,42-7,38 (m, 1H), 7,35-7,29 (m, 1H), 7,20-7,14 (m, 2H), 5,33 (s, 2H), 4,49 (d, J=5.8 Hz, 2H); HPLC-MS (ESI)m/z396,3 (M+H)+, 394,3 (M-H)-.

Obtaining 1-[5-fluoro-2-(3-methoxybenzyloxy)pyrimidine-4-yl]-(3'-propellerblades)-3-propylacetic (36):

To a mixture of 5-fluoro-2-(3-methoxybenzyloxy)pyrimidine-4-ylamine (0.075 g, 0.30 mmol) and propositionthe (0,057 ml of 0.60 mmol) in dry DMF (1.5 ml) under stirring with a magnetic stirrer was added LiHMDS (a 1.0 M solution in THF, of 0.60 ml of 0.60 mmol). The tube was closed with a stopper and stirred the reaction mixture at room temperature for 8 hours. The solvent is evaporated under reduced pressure and the crude (crude substance was purified by chromatography with reversed phase, while receiving specified in the header connection (0,043 g, 10%) as a solid, yellowish-brown: TPL 75-78°C;1H NMR (400 MHz, DMSO-d6) δ 12,34 (s, 1H), 8,49 (s, 1H), 7,89 (s, 1H), 7,29 (t, J=7.8 Hz, 1H), 7,05-7,01 (m, 2H), 6.90 to (DD, J=6,9 Hz, J=2.5 Hz, 1H), and 5.30 (s, 2H, in), 3.75 (s, 3H), 3,74-3,68 (m, 2H), 3,15-3,10 (m, 2H), 1,58-of 1.44 (m, 4H), 0,89-0,85 (m, 6H); HPLC-MS (ESI)m/z420,4 (M+H)+, 418,4 (M-H)-.

Obtaining 1-[2-(3-cyanobenzyl)-5-ftorpirimidinu-4-yl]-3-propylthiophene (37):

To a mixture of 3-(4-amino-5-ftorpirimidinu-2-intoximeter)benzonitrile (0.075 g, 0.31 mmol) and propalestinian (0,047 ml, 0.46 mmol) in dry DMF (1.5 ml) under stirring with a magnetic stirrer was added LiHMDS (a 1.0 M solution in THF, at 0.31 ml, 0.31 mmol). The tube was closed with a stopper and stirred the reaction mixture for 8 hours. In a test tube was added a saturated aqueous solution of NH4Cl (3 ml) and the mixture was stirred for 4 hours. The heterogeneous mixture was filtered, the solid washed with hot water, washed with a mixture of hexanol and dried under vacuum, thus obtaining specified in the header of the connection (by 0.055 g, 52%) as a solid light yellow color: TPL 163-165°C;1H NMR (400 MHz, DMSO-d6) δ10,77 (s, 1H), 10,38 (s, 1H), of 8.47 (d, J=2.7 Hz, 1H), of 7.90 (s, 1H), 7,82 (d, J=7.5 Hz, 1H), 7,78 (d, J=8,1 Hz, 1H), 7.62mm (t, J=7.7 Hz, 1H), 5,42 (s, 2H), 3,55 (DD, J=12,4, 6,8 Hz, 2H), 1,65-to 1.59 (m, 2H), 0.95 to (t, J=7.5 Hz, 3H); HPLC-MS (ESI)m/z346,3 (M+H)+, 344,2 (M-H)-.

Obtaining N-[5-fluoro-2-(4-methylbenzylamino)pyrimidine-4-yl]methanesulfonamide (38):

To a solution of 5-fluoro-2-(4-methylbenzylamino)pyrimidine-4-ylamine (0,100 g, 0.43 mmol) in anhydrous THF (4 ml) at room temperature was added dropwise LiHMDS (1.07 ml of 1.0 M solution, 1.07 mmol) and stirred received the orange solution for 20 minutes. Added methanesulfonamide (to 0.108 g of 0.94 mmol) is a single portion and stirred muddy, light orange solution within 60 minutes. The reaction extinguished saturated salt solution (5 ml) and separated THF-phase. The aqueous phase was extracted with EtOAc (5 ml)and the combined organic part was dried over Na2SO4, filtered and concentrated to an orange retinoid balance. The residue was purified flash chromatography (SiO2, 0→100% EtOAc/hexane), while receiving 0,034 g (26%) indicated in the title compound in the form of a solid white color: TPL 145-148°C;1H NMR (400 MHz, CDCl3) δ 8,19 (s, 1H), 7,33 (d, J=7.9 Hz, 2H), 7,17 (d, J=7.9 Hz, 2H), to 5.35 (s, 2H), 3,37 (s, 3H), of 2.35 (s, 3H); HPLC-MS (ESI)m/z312 (M+H)+, 310 (M-H)-.

Obtaining N-[5-fluoro-2-(4-forbindelse)pyrimidine-4-yl]-S-(2-nitrophenyl)digitoxigenin (39):

To a solution of 5-fluoro-2-(4-forbindelse)pyrimidine-4-ylamine (0.05 g, 0.2 mmol) and 1.0 M solution of KO-t-Bu intBuOH (1.0 ml, 1.0 mmol) was added nitrobenzenesulfonamide storage capacity (0.044 g, 0.23 mmol) in one portion and stirred obtained brown solution within 60 minutes. The reaction mixture was diluted with water (2 ml) and neutralized to pH 7 1N HCl solution. The aqueous phase was extracted with EtOAc (5 ml), the organic phases were combined, dried over Na2SO4, filtered and concentrated. Raw (untreated) substance was purified by chromatography with reversed phase, while receiving specified in the header is EDINENIE (0,020 g, 26%) as a solid yellow: TPL 184°C;1H NMR (300 MHz, CDCl3) δ at 8.36 (d, J=7,25 Hz, 1H), of 8.09 (d, J=2.3 Hz, 1H), to 7.59 (m, 1H), was 7.36 (m, 2H), 7,29 (m, 2H), to 6.88 (m, 2H), 6,23 (Sirs, 1H), 5,19 (s, 2H); HPLC-MS (ESI)m/z391 (M+H)+, 389 (M-H)-.

Obtaining complex 4-acetylamino-5-ftorpirimidinu-2-silt ether of benzosulfimide acid (40):

N-(5-fluoro-2-hydroxypyrimidine-4-yl)ndimethylacetamide* (200 mg, 1,17 mmol) suspended in pyridine (5 ml) and stirred at ambient temperature. To the suspension under stirring was added benzosulphochloride (226 mg, 1,29 mmol) and continued stirring for 16 hours. The solvent is evaporated in a stream of nitrogen and the residue suspended in dichloromethane (2-3 ml)were placed directly in a column with silica gel and was suirable the ethyl acetate in petroleum ether (gradient 0-50%), while highlighting 180 mg of 0.58 mmol (49%) indicated in the title compound in the form of a solid white color: TPL 142-143°C;1H NMR (DMSO-d6) δ 10,96 (s, 1H), 8,67 (d, J=2.6 Hz, 1H), 8,12-of 8.06 (m, 2H), 7,86-7,79 (m, 1H), 7,73-the 7.65 (m, 2H), 2,98 (s, 3H); HPLC-MS (ESI)m/z312 (M+H)+, 310 (M-H)-.

*N-(5-fluoro-2-hydroxypyrimidine-4-yl)ndimethylacetamide can be cooked known in the literature methods.

1. Duschinsky, R., Fells E., Hoffer M. U.S. patent 3309359

Obtaining complex 4-(dimethylaminomethylene)-5-ftorpirimidinu-2-roximation the ether of 2,2-dimethylpropionic acid ( 41):

N'-(5-fluoro-2-hydroxypyrimidine-4-yl)-N,N-dimethylformamide (100 mg, 0.54 mmol), cesium carbonate (196 mg, of 0.60 mmol) and chlorocyphidae (90 mg, 0.6 mmol) was stirred (shook) together in DMF (3 ml) at ambient temperature for 16 hours. The reaction mixture was distributed between ethyl acetate and water, dried over magnesium sulfate, filtered and evaporated, thus obtaining a colorless oil, which was treated with simple diethyl ether (3-4 ml), while receiving solid. The solid is removed, the ether solution was placed in a column with silica gel and was suirable the ethyl acetate in petroleum ether (gradient 0-50%), while highlighting 14 mg, 0.05 mmol (9%) specified in the connection header in the form of a solid white color: TPL 86-88°C;1H NMR (CDCl3) δ 8,73 (s, 1H), of 8.06 (d, J=2.6 Hz, 1H), 6,04 (s, 2H), 3,20 (s, 3H), 3,18 (s, 3H), of 1.16 (s, 9H); HPLC-MS (ESI)m/z299 (M+H)+.

Obtaining N'-(5-fluoro-2-methoxyethoxymethyl-4-yl)-N,N-dimethylformamidine (42):

N'-(5-fluoro-2-hydroxypyrimidine-4-yl)-N,N-dimethylformamide (100 mg, 0.54 mmol), cesium carbonate (196 mg, of 0.60 mmol) and simple bromatology ester (75 mg, 0.6 mmol) was stirred (shook) together in DMF (3 ml) at ambient temperature for 4 hours. The reaction mixture was distributed between ethyl acetate and the DOI, was dried over magnesium sulfate, filtered and evaporated, thus obtaining a colorless oil, which was placed directly in a column with silica gel and was suirable the ethyl acetate in petroleum ether (gradient 0-80%), while highlighting 23 mg, 0.1 mmol (19%) indicated in the title compounds as a colorless oil:1H NMR (CDCl3) δ 8,66 (s, 1H), with 8.05 (d, J=2.6 Hz, 1H), 5,46 (s, 2H), 3,53 (s, 3H), 3,17 (s, 3H), and 3.16 (s, 3H); HPLC-MS (ESI)m/z229 (M+H)+.

Obtain [5-fluoro-2-(3-methoxybenzyloxy)pyrimidine-4-yl]sulphonamide (43):

To a solution of 4-chloro-5-fluoro-2-(3-methoxybenzyloxy)pyrimidine* (1.3 g, 4,84 mmol) in dry DMF (5 ml) under stirring with a magnetic stirrer was added a premixed suspension of 60% NaH (0.45 g, 10,65 mmol) and sulphonamide (0,93 g, 9,68 mmol) in dry DMF (5 ml). The resulting suspension is not quite white was stirred at room temperature for 72 hours. Then, the resulting orange suspension was heated to 50°C for 48 hours and cooled to room temperature. The reaction mixture was distributed between ethyl acetate and a saturated solution of salt. The organic extract was dried over Na2SO4, was filtered and was evaporated. Raw (untreated) substance was purified column chromatography normal phase silica using gradient EtOAc/Hex and chromatography with reversed f is zoé using the gradient of H 2O/ACN, while receiving [5-fluoro-2-(3-methoxybenzyloxy)pyrimidine-4-yl]sulphonamide (115 mg, yield of 7.2%) as a solid white color: TPL 126-130°C;1H NMR (300 MHz, CD3OD) δ 8,01 (d, J=3,63 Hz, 1H), 7,25 (m, 1H), 7,01 (m, 2H), to 6.88 (m, 1H), lower than the 5.37 (s, 2H), of 3.78 (s, 3H); MS (ESI)m/z326,9 (M-H)-.

*intermediate product 4-chloro-5-fluoro-2-(3-methoxybenzyloxy)pyrimidine was obtained as described in synthesis31.

Getting 5-fluoro-4-hydrazine-2-(3-methoxybenzyloxy)pyrimidine (44):

In a 125 ml Erlenmeyer flask was loaded with 4-chloro-5-fluoro-2-(3-methoxybenzyloxy)pyrimidine (1.50 g, to 5.58 mmol) and EtOH (50 ml). Added hydrazine monohydrate (900 ml, 18.5 mmol) and left the resulting mixture was mixed at room temperature. After 22 hours the reaction mixture was transferred into a 500 ml Erlenmeyer flask and was diluted with water (200 ml), then from the solution to precipitate began to fall solid white. After stirring for 7 hours solid product was collected on a funnel with a porous filter and washed with excess water. After drying on a porous filter has been specified in the title compound (1.23 g, 83%) as a solid white color: TPL 103-106°C;1H NMR (300 MHz, DMSO-d6) δ 8,92 (Sirs, 1H), 7,86 (d, J=3.6 Hz, 1H), 7,27 (t, J=8,1 Hz, 1H), 6,94-7,01 (m, 2H), 6.87 in (DD, J=2,4, 7.9 Hz, 1H), 5,24 (s, 2H), 4,46 (Sirs, 2H), 3,74 (s, 3H); MS (ESI)m/z265,2 (M+H)+, 23,2(M-H) -.

Obtaining (E)-5-fluoro-2-(3-methoxybenzyloxy)-4-(2-(thiophene-2-ylmethylene)hydrazine)pyrimidine (45):

A 20 ml test tube was loaded 5-fluoro-4-hydrazine-2-(3-methoxybenzyloxy)pyrimidine (74,7 mg, 0,283 mmol), EtOH (2 ml), thiophene-2-carbaldehyde (26 μl, 0,284 mmol) and 1 M HCl in Et2O (14 μl, 0.014 mmol) and was heated at 50°C on a shaker. After 90 minutes the reaction mixture was cooled to room temperature, concentrated under high vacuum, thus obtaining specified in the header connection (77,8 mg, 77%) as a solid yellow: TPL 136-139°C;1H NMR (300 MHz, DMSO-d6) δ 11,46 (Sirs, 1H), 8,50 (Sirs, 1H), 8,16 (d, J=3.6 Hz, 1H), to 7.64 (d, J=5.0 Hz, 1H), 7,41 (d, J=3,4 Hz, 1H), 7,28 (t, J=8.0 Hz, 1H), 7,12 (DD, J=3,8, 4.8 Hz, 1H),? 7.04 baby mortality (m, 2H), to 6.88 (DD, J=2,4, 8,3 Hz, 1H), 5,27 (s, 2H), of 3.73 (s, 3H); MS (ESI) m/z 359,2 (M+H)+, 357,2 (M-H)-.

Getting 2-(benzyloxy)-4-[(dimethyl-λ4-sulfanilate)amino]-5-ftorpirimidinu (47):

In dried in a drying Cabinet 10 ml flask Slanka loaded 2-(benzyloxy)-5-ftorpirimidinu-4-amine (101 mg, 0,462 mmol), CH2Cl2(2 ml) and dimethyl sulfide (75,0 μl, of 1.02 mmol) and cooled to 0°C in an ice bath. AddedN-chlorosuccinimide (122 mg, 0,914 mmol) and left the resulting mixture was mixed at 0°C for 45 minutes and then at room temperature for 30 the minutes. Was added a solution of NaOMe in MeOH (25%solution, 360 μl, 1.35 mmol). After 20 minutes the reaction is extinguished with water (3 ml) and left to mix for 1 hour. Then the raw (untreated), the reaction mixture was diluted with CH2Cl2, washed with water (50 ml × 2), dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation, and then dried in a high vacuum, thus obtaining specified in the title compound (120 mg, 93%) as a solid substance not quite white: TPL 125-129°C;1H NMR (300 MHz, DMSO-d6): δ of 7.70 (d, J=3,9 Hz, 1H), 7,25-7,44 (m, 5H), to 5.21 (s, 2H), 2,75 (s, 6H); MS (ESI) m/z 281,1 (M+H)+.

*Yamamoto, Y.; Yamamoto, H.,J. Am. Chem. Soc. 2004, 126, 4128-4129.

Obtaining 1-[5-fluoro-2-(4-methylbenzylamino)pyrimidine-4-yl]-2,3-dipropyltryptamine (49):

To a solution of 1-[5-fluoro-2-(4-methylbenzylamino)pyrimidine-4-yl]-3-propylthiophene (0.50 g, of 1.40 mmol) in CH3CN (4 ml) was added potassium carbonate (0.20 g, of 1.40 mmol) at room temperature and under stirring with a magnetic stirrer and stirred the mixture for 20 minutes. At room temperature was addedN-propyl bromide (0,19 g of 1.40 mmol) and stirred the mixture for 15 hours. The reaction mixture was diluted with H2O and was extracted with CH2Cl2(3×20 ml). The combined organic layers were dried over Na2SO4that filter is the solvent evaporated. Raw (untreated) and the mixture was purified on silica (gradient EtOAc/hexane) was evaporated and the obtained fractions, while receiving 0,335 g (63%) of 1-[5-fluoro-2-(4-methylbenzylamino)pyrimidine-4-yl]-2,3-dipropyltryptamine in the form of a viscous liquid pale yellow:1H NMR (300 MHz, CDCl3) δ 10,56 (Sirs, 1H), of 8.09 (d, J=2.6 Hz, 1H), 7,31 (m, 2H), 7,24 (m, 2H), 5,28 (s, 2H), or 3.28 (DD, J=13,6, 6.5 Hz, 4H), of 2.36 (s, 3H), of 1.62 (m, 4H), 1,0 (t, J=7.4 Hz, 4H); HPLC-MS (ESI) m/z 377(M+H)+.

GettingO-(4-amino-5-ftorpirimidinu-2-yl)-tert-butyl-N-methyl-N-hydroxycarbonate (50):

In the test tube with screw cap volume 2 drachmas a solution of 4-amino-2-chloro-5-ftorpirimidinu (0.1 g, of 0.68 mmol) andtert-butyl-N-methyl-N-hydroxycarbonate* (0.11 g, 0.75 mmol) was treated with a 1.0 M solution of KO-tBu in t-BuOH (1.0 ml, 1.0 mmol) in one portion, the resulting yellow solution was heated at 100°C and was stirred for 24 hours. The reaction mixture was cooled, extracted with EtOAC (3×5 ml) and the solvent evaporated. Raw (untreated) and the mixture was purified by chromatography with reversed phase, while receiving 0.10 g (56,9%) specified in the connection header in a solid yellow color: TPL 123-125°C;1H NMR (300 MHz, CDCl3) δ of 7.96 (d, J=2.3 Hz, 1H), 5,26 (Sirs, 2H), 3,32 (s, 3H), USD 1.43 (s, 9H); MS (ESI)m/z259 (M+H)+.

*tert-butyl-N-methyl-N-hydroxy Ramat you can get well-known in the literature methods:

1. Carrasco M R,; R. Braun, T.; Serafimova I, M; Silva O,J. Org. Chem.,2003, 68 (1), 195.

Obtaining On-ethyl-5-fluoro-2-(4-forbindelse)pyrimidine-4-ylcarbamate (51):

5-fluoro-2-(4-forbindelse)pyrimidine-4-amine (300 mg, of 1.26 mmol) was stirred with chloroform (25 ml) and water (12 ml). Was added sodium bicarbonate (870 mg, 10,12 mmol) followed by the addition dropwise of thiophosgene (218 mg, 1.9 mmol). The reaction mixture was stirred at room temperature for 16 hours, then was diluted with chloroform (20 ml) and separated phases. The organic extract was dried over sodium sulfate, filtered and concentrated on a rotary evaporator to 1/3 volume. To the resulting solution of crude isothiocyanate in chloroform was added absolute ethanol (10 ml) and the mixture was heated in hermetically sealed tube for 1 hour. The reaction mixture was cooled to room temperature, concentrated and purified flash chromatography on silica, while receiving 45 mg (11%)Oethyl-5-fluoro-2-(4-forbindelse)pyrimidine-4-ylcarbamate in the form of a solid pale yellow color: TPL 109-119°C;1H NMR (CDCl3) δ 8,30 (Sirs, 2H), 7,44 (m, 2H), 7,06 (m, 2H), are 5.36 (s, 2H), 4,66 (kV, J=6 Hz, 2H), 1,45 (t, J=6Hz, 3H); HPLC-MS (ESI): m/z 326 (ES+).

GettingN-(5-fluoro-2-(4-forbindelse)pyrimidine-4-yl)attentioned (53):

N-(5-fluoro-2-(4-forbindelse)pyrimidine-4-yl)ndimethylacetamide (50 mg, 0.42 mmol) was mixed with 1,2-dichloroethane (3 ml) and reagent Lawesson (170 mg, 0.42 mmol) in a vessel for a microwave reactor Biotage Initiator®. The vessel was heated in a microwave reactor Biotage Initiator®to 100°C for 5 minutes, then cooled to room temperature, the contents of the vessel were filtered and diluted CH2Cl2. Then the reaction mixture was washed with saturated salt solution and the layers were separated. The organic extract was dried on silica and purified flash chromatography. The fractions containing the product was then evaporated to dryness and was purified again by HPLC with reversed phase, while receiving 4 mgN-(5-fluoro-2-(4-forbindelse)pyrimidine-4-yl)attentioned (4%) as a glassy substance yellow:1H NMR (CDCl3) δ 9,34 (width, 1H), 8,29 (d, J=3 Hz, 1H), 7,41 (m, 2H), 7,06 (m, 2H), 5,33 (s, 2H), 3,13 (s, 3H); HPLC-MS (ESI): m/z 294 (ES-).

Protocols for biological studies

1.Evaluation of fungicidal activity: leaf spot (mycosphaerella) wheat (Mycosphaerella graminicola; anamorph:Septoria tritici; Bayer code SEPTTR):

Wheat plants (variety Yuma) were grown from seeds in a greenhouse, in a mixture consisting of 50% mineralized soils Metro mix/50% soil without Metro to mix until fully appeared first sheet at 7-10 cuttings per pot. So the e plants were inoculable aqueous spore suspension of the fungus Septoria triticieither before treatment with fungicides or after it. After inoculation the plants kept at 100% relative humidity (one day in the dark in irrigated camera with the next two-three days in a lighted irrigated camera), allowing disputes to germinate and infect the leaf. Then the plants transferred to the greenhouse for disease development.

2.Evaluation of fungicidal activity: spot (Cercospora) sugar beet leaves (Cercospora beticola: Bayer code CERCBE):

Sugar beet (grade HH-88) were grown in soil without mixture Metro mix in the greenhouse. Spores were collected from the surface of the hydrated infected leaves by washing whole leaves in water and subsequent filtration through two layers of cheesecloth. Young seedlings were inoculable spore suspension. The plants were kept in the dark irrigated premises within 48 hours and then placed under a plastic cap in the greenhouse with a temperature of 26°C.

3.Evaluation of fungicidal activity: leaf spot (mycosphaerella) peanuts (Mycosphaerella arachidis; Bayer code MYCOAR; anamorph:Cercospora arachidicola):

The peanut seedlings (cultivar Star) were grown in soil without Metro mix. Spores were collected from the surface of the hydrated infected leaves by washing whole leaves in water and subsequent filtration through two layers of cheesecloth. Young seedlings were inoculable susp what SIA dispute. The plants were kept in the dark irrigated premises within 48 hours and then placed under a plastic cap in the greenhouse with a temperature of 26°C.

4.Evaluation of fungicidal activity: Apple scab (caused byVenturia inaequalis; Bayer code VENTIN):

Shoots of Apple trees (variety McIntosh or Golden Delicious) were grown in mixture Metro mix in the greenhouse. Fungus spores collected from tissues of infected leaves. Plants were inoculable spore suspension. Plants were placed in the irrigated environment with a relative humidity of 100% for 24 hours and then transferred into the greenhouse with a temperature of 18°C for the disease development.

5.Evaluation of fungicidal activity: black sigatoka of banana (caused byMycosphaerella fijiensis; Bayer code MYCOFI):

Effective against pathogenMycosphaerella fijiensistested on newly emerged leaves of banana plants grown in the field. 20 ml of the diluted composition of1the desired concentration was sprayed on each test sheet over the contoured area of 20×20 cm, Then the sheets were given the opportunity to become infected under natural inoculum and visually estimated the percentage of the disease by controlling later ~40-45 days.

The following table presents the activity of typical compounds according to the present invention, which were evaluated in the experiments described above. The efficiency is tested compounds for the successful control of the disease was determined by assessing the severity of the disease treated plants and the subsequent translation of the severity of the disease in the success rate of disease per level the spread of the disease among untreated inoculated plants.

In each case in tables I-III grading scale is as follows:

% of successful disease controlScore
76-100A
51-75B
26-50C
0-25D
not testedE

Table I
3 DC - 1 and DP-activity of compounds against SEPTTR at concentrations of 25 and 100 hours/million

Table II

1 DP-activity of compounds against SEPTTR at concentrations of 50 and 200ch./million

Table III

1 DP-activity of compounds against CERCBE, VENTIN and MYCOFI

1. The compound of the formula I

where R1represents-N(R3R4;
R2represents-OR21;
R3is:
H;
C1-C6-alkyl, optionally substituted by 1 to 3 groups of R5;
C2-C6alkenyl, optionally substituted by 1 to 3 groups of R5;
5 - or 6-membered heteroaromatic cycle selected from the group consisting of furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, triazolyl, with each heteroaromatic cycle optionally substituted by 1 to 3 groups of R29;
3H-isobenzofuran-1-IMT;
-C(=O)R6;
-C(=S)R6;
-C(=S)other8;
-C(=O)N(R8R10;
-OR7;
-P(O)(OR 15)2;
-S(O)2R8;
-SR8;
-Si(R8)3;
-N(R9R10;
-(CHR24)mOR29or
-C(=NR16)SR16;
where m is an integer from 1 to 3;
R4is:
H;
C1-C6-alkyl, optionally substituted by 1 to 3 groups of R5; or
-C(=O)R6;
alternatively, R3and R4taken together can form:
5 - or 6-membered saturated or unsaturated cycle containing 1-2 heteroatoms selected from N and O, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;
=C(R12)N(R13R14or
=C(R15OR15;
R5independently represents halogen, C1-C4-alkoxy, C1-C4-halogenoalkane, C1-C4-alkylthio, C1-C4-allogenicity, amino, C1-C3-alkylamino, C2-C6-alkoxycarbonyl, C2-C6-alkylsulphonyl, C2-C6-alkylaminocarbonyl, -OH, N-methylpiperazin;
R6independently represents H, C1-C6-alkyl, C2-C6-alkoxycarbonyl, C1-C4-alkoxyalkane, C2-C6-alkylaminocarbonyl; phenyl, phenoxy, where phenyl or phenoxy optionally can be substituted by 1 to 3 groups of R20A 5-membered unsaturated cycle containing 1-3 heteroatoms, where each cycle it is certainly may be substituted by 1 to 3 groups of R 11;
R7represents a C1-C6-alkyl, C2-C6alkenyl, benzyl which optionally may be substituted by 1-5 groups R20;
R8independently represents a C1-C6-alkyl, amino, C1-C6-alkylamino, C2-C6-dialkylamino, phenyl, optionally substituted by 1 to 3 groups of R29provided that R8is not C1-C6-alkyl when R21represents Si(R8)3;
R9represents H, C1-C6-alkyl, -C(=O)R17or phenyl, optionally substituted by 1 to 3 groups of R20;
R10represents H or C1-C6-alkyl or phenyl, optionally substituted by 1 to 3 groups of R20;
R11independently represents halogen, C1-C6-alkyl, C1-C6-alkoxy;
R12represents H;
R13and R14independently represent H, cyano, -HE, C1-C4-alkyl, C1-C6-alkoxy, phenyl or benzyl, where phenyl or benzyl optionally may be substituted by 1 to 3 groups of R20;
alternatively, R13and R14taken together can form:
5 - or 6-membered saturated cycle containing 1 heteroatom, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;
alternatively, R12and R3 taken together can form:
5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms, where each cycle may not necessarily be substituted by 1 to 3 groups of R11;
R15represents a C1-C6-alkyl;
R16represents H, C1-C6-alkyl or phenyl, optionally substituted by 1 to 3 groups of R20;
R17represents H, C1-C6-alkyl, C1-C6-alkoxy, phenyl, phenoxy, where each cycle may not necessarily be substituted by 1 to 3 groups of R20;
R18represents H, C1-C6-alkyl or C1-C6-halogenated;
R19represents H, C1-C6-alkyl, C1-C6-halogenated or benzyl;
R20independently represents halogen, cyano, nitro, amino, C1-C6-alkoxyalkane, C1-C6-alkyl, C1-C6-halogenated, C2-C6-alkoxyalkyl, C2-C6-halogenoacetyl, C1-C6-alkoxy, C1-C6-halogenoalkane, C1-C6-alkylthio, C1-C6-alkylamino, C2-C8-dialkylamino, C2-C6-alkoxycarbonyl, phenyl, benzyl, phenoxy or 5 - or 6-membered heteroaromatic cycle-containing N as the heteroatoms, where each phenyl, benzyl, phenoxy or 5 - or 6-membered heteroaromatic the cycle optionally may be substituted by 1-3 substituents, independently selected from the group R29;
R21is:
H, provided that R3and R4not equal to H;
C5-C14-alkyl;
C2-C4alkenyl;
C3-C4-quinil;
phenyl, naphthyl or tetrahydroquinoline, where each cycle is optionally substituted by 1 to 3 groups of R20;
-(CHR22)mR23;
-(CHR22)mC(O)OR24;
-(CHR22)mC(O)R25;
-(CHR22)mOR28;
-(CHR22)mSR28;
-(CHR22)mN(R26R27;
-C(=O)R25;
-N=C(R30)(R32);
-NR24C(=O)OR24;
-Si(R8)3;
-SO2R27;
C2-C6alkoxycarbonyl or
5 - or 6-membered heteroaromatic cycle selected from the group consisting of furanyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, thiazolyl, thiadiazolyl, oxazolyl, triazolyl or isoxazolyl, where each 5 - or 6-membered heteroaromatic cycle optionally may be substituted by 1-5 groups R20;
R22independently represents H, C1-C6-alkyl, benzyl or phenyl, where each of the benzyl or phenyl optionally may be substituted by 1 to 3 groups of R20;
R23is:
C1-C6-alkyl;
phenyl, optionally substituted by 1-5 groups R20;
heteroaromatic cycles condensed rings, selected from the group consisting of benzothiophene, chinoline, izochinolina, thieno[2,3-b]pyridyl, 1-methyl-1H-thieno[2,3-c]pyrazolyl, benzofuranyl and benzoimidazolyl, 2,3-dihydrobenzofuran-2-yl, 4-methyl-4H-thieno[3,2-b]pyrrol-5-yl, 1-methyl-1H-indol-5-yl, imidazo[1,2-a]pyridine-2-yl, imidazo[2,1-b]thiazol-6-yl, benzothiazol-2-yl, benzo[b]thiophene-7-yl and 1-methyl-1H-indazol-3-yl, where each cycle may be optionally substituted by 1 to 3 groups of R20;
naphthyl;
benzo[1,3]dioxole;
pyrrolidinone;
oxetanyl;
5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms selected from the group consisting of isothiazoline, oxadiazolyl, where each cycle may not necessarily be substituted by 1 to 3 groups of R11; or
5 - or 6-membered heteroaromatic cycle selected from the group consisting of furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, triazolyl, thiadiazolyl, oxazolyl, isoxazolyl, imidazolyl, thiazolyl,thiophene-2-yl and thiophene-3-yl, where each heteroaromatic cycle optionally may be substituted by 1 to 3 groups of R20;
R24represents H, C1-C6-alkyl, phenyl, where phenyl optionally may be substituted by 1 to 3 groups of R20;
R25is:
H;
C1-C6-alkyl;
phenyl, optionally substituted by 1 to 3 groups of R20; or
5-or 6-membered heteroaromatic cycle, selected from the group consisting of furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, thiazolyl, thiadiazolyl, oxazolyl, triazolyl and isoxazolyl;
R26and R27independently represent:
H;
C1-C6-alkyl;
phenyl, optionally substituted by 1 to 3 groups of R20; or
5 - or 6-membered saturated or unsaturated cycle containing 1 heteroatom selected from thiophenyl, where the cycle is optionally may be substituted by 1 to 3 groups of R11;
R28is:
C1-C6-alkyl;
phenyl, optionally substituted by 1 to 3 groups of R20;
R29independently represents halogen, cyano, nitro, C1-C6-alkyl, C1-C6-halogenated, C1-C6-hydroxyalkyl, C2-C6-alkoxyalkyl, C2-C6-halogenoacetyl, C2-C6alkenyl, C2-C6-halogenoalkanes, C3-C6-quinil, C3-C6-halogenoalkanes, hydroxyl, C1-C6-alkoxy, C1-C6-halogenoalkane, C2-C6-alkenylamine, C2-C6-halogenations, C3-C6-alkyloxy, C3-C6-halogenaryloxy, C1-C6-alkylthio, C1-C6-alkylsulfonyl, C1-C6-halogenallylacetic, C2-C6-alkanity, C2-C6-halogen is canisteo, C2-C6-halogenallylacetic, C3-C6-alkylthio, C3-C6-alkylsulfonyl, C3-C6-halogenallylacetic, C1-C6-alkylamino, C2-C8-dialkylamino, C3-C8-dialkylaminoalkyl, C3-C6-trialkylsilyl, thiazolyl, phenyl, pyrimidinyl or pyridyl, where thiazolyl, phenyl, pyridyl or pyrimidinyl optionally can be substituted by 1 to 3 groups of R20;
R30independently represents:
C1-C6-alkyl or phenyl, where the phenyl cycle optionally may be substituted by 1 to 3 groups of R20;
R32is:
C1-C6-alkyl or phenyl, where phenyl optionally may be substituted by 1 to 3 groups of R20.

2. The compound according to claim 1, in which:
R1represents-N(R3R4;
R2represents-OR21;
R3represents H;
R4represents H;
R8independently represents a C1-C6-alkyl, amino, C1-C6-alkylamino, C2-C6-dialkylamino, phenyl, optionally substituted by 1 to 3 groups of R29;
R11independently represents halogen, C1-C6-alkyl, C1-C6-alkoxy;
R20independently represents halogen, cyano, nitro, amino, C1-C6-alkoxyalkane, C -C6-alkyl, C1-C6-halogenated, C2-C6-alkoxyalkyl, C2-C6-halogenoacetyl, C1-C6-alkoxy, C1-C6-halogenoalkane, C1-C6-alkylthio, C1-C6-alkylamino, C2-C8-dialkylamino, C2-C6-alkoxycarbonyl, phenyl, benzyl, phenoxy or 5 - or 6-membered heteroaromatic cycle-containing N as the heteroatoms, where each phenyl, benzyl, phenoxy or 5 - or 6-membered heteroaromatic cycle optionally may be substituted by 1-3 substituents, independently selected from the group R31;
R21is:
H, provided that R3and R4not equal to H;
C5-C14-alkyl;
C2-C4alkenyl;
C3-C4-quinil;
phenyl, naphthyl or tetrahydroquinoline, where each cycle is optionally substituted by 1 to 3 groups of R20;
-(CHR22)mR23;
-(CHR22)mC(O)OR24;
-(CHR22)mC(O)R25;
-(CHR22)mOR28;
-(CHR22)mSR28;
-(CHR22)mN(R26R27;
-C(=O)R25;
-N=C(R30)(R32);
-NR24C(=O)OR24;
-Si(R8)3;
-SO2R27;
C2-C6alkoxycarbonyl or
5 - or 6-membered heteroaromatic cycle selected from the group consisting of furanyl, pyridine is La, pyrimidinyl, pyrazinyl, pyrazolyl, thiazolyl, thiadiazolyl, oxazolyl, triazolyl or isoxazolyl, where each 5 - or 6-membered heteroaromatic cycle optionally may be substituted by 1-5 groups R20;
R22represents H, C1-C6-alkyl, benzyl or phenyl, where each of the benzyl or phenyl optionally may be substituted by 1 to 3 groups of R20;
R23is:
C1-C6-alkyl;
phenyl, optionally substituted by 1-5 groups R20;
heteroaromatic cycles with condensed rings selected from the group consisting of benzothiophene, chinoline, izochinolina, thieno[2,3-b]pyridyl, 1-methyl-1H-thieno[2,3-c]pyrazolyl, benzofuranyl and benzoimidazolyl, 2,3-dihydrobenzofuran-2-yl, 4-methyl-4H-thieno[3,2-b]pyrrol-5-yl, 1-methyl-1H-indol-5-yl, imidazo[1,2-a]pyridine-2-yl, imidazo[2,1-b]the thiazole-6-yl, benzothiazol-2-yl, benzo[b]thiophene-7-yl and 1-methyl-1H-indazol-3-yl, where each cycle may be optionally substituted by 1 to 3 groups of R20;
naphthyl;
benzo[1,3]dioxole;
pyrrolidinone;
oxetanyl;
5 - or 6-membered saturated or unsaturated cycle containing 1-3 heteroatoms selected from the group consisting of isothiazoline, oxadiazolyl, where each cycle may not necessarily be substituted by 1 to 3 groups of R11; or
5 - or 6-membered heteroaromatic cycle, wybran the th group, consisting of furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, triazolyl, thiadiazolyl, oxazolyl, isoxazolyl, imidazolyl, thiazolyl, thiophene-2-yl and thiophene-3-yl, where each heteroaromatic cycle optionally may be substituted by 1 to 3 groups of R20;
R24represents H, C1-C6-alkyl, phenyl, where phenyl optionally may be substituted by 1 to 3 groups of R20;
R25is:
H;
C1-C6-alkyl;
phenyl, optionally substituted by 1 to 3 groups of R20; or
5 - or 6-membered heteroaromatic cycle selected from the group consisting of furanyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, thiazolyl, thiadiazolyl, oxazolyl, triazolyl and isoxazolyl;
R26and R27independently represent:
H;
C1-C6-alkyl;
phenyl, optionally substituted by 1 to 3 groups of R20; or
5 - or 6-membered saturated or unsaturated cycle containing 1 heteroatom selected from thiophenyl, where the cycle is optionally may be substituted by 1 to 3 groups of R11;
R28is:
C1-C6-alkyl or
phenyl, optionally substituted by 1 to 3 groups of R20;
R29independently represents halogen, cyano, nitro, C1-C6-alkyl, C1-C6-halogenated,1 -C6-hydroxyalkyl, C2-C6-alkoxyalkyl, C2-C6-halogenoacetyl, C2-C6alkenyl, C2-C6-halogenoalkanes, C3-C6-quinil, C3-C6-halogenoalkanes, hydroxyl, C1-C6-alkoxy, C1-C6-halogenoalkane,2-C6-alkenylamine, C2-C6-halogenations, C3-C6-alkyloxy, C3-C6-halogenaryloxy, C1-C6-alkylthio,1-C6-alkylsulfonyl, C1-C6-halogenallylacetic, C2-C6-alkanity,2-C6-halogenalkane, C2-C6-halogenallylacetic, C2-C6-alkylthio, C2-C6-alkylsulfonyl, C2-C6-halogenallylacetic, C1-C6-alkylamino, C2-C6-dialkylamino, C3-C6-dialkylaminoalkyl, C3-C6-trialkylsilyl, thiazolyl, phenyl, pyrimidinyl or pyridyl, where thiazolyl, phenyl, pyridyl or pyrimidinyl optionally can be substituted by 1 to 3 groups of R20;
R30independently represents:
C1-C6-alkyl or phenyl, where the phenyl cycle optionally may be substituted by 1 to 3 groups of R20;
R31represents a halogen With1-C6-alkyl or C1-C6-alkoxy; and
R32is the nd:
With1-C6-alkyl or phenyl, where the phenyl cycle optionally may be substituted by 1 to 3 groups of R20.

3. The compound according to claim 1, in which:
R1represents-N(R3R4;
R2represents-OR21;
R3represents H;
R4represents H;
R21represents: -(CHR22)mR23m is 1;
R22represents H;
R23is:
naphthyl;
benzo[1,3]dioxole or
phenyl, optionally substituted by 1-5 groups R20;
R20represents halogen, cyano, nitro, amino, C1-C6-alkoxyalkane,1-C6-alkyl, C1-C6-halogenated, C2-C6-alkoxyalkyl,2-C6-halogenoacetyl,1-C6-alkoxy, C1-C6-halogenoalkane, C1-C6-alkylthio,1-C6-alkylamino or phenoxy, where phenoxy optionally may be substituted by 1-3 substituents, independently selected from the group R31;
R31represents a halogen With1-C6-alkyl or C1-C6-alkoxy.

4. The compound according to claim 1, in which:
R1represents-N(R3R4;
R2represents-OR21;
R3represents H;
R4represents H;
R21represents: -(CHR 22)mR23m is 1;
R22represents N and
R23is:
phenyl, p-tolyl, 4-forfinal, 4-methoxyphenyl, 3-methoxyphenyl, thiophene-2-yl, thiophene-3-yl, 3-forfinal, 3-bromophenyl, benzothiophen-2-yl, 2,4,6-trimetilfenil, 1-ethyl-2-methoxyphenyl, 3-benzonitrile or 3-fluoro-4-methoxyphenyl.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of structural formula or a salt thereof, where each of Z1, Z2 and Z3 is independently selected from N and C(R9), where not more than one of Z1, Z2 and Z3 is N; each R9 is hydrogen; and is a second chemical bond between either W2 and C(R12), or W1 and C(R12); W1 is -N=, and W2(R14) is selected from -N(R14)- and -C(R14)=, such that when W1 is -N=, W2(R14) is -N(R14)- and is a second chemical bond between W1 and C(R12); R11 is selected from phenyl and a heterocycle which is selected from a saturated or aromatic 5-6-member monocyclic ring, which contains one or two or three heteroatoms selected from N, O and S, or an 8-member bicyclic ring which contains one or more heteroatoms selected from N, O and S, where R11 is optionally substituted with one or two substitutes independently selected from halogen, C1-C4 alkyl, =O, -O-R13, -(C1-C4 alkyl)-N(R13)(R13), -N(R13)(R13), where each R13 is independently selected from -C1-C4alkyl; or two R13 together with a nitrogen atom to which they are bonded form a 5-6-member saturated heterocycle, optionally containing an additional heteroatom selected from NH and O, where if R13 is an alkyl, the alkyl is optionally substituted with one or more substitutes selected from -OH, fluorine, and if two R13 together with the nitrogen atom to which they are bonded form a 5-6-member saturated heterocycle, the saturated heterocycle is optionally substituted on any carbon atom with fluorine; R12 is selected from phenyl, a 4-6-member monocyclic saturated ring and a heterocycle, which is selected from an aromatic 5-6-member monocyclic ring which contains one or two heteroatoms selected from N and S, where R12 is optionally substituted with one or more substitutes independently selected from halogen, -C≡N, C1-C4 alkyl, C1-C2 fluorine-substituted alkyl, -O-R13, -S(O)2-R13, -(C1-C4 alkyl)-N(R13)(R13), -N(R13)(R13); R14 is selected from hydrogen, C1-C4 alkyl, C1-C4 fluorine-substituted alkyl, C1-C4 alkyl-N(R13)(R13), C1-C4 alkyl-C(O)-N(R13)(R13); and X1 is selected from -NH-C(=O)-†, -C(=O)-NH-†, -NH-S(=O)2-†, where † denotes the point where X1 is bonded to R11. The invention also relates to a pharmaceutical composition having sirtuin modelling activity based on said compounds.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine to treat a subject suffering from or susceptible to insulin resistance, metabolic syndrome, diabetes or complications thereof.

18 cl, 2 tbl, 52 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of labelling paired helical filaments (PHF), which includes interaction of PHF with compound and detection of said compound presence, where compound has formula , in which -R- stands for , -Q- is selected from: -NHC(O)-, -N=N-, -CH=CH-; -P is selected from: ; -T is selected from: ; X represents N or CH; -W1-6, -G1-4, -P1-5 are such as given in the invention formula. Invention also relates to method of labelling aggregated tau-protein, which includes interaction of aggregated molecules of tau-protein with compounds and detection of said compound presence, and to compounds of formula , in which values of substituents are such as given in the invention formula.

EFFECT: formula compounds as labels of tau-protein and paired helical filaments (PHF).

28 cl, 5 dwg, 225 ex

FIELD: chemistry.

SUBSTANCE: invention relates to field of organic chemistry, namely to method of obtaining N-(1,5,3-dithiazonan-3-yl)amides of general formula (1): where R=p-C5H4N (a), (CH3)3CO (b), m-C5H4N (c), which consists in the following: hydrazides of general formula RC(O)NHNH2 (R=mentioned above) undergo interaction with 1,4-butanedithiol, preliminarily mixed at 20°C with water formaldehyde solution, in presence of catalyst crystallohydrate of copper chloride CuCl2·2H2O with molar ration 1,4-butanedithiol: CH2O : RC(O)NHNH2 : CuCl2·2H2O = 10:20:10:(0.3-0.7) at 75-85°C and atmospheric pressure for 44-52 h.

EFFECT: elaborated is method of obtaining novel compounds, which can be applied as biologically active compounds, selective sorbents and extractants of noble and precious metals.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry, namely to method of obtaining 3,3'-[methylenebis(1,4-phenylene)]-, 3,3'-[oxybis(1,4-phenylene)]- and 3,3'-(3,3'-dimethoxybiphenyl-4, 4'-diyl)-bis-1,5,3-dithiazepinanes of general formula (1): R=4-C6H4-CH2-C6H4-4/, 4-C6H4-O-C6H4-4/, 4-H3COC6H3-C6H3OCH3-4/ which consists in the following: arylamines [diaminodiphenylmethane, diaminodiphenyloxide, dimethoxybenzidine] undergo interaction with N-tert-butyl-1,5,3-dithiazepinane in presence of catalyst Sm(NO3)3·6H2O in argon atmosphere with molar ratio arylamine:N-tert-butyl-1,5,3-dithiazeoinane: Sm(NO3)3·6H2O = 10 : 20 : (0.3-0.7) at temperature ~20°C in system of solvents ethanol-chloroform for 2.5-3.5 h.

EFFECT: increased efficiency of applying compound as antibacterial, antifungal and antiviral agents, biologically active complexants, selective sorbents and extractants of precious metals, special reagents for suppressing bacterial vital activity in different technical media.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining 3,3'-[oxa(thia)alkane-α,ω-diyl]-bis-1,5,3-dithiazepinanes of general formula (1) R=CH2CH2OCH2CH2, (CH2CH2O)2CH2CH2, (CH2CH2S)2 , which consists in the following: oxa(thia)alkane-α,ω-diamine (3-oxapentane-1,5-diamine, 3,6-dioxaoctane-1,8-diamine, 3,4-dithiahexane-1,6-diamine) undergoes interaction with 1-oxa-3,6-dithiacycloheptane in ethanol-chloroform system of solvents in argon medium in presence of catalyst SmCl3·6H2O with molar ratio oxa(thia)alkane-α,ω-diamine: 1-oxa-3,6-dithiacycloheptane: SmCl3·6H2O = 10 : 20 : (0.3-0.7) at room (~20°C) temperature for 2.5-3.5 h.

EFFECT: elaborated is method of obtaining novel compounds which can be applied as selective sorbents and extractants of precious metals, preparations for protection of leather, fur, fabrics against biodamage, biologically active substances with respect to various microorganisms and sulfate-reducing bacteria.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to field of organic chemistry, namely, to method of obtaining N-(1,5,3-dithiazonan-3-yl)amides of general formula (1) where R=p-C5H4N (a), (CH3)3CO (b), m-C5H4N (c), which consists in the fact, that N1,N1,N8,N8-tetramethyl-2.7-dithiaoctane-1.8-diamine is subjected to interaction with hydrazide of general formula RC(O)NHNH2 [R=upper said] in presence of catalyst samarium nitrate crystalhydrate Sm(NO3)3·6H2O, at molar ratio N1,N1,N8,N8-tetramethyl-2.7-dithiaoctane-1.8-diamine: RC(O)NHNH2 : Sm(NO3)3·6H2O = 10 : 10 : (0.3-0.7) at temperature 75-85°C and atmospheric pressure in mixture of solvents ethyl alcohol-chloroform for 20-28 h.

EFFECT: method of obtaining novel compounds, which can be applied as biologically active compounds, selective sorbents and extractants of noble and precious metals, is developed.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula or , where Ar1 represents phenyl group, optionally substituted with one or several identical or non-identical halogen atoms; R1 represents hydrogen atom; R4, R5, R6a, R6b represent hydrogen atoms; Y, Z independently represent linear C1-4 alkylene group, optionally substituted with one linear C1-4 alkyl group; Ar2 stands for condensed with benzene 5-membered heterocyclic ring, containing one nitrogen atom and one sulphur atom, substituted with one linear C1-4 alkyl group, or derivative of 5- or 6-membered heterocyclic ring, containing one nitrogen atom and one sulphur atom, condensed with heteroaromatic 6-memebered ring, containing one or two nitrogen atoms, substituted with one linear C1-4 alkyl group, linear C1-4 alkoxygroup or group -NR7R8, where R7 and R8 independently stand for hydrogen atom, linear or branched C1-4 alkyl group, or R7 and R8 together with nitrogen atom form group of general formula , where R2, R3 represent linear C1-4 alkyl groups, A stands for group -CHR12, oxygen atom or group -NR9, where R12 and R9 stand for hydrogen atom or linear C1-4 alkyl group, m has value 1 or 2, n has value 1 or 2, o has value 0 or 1, p has value 0 or 1, Q stands for group -O-, group -N--H or group -N--CO-R10, where R10 stands for linear C1-4 alkyl group or -NH-R11 group, where R11 represents linear C1-4 alkyl group; and to their salts. Invention also relates to methods of obtaining therein and to based on them pharmaceutical composition, possessing antagonistic activity with respect to receptor CCR3.

EFFECT: obtained are novel compounds and based on them pharmaceutical compositions, which can be applied in medicine for obtaining medication, intended for treating asthma, allergic rhinitis, atopic dermatitis, eczema, inflammatory intestinal diseases, ulcerous colitis, Crohn's disease, allergic conjunctivitis, multiple sclerosis or HIV-infection and AIDS-associated diseases.

14 cl, 3 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a method of producing a salt of tetrazole methanesulphonic acid of formula (I) , which involves acylating a compound (II) with a compound (III) and then adding methanesulphonic acid. The invention also relates to an intermediate compound of formula (II) and a method for production thereof.

EFFECT: method according to the present invention can cut reaction time, improve safety and enables to obtain salts of tetrazole methanesulphonic acid of high purity with high output without using a column chromatography technique.

22 cl, 2 tbl, 3 ex

FIELD: biotechnologies.

SUBSTANCE: invention refers to a compound of formula (I):

,

where R1 represents NR7C(O)R8 or NR9R10; R2 represents hydrogen; R3 represents halogen; R4 represents hydrogen, halogen, cyano, hydroxy, C1-4alkyl, C1-4alkoxy, CF3, OCF3, C1-4alkylthio, S(O)(C1-4alkyl), S(O)2(C1-4alkyl), CO2H or CO2(C1-4alkyl); R5 represents C1-6alkyl (replaced with NR11R12 or heterocyclyl that represents nonaromatic 5-7-membered ring containing 1 or 2 heteroatoms independently chosen from a group containing nitrogen, oxygen or sulphur); R6 represents hydrogen, halogen, hydroxy, C1-4alkoxy, CO2H or C1-6alkyl (possibly replaced with NR15R16 group, morpholinyl or thiomorpholinyl); R7 represents hydrogen; R8 represents C3-6cycloalkyl (possibly replaced with NR24R25 group), phenyl or heteroaryl, which represents aromatic 5- or 6-membered ring containing 1 to 3 heteroatoms independently chosen from the group containing nitrogen, oxygen and sulphur, and which is probably condensed with one 6-membered aromatic or nonaromatic carbocyclic ring or with one 6-membered aromatic heterocyclic ring, where the above 6-membered aromatic heterocyclic ring includes 1 to 3 heteroatoms independently chosen from a group containing nitrogen, oxygen and sulphur; R9 represents hydrogen or C1-6alkyl (possibly replaced with pyrazolyl); R10 represents C1-6alkyl (possibly replaced with phenyl or heteroaryl group, which represents aromatic 5- or 6-membered ring containing 1 or 2 heteroatoms independently chosen from the group containing nitrogen, oxygen or sulphur, and which is possibly condensed with one 6-membered heterocyclic ring, where the above 6-membered aromatic heterocyclic ring contains 1 or 2 heteroatoms independently chosen from the group containing nitrogen, oxygen or sulphur; where the above phenyl and heteroaryl groups in R8, R9 and R10 are possibly independently replaced with the following group: halogen, hydroxy, C(O)R42, C1-6alkyl, C1-6hydroxyalkyl, C1-6halogenoalkyl, C1-6alkoxy(C1-6)alkyl or C3-10cycloalkyl; unless otherwise stated, heterocyclyl is possibly replaced with group of C1-6alkyl, (C1-6alkyl)OH, (C1-6alkyl)C(O)NR51R52 or pyrrolidinyl; R42 represents C1-6alkyl; R12, R15 and R25 independently represent C1-6alkyl (possibly replaced with hydroxy or NR55R56 group); R11, R16, R24, R51, R52, R55 and R56 independently represent hydrogen or C1-6alkyl; or to its pharmaceutically acceptable salts.

EFFECT: new compounds are obtained, which can be used in medicine for treatment of PDE4-mediated disease state.

10 cl, 2 tbl, 202 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to compounds of formula or a pharmaceutically acceptable salt of such a compound, where - X is a carbon atom and R1a and R2a together form a bond; or - X is a carbon atom, R1a and R2a together form a bond, and R1 and R2 together form a moiety , where the asterisk shows the bonding site of R2; or - X is a carbon atom, R1a is hydrogen or (C1-4)alkoxy, and R2a is hydrogen; and R1 and R2, unless indicated otherwise, independently denote hydrogen; (C1-5)alkyl; aryl, where aryl denotes naphthyl or phenyl, where said aryl is unsubstituted or independently mono- or disubstituted, where the substitutes are independently selected from a group consisting of (C1-4)alkyl, (C1-4) alkoxy and halogen; or heteroaryl, selected from pyridyl, thienyl, oxazolyl or thiazolyl, where said heteroaryl is unsubstituted; under the condition that if R2 is aryl or heteroaryl, R1 cannot be aryl or heteroaryl, where the aryl and heteroaryl are independently unsubstituted or substituted as defined above; R3 is hydrogen or -CO-R31; R31 is (C1-5)alkyl, (C1-3)fluoroalkyl or (C3-6)cycloalkyl; n equals 1, 2, 3 or 4; B is a -(CH2)m- group, where m equals an integer from 1 to 3; A is-(CH2)P-, where p equals 2 or 3; R4 is (C1-5)alkyl; W is , where R5 is hydrogen or (C1-5)alkyl; R8, R9 and R10 is independently hydrogen, halogen, (C1-5)alkyl, hydroxy, -(C1-5)alkoxy, -O-CO-(C1-5)alkyl, (C1-3)fluoroalkyl, (C1-3)fluoroalkoxy, -CO-(C1-5)alkoxy, (C1-2)alkoxy-(C1-4)alkoxy or -NH-CO-(C1-5)alkyl. The invention also relates to a pharmaceutical composition based on a compound of formula (I).

EFFECT: novel compounds which are useful as calcium channel blockers are obtained.

11 cl, 2 tbl, 166 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of structural formula or a salt thereof, where each of Z1, Z2 and Z3 is independently selected from N and C(R9), where not more than one of Z1, Z2 and Z3 is N; each R9 is hydrogen; and is a second chemical bond between either W2 and C(R12), or W1 and C(R12); W1 is -N=, and W2(R14) is selected from -N(R14)- and -C(R14)=, such that when W1 is -N=, W2(R14) is -N(R14)- and is a second chemical bond between W1 and C(R12); R11 is selected from phenyl and a heterocycle which is selected from a saturated or aromatic 5-6-member monocyclic ring, which contains one or two or three heteroatoms selected from N, O and S, or an 8-member bicyclic ring which contains one or more heteroatoms selected from N, O and S, where R11 is optionally substituted with one or two substitutes independently selected from halogen, C1-C4 alkyl, =O, -O-R13, -(C1-C4 alkyl)-N(R13)(R13), -N(R13)(R13), where each R13 is independently selected from -C1-C4alkyl; or two R13 together with a nitrogen atom to which they are bonded form a 5-6-member saturated heterocycle, optionally containing an additional heteroatom selected from NH and O, where if R13 is an alkyl, the alkyl is optionally substituted with one or more substitutes selected from -OH, fluorine, and if two R13 together with the nitrogen atom to which they are bonded form a 5-6-member saturated heterocycle, the saturated heterocycle is optionally substituted on any carbon atom with fluorine; R12 is selected from phenyl, a 4-6-member monocyclic saturated ring and a heterocycle, which is selected from an aromatic 5-6-member monocyclic ring which contains one or two heteroatoms selected from N and S, where R12 is optionally substituted with one or more substitutes independently selected from halogen, -C≡N, C1-C4 alkyl, C1-C2 fluorine-substituted alkyl, -O-R13, -S(O)2-R13, -(C1-C4 alkyl)-N(R13)(R13), -N(R13)(R13); R14 is selected from hydrogen, C1-C4 alkyl, C1-C4 fluorine-substituted alkyl, C1-C4 alkyl-N(R13)(R13), C1-C4 alkyl-C(O)-N(R13)(R13); and X1 is selected from -NH-C(=O)-†, -C(=O)-NH-†, -NH-S(=O)2-†, where † denotes the point where X1 is bonded to R11. The invention also relates to a pharmaceutical composition having sirtuin modelling activity based on said compounds.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine to treat a subject suffering from or susceptible to insulin resistance, metabolic syndrome, diabetes or complications thereof.

18 cl, 2 tbl, 52 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to using an oxadiazolyl compound of the formula I

,

wherein R1 and R2 mean hydrogen; X means a methylene group; Y represents an oxygen atom; n represents an integer of 0, 1, 2 or 3, and m represents an integer of 0 or 1; R3 means a group of N-oxide pyridine according to the formula B which is attached as shown by an unmarked bond: ,

wherein R4, R5, R6 and R7 are the same or different and mean hydrogen, lower alkyl, halogen, haloalkyl, trifluoromethyl; the term "alkyl" means carbon chains, unbranched or branched, containing one to six carbon atoms; the term "halogen" means fluorine, chlorine, bromine or iodine; or its pharmacologically acceptable salt for preparing a drug for preventing or treating diseases related to the central and peripheral nervous system, wherein the above drug is administered according to a dosage regimen characterised by a dosage rate within approximately twice a day to approximately once every two days.

EFFECT: optimising the dosage regimen.

84 cl, 3 dwg, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 5-membered heterocyclic compounds of general formula (I), their prodrugs or pharmaceutically acceptable salts, which possess xanthine oxidase inhibiting activity. In formula (I) T represents nitro, cyano or trifluoromethyl; J represents phenyl or heteroaryl ring, where heteroaryl represents 6-membered aromatic heterocyclic group, which has one heteroatom, selected from nitrogen, or 5-membered aromatic heterocyclic group, which has one heteroatom, selected from oxygen; Q represents carboxy, lower alkoxycarbonyl, carbomoyl or 5-tetrasolyl; X1 and X2 independently represent CR2 or N, on condition that both of X1 and X2 do not simultaneously represent N and, when two R2 are present, these R2 are not obligatorily similar or different from each other; R2 represents hydrogen atom or lower alkyl; Y represents hydrogen atom, hydroxy, amino, halogen atom, perfluoro(lower alkyl), lower alkyl, lower alkoxy, optionally substituted with lower alkoxy; nitro, (lower alkyl)carbonylamino or (lower alkyl) sulfonylamino; R1 represents perfluoro(lower alkyl), -AA, -A-D-L-M or -A-D-E-G-L-M (values AA, A, D, E, G, L, M are given in i.1 of the invention formula).

EFFECT: invention relates to xanthine oxidase inhibitor and pharmaceutical composition, which contain formula (I) compound.

27 cl, 94 tbl, 553 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 2-amino-5,5-difluoro-5,6-dihydro-4H-[1,3]oxazin-4-yl)-phenyl]-amide derivatives of formula I, having BACE1 and/or BACE2 inhibiting activity, pharmaceutical compositions based thereon and use thereof as therapeutically active substances. In general formula

,

R1 is selected from a group consisting of i) a 5-6-member heteroaryl containing 1-2 heteroatoms selected from nitrogen and oxygen, and ii) 5-6-member heteroaryl containing 1-2 heteroatoms selected from nitrogen and oxygen, substituted with 1-4 substitutes, individually selected from amide, cyano, cycloalkyl, cycloalkyl-lower alkynyl, cycloalkyl-lower alkyl, cycloalkyl-lower alkoxy, halogen atom, lower haloalkoxy, lower haloalkyl, lower alkyl and nitro; iii) lower alkyl; iv) lower alkyl substituted with 1-5 substitutes individually selected from a halogena tom and hydroxy; v) lower alkenyl substituted with furanyl; vi) cycloalkyl substituted with 1-4 substitutes individually selected from a halogen atom, lower haloalkyl; R2 is selected from a group consisting of i) hydrogen atom, ii) halogen atom, R3 is a lower alkyl; R4 is selected from a group consisting of i) a hydrogen atom, and ii) lower alkyl; R5 is selected from a group consisting of i) a hydrogen atom, and ii) lower alkyl; n equals 0, 1 or 2.

EFFECT: active compounds in the present invention are useful in therapeutic and/or preventive treatment, for example, of Alzheimer's disease and type 2 diabetes.

29 cl, 10 tbl, 83 ex

FIELD: chemistry.

SUBSTANCE: invention relates to application of compounds of formula I, where R1 represents hydrogen atom, C1-7-alkyl, C1-7-alkoxy, C1-7-alkyl, substituted with halogen atom, C1-7-alkoxy, substituted with halogen atom, halogen atom, cyano, nitro, hydroxy, C(O)O-C1-7-alkyl, S(O)2-C1-7-alkyl, C(O)OCH2-phenyl, OCH2-phenyl, tetrazol-1-yl, phenyl, possibly substituted with halogen atom, or represents phenyloxy, possibly substituted with halogen atom, or represents benzyl, possibly substituted with halogen atom, or represents benzyloxy, possibly substituted with halogen atom; in case, when n>1, R1 substituents can be similar or different; X represents -O-(CH2)2-, -O-CHR"-CH2-, -O-CH2-CHR', -O-CR"2-CH2-, -(CH2)2-CHR'-, -CHR'-(CH2)2-, -CR"2-(CH2)2-, -CH2-CHR'-CH2-, -CH2-CR"2-CH2-, -CHR"-O-CH2-, -CR"2-O-CH2-, -CF2(CH2)2-, -CR"2-CH2-, -SiR"2-(CH2)2-, -S-(CH2)2-, -S(O)2-(CH2)2-, -(CH2)4-, -CH2-O-(CH2)2-, formula (a) or (b), where m has value 0, 1, 2 or 3; R' represents C1-7-alkyl, C1-7-alkoxy or C1-7-alkyl, substituted with halogen atom; R" represents C1-7-alkyl or C1-7-alkyl, substituted with halogen atom; R2 represents hydrogen atom or C1-7-alkyl; Y represents phenyl, naphthyl, C3-6-cycloalkyl or pyridin-2- or 3-yl, pyrimidin-2-yl or quinolin-6 or 7-yl; n has value 1, 2 or 3; or pharmaceutically acceptable salt of acid attachment in manufacturing medication for treatment anxiety disorders, bipolar disorder, stress-induced disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson disease, neurodegenerative disorders, Alzheimer's disease, epilepsy and migraine. Invention also relates to compounds of formula I, where R1 represents hydrogen atom, C1-7-alkyl, C1-7-alkoxy, C1-7-alkyl, substituted with halogen atom, C1-7-alkoxy, substituted with halogen atom, halogen atom, cyano, nitro, hydroxy, C(O)O-C1-7-alkyl, S(O)2-C1-7-alkyl, C(O)OCH2-phenyl, OCH2phenyl, tetrazol-1-yl, phenyl, possibly substituted with halogen atom, or represents phenyloxy, possibly substituted with halogen atom, or represents benzyl, possibly substituted with halogen atom, or represents benzyloxy, possibly substituted with halogen atom; in case when n>1, R1 substituents can be similar or different; X represents -(CH2)2-CHR', -CHR'-(CH2)2-, -CR"2-(CH2)2-, -CH2-CHR'-CH2-, -CH2-CR"2-CH2-, -CF2(CH2)2-, formula (a), where m has value 0, 1, 2 or 3; R' represents C1-7-alkyl, C1-7-alkoxy or C1-7-alkyl, substituted with halogen atom; R" represents C1-7-alkyl or C1-7-alkyl, substituted with halogen atom; R2 represents hydrogen atom or C1-7-alkyl; Y represents phenyl, naphthyl, C3-6-cycloalkyl or pyridin-2- or 3-yl, pyrimidin-2-yl or chinolin-6 or 7-yl; n has value 1, 2 or 3; or pharmaceutically acceptable salt of acid attachment. Also claimed are methods of obtaining formula (I) compounds.

EFFECT: 4,5-dihydro-oxazol-2-ylamine derivatives for treatment of diseases, associated with biological function of receptors, associated with trace amines.

22 cl, 1 tbl, 176 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a 2,4-diamino-1,3,5-triazine derivative of general formula I, having protein kinase inhibitor properties, use thereof and a pharmaceutical composition based thereon. In general formula I Y is CH2, CHR', O, S, S(O) or S(O)2; X1, X2, X3 are independently selected from a CH groups or N; R1 is a C1-8 aliphatic group, C3-8 cycloalkyl, C6-10 aryl, ethylene-dioxyphenyl, methylene dioxyphenyl, pyridyl, each of which is optimally substituted with one or more identical or different groups R"; R' is hydrogen, OH, halogen, such as F, Cl, Br, I, or carboxyl or carboxamide, optimally N-substituted with (C1-6)alkyl, or cyano or halo(C1-8)alkyl, (C1-8)alkoxy, piperidinyl, optimally substituted with methyl; R" is R' or RD; R21, R22, R23, R24 are independently selected from groups F, Cl, Br, I, CN, (C1-16)alkyl; furthermore, R21 and R22 and/or R23 and R24 can be combined and represent one oxo (=O) group or together with a carbon atom can form a spirocycle containing 3 to 7 carbon atoms; furthermore, R21 and R24 together with two carbon atoms can form an aliphatic or aromatic ring containing 4 to 8 atoms, optionally substituted with one or more groups R'; RD is an oxo group =O or =S.

EFFECT: invention can be used to treat autoimmune or cancerous diseases, rheumatoid arthritis and non-Hodgkin lymphoma.

13 cl, 12 ex

FIELD: biotechnologies.

SUBSTANCE: invention refers to a compound of formula (I):

,

where R1 represents NR7C(O)R8 or NR9R10; R2 represents hydrogen; R3 represents halogen; R4 represents hydrogen, halogen, cyano, hydroxy, C1-4alkyl, C1-4alkoxy, CF3, OCF3, C1-4alkylthio, S(O)(C1-4alkyl), S(O)2(C1-4alkyl), CO2H or CO2(C1-4alkyl); R5 represents C1-6alkyl (replaced with NR11R12 or heterocyclyl that represents nonaromatic 5-7-membered ring containing 1 or 2 heteroatoms independently chosen from a group containing nitrogen, oxygen or sulphur); R6 represents hydrogen, halogen, hydroxy, C1-4alkoxy, CO2H or C1-6alkyl (possibly replaced with NR15R16 group, morpholinyl or thiomorpholinyl); R7 represents hydrogen; R8 represents C3-6cycloalkyl (possibly replaced with NR24R25 group), phenyl or heteroaryl, which represents aromatic 5- or 6-membered ring containing 1 to 3 heteroatoms independently chosen from the group containing nitrogen, oxygen and sulphur, and which is probably condensed with one 6-membered aromatic or nonaromatic carbocyclic ring or with one 6-membered aromatic heterocyclic ring, where the above 6-membered aromatic heterocyclic ring includes 1 to 3 heteroatoms independently chosen from a group containing nitrogen, oxygen and sulphur; R9 represents hydrogen or C1-6alkyl (possibly replaced with pyrazolyl); R10 represents C1-6alkyl (possibly replaced with phenyl or heteroaryl group, which represents aromatic 5- or 6-membered ring containing 1 or 2 heteroatoms independently chosen from the group containing nitrogen, oxygen or sulphur, and which is possibly condensed with one 6-membered heterocyclic ring, where the above 6-membered aromatic heterocyclic ring contains 1 or 2 heteroatoms independently chosen from the group containing nitrogen, oxygen or sulphur; where the above phenyl and heteroaryl groups in R8, R9 and R10 are possibly independently replaced with the following group: halogen, hydroxy, C(O)R42, C1-6alkyl, C1-6hydroxyalkyl, C1-6halogenoalkyl, C1-6alkoxy(C1-6)alkyl or C3-10cycloalkyl; unless otherwise stated, heterocyclyl is possibly replaced with group of C1-6alkyl, (C1-6alkyl)OH, (C1-6alkyl)C(O)NR51R52 or pyrrolidinyl; R42 represents C1-6alkyl; R12, R15 and R25 independently represent C1-6alkyl (possibly replaced with hydroxy or NR55R56 group); R11, R16, R24, R51, R52, R55 and R56 independently represent hydrogen or C1-6alkyl; or to its pharmaceutically acceptable salts.

EFFECT: new compounds are obtained, which can be used in medicine for treatment of PDE4-mediated disease state.

10 cl, 2 tbl, 202 ex

FIELD: chemistry.

SUBSTANCE: invention relates to arylpiperazine derivative of formula its pharmaceutically acceptable salts, as well as to its deuterated form, possessing affinity with respect to D2, 5-HT1A and 5-HT2A receptors.

EFFECT: compound can be used for treatment of schizophrenia and related psychotic disorders, such as acute maniacal disorder, bipolar disorder, autistic disorder and depression.

7 cl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel quinazoline derivatives of formula , where each of R1, R2 and R5, independently, represents H; one of R3 and R4 represents where n - 1 or 2; each Ra represents H, C1-10alkyl, optionally substituted with substituent, selected from group, including C1-10alkoxy, C1-10alkansulfonyl carboxy-group, 5-6-membered monocyclic heterocycloalkyl, which has one or several heteroatoms, selected from O and N, where N atom can be substituted with C1-10alkyl, phenyl, optionally substituted with halogen, 5-6-membered monocyclic heteroaryl, which has one or several heteroatoms, selected from N and S, 7-membered bicyclic heterocycloalkyl, which has 2 N atoms; C2-10alkenyl; C2-10alkinyl; cycloalkyl, representing saturated cyclic group, containing 3-6 carbon atoms; each of Rb and Rc, independently, represents H or C1-10alkyl, optionally substituted C1-10alkoxy, or Rb and Rc, together with atom of nitrogen, with which they are bound, form bicyclic ring of the following formula: , where each of m1, m2, m3, and m4 is 0, 1 or 2; A is CH; B is NR, where R is H or C1-10alkyl; and each of Ri, Rii, Riii, RiV, Rv, Rvi, Rvii and Rviii is H; or 6-7-membered monocyclic heterocycloalkyl, containing 1-2 N atoms, optionally substituted with substituent, selected from group, including hydroxy, C1-10alkyl, optionally substituted C1-10alkoxy, C1-10alkyl, optionally substituted with C3-6cycloalkyl; and each of Rd, Re, independently represents H, C2-10alkenyl; C2-10alkinyl; or C1-10alkyl, optionally substituted with substituent, selected from group, including C1-10alkyloxy, hydroxy, CN, 5-6-membered monocyclic heterocycloalkyl, which has 1 or 2 N atoms, optionally substituted with C1-10alkyl, halogen or 5-6-membered heterocycloalkyl, which has 1 N atom, phenyl, optionally substituted with halogen, cycloalkyl, representing saturated cyclic group, containing 3-6 carbon atoms, 5-6-membered monocyclic heteroaryl, which has one or 2 N atoms; or Rd and Re, together with nitrogen atom, with which they are bound, form 5-6-membered saturated heterocycloalkyl, which has 1-2 heteroatoms, selected from N and O, optionally substituted with substituent, selected from group, including C1-10alkyl (which is optionally substituted with C3-6cicloalkyl, C1-10alkoxy, halogen), 5-membered heterocycloalkyl, which has one N atom, halogen, C1-10alkansulfonyl, C1-10alkylcarbonyl, optionally substituted with halogen, or Rd and Re, together with nitrogen, with which they are bound, form 7-10-membered, saturated, bicyclic heterocycloalkyl, containing 1-2 heteroatoms, selected from N and O, optionally substituted with C1-10alkyl; and the other of R3 and R4 represents H, halogen or C1-10alkoxy; X represents NRf, where Rf represents phenyl, substituted with C2-4 alkinyl; and Z represents N. Invention also relates to particular quinazoline derivatives, based on it pharmaceutical composition, and to method of cancer treatment.

EFFECT: novel quinazoline derivatives, inhibiting EGFR activity are obtained.

11 cl, 171 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to compounds of formula or a pharmaceutically acceptable salt of such a compound, where - X is a carbon atom and R1a and R2a together form a bond; or - X is a carbon atom, R1a and R2a together form a bond, and R1 and R2 together form a moiety , where the asterisk shows the bonding site of R2; or - X is a carbon atom, R1a is hydrogen or (C1-4)alkoxy, and R2a is hydrogen; and R1 and R2, unless indicated otherwise, independently denote hydrogen; (C1-5)alkyl; aryl, where aryl denotes naphthyl or phenyl, where said aryl is unsubstituted or independently mono- or disubstituted, where the substitutes are independently selected from a group consisting of (C1-4)alkyl, (C1-4) alkoxy and halogen; or heteroaryl, selected from pyridyl, thienyl, oxazolyl or thiazolyl, where said heteroaryl is unsubstituted; under the condition that if R2 is aryl or heteroaryl, R1 cannot be aryl or heteroaryl, where the aryl and heteroaryl are independently unsubstituted or substituted as defined above; R3 is hydrogen or -CO-R31; R31 is (C1-5)alkyl, (C1-3)fluoroalkyl or (C3-6)cycloalkyl; n equals 1, 2, 3 or 4; B is a -(CH2)m- group, where m equals an integer from 1 to 3; A is-(CH2)P-, where p equals 2 or 3; R4 is (C1-5)alkyl; W is , where R5 is hydrogen or (C1-5)alkyl; R8, R9 and R10 is independently hydrogen, halogen, (C1-5)alkyl, hydroxy, -(C1-5)alkoxy, -O-CO-(C1-5)alkyl, (C1-3)fluoroalkyl, (C1-3)fluoroalkoxy, -CO-(C1-5)alkoxy, (C1-2)alkoxy-(C1-4)alkoxy or -NH-CO-(C1-5)alkyl. The invention also relates to a pharmaceutical composition based on a compound of formula (I).

EFFECT: novel compounds which are useful as calcium channel blockers are obtained.

11 cl, 2 tbl, 166 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 5-membered heterocyclic compounds of general formula (I), their prodrugs or pharmaceutically acceptable salts, which possess xanthine oxidase inhibiting activity. In formula (I) T represents nitro, cyano or trifluoromethyl; J represents phenyl or heteroaryl ring, where heteroaryl represents 6-membered aromatic heterocyclic group, which has one heteroatom, selected from nitrogen, or 5-membered aromatic heterocyclic group, which has one heteroatom, selected from oxygen; Q represents carboxy, lower alkoxycarbonyl, carbomoyl or 5-tetrasolyl; X1 and X2 independently represent CR2 or N, on condition that both of X1 and X2 do not simultaneously represent N and, when two R2 are present, these R2 are not obligatorily similar or different from each other; R2 represents hydrogen atom or lower alkyl; Y represents hydrogen atom, hydroxy, amino, halogen atom, perfluoro(lower alkyl), lower alkyl, lower alkoxy, optionally substituted with lower alkoxy; nitro, (lower alkyl)carbonylamino or (lower alkyl) sulfonylamino; R1 represents perfluoro(lower alkyl), -AA, -A-D-L-M or -A-D-E-G-L-M (values AA, A, D, E, G, L, M are given in i.1 of the invention formula).

EFFECT: invention relates to xanthine oxidase inhibitor and pharmaceutical composition, which contain formula (I) compound.

27 cl, 94 tbl, 553 ex

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