Malononitrile compound as pesticide


FIELD: chemistry.

SUBSTANCE: present invention pertains to a malononitrile compound with formula (I): where one of X1, X2, X3 and X4 stands for CR100, where R100 is a group with formula (II) each three of the other X1, X2, X3 and X4 is nitrogen or CR5, under the condition that, from one to three of X1, X2, X3 and X4 stands for nitrogen, Z is oxygen, sulphur or NR6. The malononitrile compound can be used a pesticide in agriculture.

EFFECT: obtaining a new pest control compound and its use as an active ingredient of a pesticide composition.

18 cl, 180 ex

 

The technical field

The present invention relates to the connection of malononitrile and its application.

The level of technology

For pest control agriculture developed and implemented in practice compounds with efficacy for control of pests of agriculture.

Description of the invention

The purpose of this invention is to provide compounds with excellent regulatory action against pests of agriculture, the pesticide composition comprising the compound as an active ingredient, and a method of combating agricultural pests using this connection.

The present invention relates to the connection of malononitrile represented by the formula (I):

where any of X1X2X3and X4represents CR100,

(where R100represents a group represented by the formula:

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally samisen the second one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens),

each of the other three of the X1X2X3and X4represents nitrogen or CR5provided that from one to three of the X1X2X3and X4represents nitrogen,

Z represents oxygen, sulfur or NR6,

R5independently represents halogen, cyano, nitro, hydroxyl, mercapto, formyl, SF5carboxyl, C1-C5 alkyl, optionally substituted by one or bore alkemi halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl optionally substituted by halogen or by one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, C2-C5 alkoxycarbonyl, optionally substituted by one or more halogen, a group represented NR10R11, a group represented by C(=X5)NR12R13, a group represented by (CH2)mQ, a group represented by C(=NOR17R18, a group represented by C(OR19R20R21or hydrogen,

R6represents a C1-C5 alkyl, long is Ino substituted by one or more halogen, C3-C5 of alkenyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, (C1-C5 alkoxy, optionally substituted by one or more halogen)C1-C3 alkyl, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, C2-C5 alkoxycarbonyl, optionally substituted by one or more halogen, a group represented by C(=X5)NR12R13, a group represented by (CH2)mQ, or hydrogen, and

when two CR5or CR5and NR6are located adjacent to each other, they can together represent a C2-C6 alcander or C4-C6 alcander, optionally substituted by one or more halogen, in which at least one methylene group forming alcander or alkerdeel may be replaced by oxygen, sulfur or NR7,

R7represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 of alkenyl, optionally substituted by one or more halogen, C3-C5 quinil not necessarily replaced by the ne or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, C2-C5 alkoxycarbonyl, optionally substituted by one or more halogen, or hydrogen,

each of R10and R11represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 of alkenyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, (C1-C5 alkoxy, optionally substituted by one or more halogen)C1-C3 alkyl, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, C2-C5 alkoxycarbonyl, optionally substituted by one or more halogen, or hydrogen,

or a group represented NR10R11is a 1-pyrrolyl,

each of R12and R13represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 of alkenyl, optionally substituted by one or more halogen, C3-C5 quinil, long is correctly substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, a group represented by (CH2)mQ, or hydrogen,

or R12and R13together represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

each of R17and R18represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 of alkenyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, a group represented by (CH2)mQ, or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 of alkenyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, (C1-C5 alkoxy, optionally substituted by one or more halogen)C1-C3 alkyl, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C alkylsulphonyl, optionally substituted by one or more halogen, C2-C5 alkoxycarbonyl, optionally substituted by one or more halogen, a group represented by C(=X5)NR12R13, a group represented by (CH2)mQ trialkylsilyl, or hydrogen,

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, or hydrogen,

Q represents aryl, optionally substituted R14n times,

R14independently represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by the ne or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, C2-C5 alkoxycarbonyl, optionally substituted by one or more Halogens, or halogen,

each of m and n is an integer from 0 to 5, and

X5represents oxygen or sulfur (hereinafter referred to in this invention as the present compound); pesticide composition comprising an effective amount of the present compound and an inert carrier, and to a method of combating agricultural pests, comprising applying an effective amount of the present compounds on the specified pest or a habitat of a specified pest.

The method of carrying out the invention

In the present invention "alcander" represents a chain saturated hydrocarbon group in which two different constituent carbon atom have a free valence. "Alcander" represents a chain saturated hydrocarbon group having one or two double bonds, in which two different constituent carbon atom have a free valence.

In the present invention "foralkyl" represents alkyl substituted by one or more fluorine atoms. Designation in the description of C1-C6, or the like means the total number of carbon atoms constituting the Deputy.

Currently the m invention, examples C1-C5 alkyl, optionally substituted by one or more halogen represented by R1or R2include C1-C3 alkyl, optionally substituted by one or more halogen, in particular methyl, ethyl, propyl, 1-methylethyl, 2,2-dimethylpropyl, chloromethyl, vermeil, deformity, trifluoromethyl, 2,2,2-triptorelin and 1,1,2,2-tetraborate; and 1,1-dimethylethyl.

Examples of C2-C5 alkenyl, optionally substituted by one or more halogen, include vinyl, 2,2-defermined, 1,2,2-tryptophanyl, 1-propenyl and 2-propenyl.

Examples of C2-C5 quinil, optionally substituted by one or more Halogens include ethinyl, 1-PROPYNYL, 2-PROPYNYL and 3,3,3-Cryptor-1-PROPYNYL.

Examples of C1-C5 alkoxy, optionally substituted by one or more halogen represented by R2include C1-C3 alkyl, optionally substituted by one or more Halogens, such as methoxy, ethoxy, 1 methylethoxy, formatosi, deformedarse, triptoreline, 2,2,2-triptoreline and 1,1,2,2-tetrafluoroethoxy; and butoxy.

Examples of C1-C5 alkyl, optionally substituted by one or more halogen represented by R3or R4include methyl, ethyl, 1-methylethyl, 2-methylpropyl, propyl, butyl, 3-methylbutyl, 2,2-dimethylpropyl, vermeil, chloromethyl, 2,2-dottorati, 2,2-dichloroethyl, 3,3-direcror, 3,3-dichloropropyl, trifluoromethyl, trichloromethyl, ,2.2-triptorelin, 2,2,2-trichloroethyl, 3,3,3-cryptochromes, 3,3,3-trichloropropane, 2,2-direcror, 3,3-deformaty, 1-bromo-2,2,2-triptorelin, 1-chloro-2,2,2-triptorelin, 1,2,2,2-tetraborates, pentafluoroethyl, 2,2,3,3,3-pentafluoropropyl, 1,1,2,2-tetraborate and 2,2,3,3-tetrafluoropropyl.

Examples of C2-C5 alkenyl, optionally substituted by one or more halogen, include vinyl, allyl, 1-propenyl, 3-butenyl, 2-methyl-1-propenyl, 3-methyl-2-butenyl, 3-pentenyl, 4-pentenyl, 3-methyl-3-butenyl, 4-methyl-3-pentenyl, 1-chloride, 2-chloride, 1-torvinen, 2-torvinen, 2,2-dichlorovinyl, 2,2-dibromovinyl, 2,2-defermined, 1,2,2-tryptophanyl, 1-(trifluoromethyl)vinyl, 2-chloro-2-propenyl, 3-chloro-2-propenyl, 2-fluoro-2-propenyl, 3-fluoro-2-propenyl, 3,3-dichloro-2-propenyl, 3,3-dibromo-2-propenyl, 3,3-debtor-2-propenyl, 2,3,3-Cryptor-2-propenyl, 2-(trifluoromethyl)-2-propenyl, 2,3,3,3-titrator-1-propenyl, 1,2,3,3,3-pendaftar-1-propenyl, 3,4,4-Cryptor-3-butenyl, 3,4,4,4-titrator-2-butenyl, 2,3,4,4,4-pendaftar-2-butenyl and 4,5,5-Cryptor-4-pentenyl.

Examples of C2-C5 quinil, optionally substituted by one or more Halogens include ethinyl, 1-PROPYNYL, 2-PROPYNYL, 1-butynyl, 3-methyl-1-butenyl, 3-chloro-2-PROPYNYL, 3,3,3-Cryptor-1-PROPYNYL and 4,4,4-Cryptor-2-butenyl.

Examples of C3-C5 cycloalkyl, optionally substituted by one or more Halogens include cyclopropyl, 2,2-dichlorocyclohexyl, 2,2-divorcecare, 2,2,3,3-tetraferriphlogopite, 2,-dichlorocyclohexyl, 2.2-diversilobum, 2,2,3,3-tetrafluorocyclobutanol, cyclobutyl, cyclopentyl and cyclohexyl.

Examples of C4-C5 cycloalkenyl, optionally substituted by one or more halogen, include 2-fluoro-2-cyclopentenyl.

Examples of C2-C6 Alcantara, optionally substituted by one or more halogen, jointly presented R3and R4include ethylene, propylene, trimethylene and tetramethylene.

Examples of C4-C6 Alcantara, optionally substituted by one or more halogen, include 2-Butyrin and 2-penttinen.

Examples of the halogen represented by R5or R14include fluorine, chlorine, bromine and iodine.

Examples of C1-C5 alkyl, optionally substituted by one or more halogen represented by R5, R6, R7, R10, R11, R12, R13, R14, R17, R18, R19, R20or R21include methyl, ethyl, 1-methylethyl, 1-atility, 1,1-dimethylethyl, propyl, 1-methylpropyl, 1-ethylpropyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1,2-dimethylpropyl, 1,1,2-trimethylpropyl, butyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, pentyl, vermeil, chloromethyl, methyl bromide, iodomethyl, deformity, CHLOROFORMATES, bromodifluoromethyl, trifluoromethyl, dichloromethyl, trichloromethyl, 1-chloroethyl, 1-bromacil, 1-Iodate, 1-foretel, 2-chloroethyl, 2-bromacil, 2-Iodate, 2-foretel, 2,2-dottorati, 2,2,2-trif oratel, 2,2,2-trichlorethyl, pentafluoroethyl, 2,2,2-Cryptor-1-chloroethyl, 3-forproper, 3-chloropropyl, 1-fluoro-1-methylethyl, 1-chloro-1-methylethyl, 1-bromo-1-methylethyl, 2-chloro-1,1-dimethylethyl, 1,1-dottorati, 2-fluoro-1,1-dimethylethyl, heptafluoropropyl, 1,1,2,2,3,3-hexaferrites, 4-chlorobutyl, 4-terbutyl, 5-chloropentyl and 5-terpencil.

Examples of C2-C5 alkenyl, optionally substituted by one or more halogen represented by R5, R20or R21include vinyl, 1-methylvinyl, 1-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1,2-dimethyl-1-propenyl, 2-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-2-propenyl, 2,2-defermined, 2-chloro-2-propenyl, 2,2-dichloro-2-propenyl, 2-bromo-2-propenyl, 2,2-dibromo-2-propenyl and 2-fluoro-2-propenyl.

Examples of C3-C5 alkenyl, optionally substituted by one or more halogen represented by R6, R7, R10, R11, R12, R13, R17, R18or R19include 2-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-2-propenyl, 2-chloro-2-propenyl, 2,2-dichloro-2-propenyl, 2-bromo-2-propenyl, 2,2-dibromo-2-propenyl, 2-fluoro-2-propanol and 2,2-debtor-2-propenyl.

Examples of C2-C5 quinil, optionally substituted by one or more halogen represented by R5, R20or R21include ethinyl, 1-PROPYNYL, 2-PROPYNYL and 3,3,3-Cryptor-1-rapinyl.

Examples of C3-C5 quinil, optionally substituted by one or more halogen represented by R6, R7, R10, R11, R12, R13, R17, R18or R19include 1-PROPYNYL, 2-PROPYNYL and 3,3,3-Cryptor-1-PROPYNYL.

Examples of C3-C6 cycloalkyl, optionally substituted with halogen or C1-C3-alkyl represented by R5include cyclopropyl, 1-methylcyclopropyl, 2,2-dichlorocyclohexyl, 2,2-dichloro-1-methylcyclopropyl, 2,2-divorcecare, 2,2-debtor-1-methylcyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

Examples of C3-C6 cycloalkyl, optionally substituted by one or more halogen represented by R6, R7, R10, R11, R12, R13, R14, R17, R18, R19, R20or R21include cyclopropyl, 2,2-dichlorocyclohexyl, 2,2-divorcecare, cyclobutyl, cyclopentyl and cyclohexyl.

Examples of C1-C5 alkoxy, optionally substituted by one or more halogen represented by R5or R14include methoxy, ethoxy, propoxy, triptoreline, bromodifluoromethane, deformedarse, formatosi, CHLOROFORMATES, pentaborate, 2,2,2-triptoreline and 1,1,2,2-tetrafluoroethoxy.

Examples of C3-C6, alkenylacyl, optionally substituted by one or more halogen represented by R5include 1-propene is lexi, 2 propenyloxy and 2,2-debtor-2-propenyloxy.

Examples of C3-C6, alkyloxy, optionally substituted by one or more halogen represented by R5include 2-propenyloxy and 2 butenyloxy.

Examples of (C1-C5 alkoxy, optionally substituted by one or more halogen)C1-C3 alkyl represented by R6, R10, R11or R19include methoxymethyl, ethoxymethyl, 1-methoxyethyl, 1-ethoxyethyl and trifloromethyl.

Examples C1-C5, alkylthio, optionally substituted by one or more halogen represented by R5or R14include methylthio, ethylthio, triptoreline, chlordiftormethane, bromodifluoromethyl, dibrompropamidine, 2,2,2-triptoreline, 1,1,2,2-tetrafluorethylene, pentaverate.

Examples of C3-C5, alkanity, optionally substituted by one or more halogen represented by R5or R14include 2-property and 2,2-debtor-2-propylthio.

Examples of C3-C5, alkylthio, optionally substituted by one or more halogen represented by R5or R14include 2-propylthio, 2-butylthio and 3,3,3-Cryptor-1-PROPYNYL.

Examples of C1-C5 alkylsulfonyl, optionally substituted by one or more halogen represented by R5, R6, R10, R11or R14include methylsulfinyl, ethylsulfinyl and three is cosmeticsurgery.

Examples of C1-C5 alkylsulfonyl, optionally substituted by one or more halogen represented by R5, R6, R10, R11, R14or R19include methylsulphonyl and trifloromethyl.

Examples of C2-C6 alkylsulphonyl, optionally substituted by one or more halogen represented by R5, R6, R7, R10, R11, R14or R19include acetyl, propionyl, 2,2-dimethylpropionic and TRIFLUOROACETYL.

Examples of C2-C5 alkoxycarbonyl represented by R5, R6, R7, R10, R11, R14or R19include methoxycarbonyl, etoxycarbonyl, 1-methylethanolamine and tert-butoxycarbonyl.

Examples trialkylsilyl represented by R19include trimethylsilyl, triisopropylsilyl and tert-butyldimethylsilyl.

Examples of C2-C6 Alcantara, optionally substituted by one or more halogen represented by two groups of CR5or CR5and NR6together include propylene, trimethylene, tetramethylene, ethylenoxy, dimethylene, atalantia, dimethylation.

Examples of C4-C6 Alcantara, optionally substituted by one or more halogen, include 2-butylen and 2-penttinen.

Examples of C2-C6 Alcantara, optionally substituted by one or more halogen, presents joint is R 12and R13include ethylene, propylene, trimethylene and tetramethylene.

Examples of C4-C6 Alcantara, optionally substituted by one or more halogen, include 2-butylen and 2-penttinen.

Examples of the group represented by C(OR19R20R21include 1-hydroxy-1-methylethyl, 1-methyl-1-methoxyethyl and 1-methyl-1-propargyloxy.

Aspects of the present compounds include the following compounds:

connection malononitrile formula (I)in which R1represents hydrogen;

connection malononitrile formula (I)in which R2represents methyl;

connection malononitrile formula (I)in which R1and R2represent hydrogen;

connection malononitrile formula (I)in which R1represents hydrogen, and R2represents methyl;

connection malononitrile formula (I)in which R1represents a C1-C3 alkyl, optionally substituted by one or more halogen, or hydrogen, and R2represents a C1-C3 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, hydrogen or cyano;

connection malononitrile formula (I)in which R1is the Wallpaper hydrogen, and R2represents a C1-C3 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (I)in which R3represents hydrogen;

connection malononitrile formula (I)in which R4represents a C2-C5 of alkenyl, optionally substituted by one or more Halogens;

connection malononitrile formula (I)in which R4represents vinyl;

connection malononitrile formula (I)in which R4is a 2-propenyl;

connection malononitrile formula (I)in which R4represents 2,2-defermined;

connection malononitrile formula (I)in which R4represents a 1-(trifluoromethyl)vinyl;

connection malononitrile formula (I)in which R4represents 3,3-debtor-2-propenyl;

connection malononitrile formula (I)in which R4is a 2,3,3-Cryptor-2-propenyl;

connection malononitrile formula (I)in which R4is a 3,3,3-Cryptor-1-propenyl;

connection malononitrile formula (I)in which R4represents a C2-C5 quinil, optionally substituted by one or more Halogens;

connection malononitrile formula (I)in which R4represents a C1-C5 foralkyl;

connection malononitrile fo the formula (I), in which R4is vermeil;

connection malononitrile formula (I)in which R4represents 2,2-dottorati;

connection malononitrile formula (I)in which R4represents a 2,2,2-triptorelin;

connection malononitrile formula (I)in which R4is pentafluoroethyl;

connection malononitrile formula (I)in which R4is a 3,3,3-cryptochromes;

connection malononitrile formula (I)in which R4is a 2,2,3,3,3-pentafluoropropyl;

connection malononitrile formula (I)in which R4represents C3-C6 cycloalkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (I)in which R4represents 2,2-dichlorocyclohexyl;

connection malononitrile formula (I)in which R4is cyclopropyl;

connection malononitrile formula (I)in which R4is cyclobutyl;

connection malononitrile formula (I), in which each of R3and R4represents a C1-C3 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C3 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, not battelino substituted by one or more halogen, or hydrogen, or R3and R4together represent C2-C6 alcander, optionally substituted by one or more Halogens;

connection malononitrile formula (I)in which R3represents hydrogen and R4represents a C1-C3 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted with halogen, or C2-C5 quinil, optionally substituted by one or more halogen, or R3and R4together form a C2-C6 alcander, optionally substituted by halogen;

connection malononitrile formula (I)in which R3represents hydrogen and R4represents a vinyl or 2-propenyl;

connection malononitrile formula (I)in which R3represents hydrogen and R4represents 2,2-defermined, 1-(trifluoromethyl)vinyl, 3,3-debtor-2-propenyl, 2,3,3-Cryptor-2-propenyl or 3,3,3-Cryptor-1-propenyl;

connection malononitrile formula (I)in which R3represents hydrogen and R4is vermeil, 2,2-dottorati, 2,2,2-triptorelin, 1,1,1,2,2,2-pentafluoroethyl, 3,3,3-cryptochromes or 2,2,3,3,3-pentafluoropropyl;

connection malononitrile formula (I)in which R3represents hydrogen and R4is cyclopropyl, cyclobutyl or 2,2-dichlorocyclohexyl;

link is malononitrile formula (I), in which R1, R2and R3represent hydrogen and R4represents a vinyl or 2-propenyl;

connection malononitrile formula (I)in which R1, R2and R3represent hydrogen and R4represents 2,2-defermined, 1-(trifluoromethyl)vinyl, 3,3-debtor-2-propenyl, 2,3,3-Cryptor-2-propenyl or 3,3,3-Cryptor-1-propenyl;

connection malononitrile formula (I)in which R1and R3represent hydrogen, R2represents methyl and R4represents 2,2-defermined, 1-(trifluoromethyl)vinyl, 3,3-debtor-2-propenyl, 2,3,3-Cryptor-2-propenyl or 3,3,3-Cryptor-1-propenyl;

connection malononitrile formula (I)in which R1, R2and R3represent hydrogen and R4is vermeil, 2,2-dottorati, 2,2,2-triptorelin, pentafluoroethyl, 3,3,3-cryptochromes or 2,2,3,3,3-pentafluoropropyl;

connection malononitrile formula (I)in which R1and R3represent hydrogen, R2represents methyl and R4is vermeil, 2,2-dottorati, 2,2,2-triptorelin, pentafluoroethyl, 3,3,3-cryptochromes or 2,2,3,3,3-pentafluoropropyl;

connection malononitrile formula (I)in which R1, R2and R3represent hydrogen and R4is cyclopropyl, cyclobutyl or 2,2-dichloric propyl;

connection malononitrile formula (I)in which R1represents hydrogen and R2represents a C1-C3 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (I)in which R1represents a C1-C3 alkyl, optionally substituted by one or more halogen, or hydrogen, and R2represents a C1-C3 alkyl, optionally substituted by one or more halogen, C1-C3 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, hydrogen or cyano;

connection malononitrile formula (I), in which each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, or hydrogen, or R3and R4together form a C2-C6 alcander, optionally substituted by one or more Halogens;

connection malononitrile formula (I)in which R3represents hydrogen and R 4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or R3and R4together form a C2-C6 alcander, optionally substituted by one or more Halogens;

connection malononitrile formula (I)in which R1represents hydrogen, R2represents a C1-C3 alkyl, optionally substituted by one or more halogen, or hydrogen, and each of R3 and R4represents a C1-C3 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, or hydrogen, or R3and R4together form a C2-C6 alcander, optionally substituted by one or more Halogens;

connection malononitrile formula (I)in which R1represents a C1-C3 alkyl, optionally substituted by one or more halogen, or hydrogen, R2represents a C1-C3 alkyl, optionally substituted by one or more halogen, C1-C3 alkoxy, not necessarily samewe is hydrated by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, hydrogen or cyano, and each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, or hydrogen, or R3and R4together form a C2-C6 alcander, optionally substituted by one or more Halogens;

connection malononitrile formula (I)in which R1represents hydrogen, R2represents a C1-C3 alkyl, optionally substituted by one or more halogen, or hydrogen, and each of R3and R4represents a C1-C3 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, or hydrogen, or R3and R4together form a C2-C6 alcander, optionally substituted by one or more Halogens;

the connection is giving malononitrile formula (I), in which R1represents a C1-C3 alkyl, optionally substituted by one or more halogen, or hydrogen, R2represents a C1-C3 alkyl, optionally substituted by one or more halogen, C1-C3 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, hydrogen or cyano, R3represents hydrogen and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or C2-C5 alkyl, optionally substituted by one or more halogen, or R3and R4together form a C2-C6 alcander, optionally substituted by one or more Halogens;

connection malononitrile formula (I)in which Z represents NR6X1represents nitrogen, and each of X2X3and X4represents CR5;

connection malononitrile formula (I)in which Z represents oxygen, X1represents nitrogen, and each of X2X3and X4represents CR5;

connection malononitrile formula (I)in which Z represents sulfur, X1represents nitrogen, and each of X2X3and X4represents CR5;

connection malononitrile formula (I)in which Z represents NR6X2represents nitrogen, and each of X1X3and X4represents CR5;

connection malononitrile formula (I)in which Z represents oxygen, X2represents nitrogen, and each of X1X3and X4represents CR5;

connection malononitrile formula (I)in which Z represents sulfur, X2represents nitrogen, and each of X1X3and X4represents CR5;

connection malononitrile formula (I)in which Z represents NR6X1and X2represent nitrogen, and each of X3and X4represents CR5;

connection malononitrile formula (I)in which Z represents NR6X1and X3represent nitrogen, and each of X2and X4represents CR5;

connection malononitrile formula (I)in which Z represents oxygen, X1and X3represent nitrogen, and each of X2and X4represents CR5;

connection malononitrile formula (I)in which Z represents oxygen, X2and X3represent nitrogen, and each is output from the X 1and X4represents CR5;

connection malononitrile formula (I)in which Z represents sulfur, X1and X3represent nitrogen, and each of X2and X4represents CR5;

connection malononitrile formula (I)in which Z represents sulfur, X2and X3represent nitrogen, and each of X1and X4represents CR5;

connection malononitrile formula (I)in which Z represents NR6X1X2and X3represent nitrogen, and X4represents CR5;

connection malononitrile represented by formula (I-i):

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is linked with ethyl;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with a 1-mutilation;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with 1,1-dimethylethyl;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with a 2.2-dimethylpropyl;

connection malononitrile formula (I-i), to the Torah any one of X 3and X4represents a carbon atom that is associated with trifluoromethyl;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with pentatration;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with a 1-methylvinyl;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with atenolol;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with cyclopropyl;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with a 1-methylcyclopropyl;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with propargyloxy;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with a 2-butenyloxy;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with a 3-butenyloxy;

connection malononitrile formula (I-i), where I is th one of X 3and X4represents a carbon atom that is associated with methylthio;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with triptoreline;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with propargite;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with methylsulfinyl;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with triptoreline;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with methylsulfonium;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with triftormetilfullerenov;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with cyano;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with a bromine atom;

connection malononitrile formula (I-i), in which toroi any one of X 3and X4represents a carbon atom that is associated with a chlorine atom;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom that is associated with a fluorine atom;

connection malononitrile formula (I-i), in which any one of X3and X4represents a carbon atom is connected with nitrogroup;

connection malononitrile formula (I-i)in which X3represents a carbon atom that is associated with halogen, cyano or nitro-group;

connection malononitrile formula (I-i)in which X3represents a carbon atom that is associated with C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5-alkylsulfonyl, optionally substituted by one or more halogen, or C1-C5-alkylsulfonyl, optionally substituted by one or more Halogens;

connection malononitrile formula (I-i)in which X3represents a carbon atom that is associated with C1-C5-alkyl, optionally substituted by one or more halogen, C2-C5-alkenyl, optionally substituted by one or more halogen, C2-C5-quinil, optionally substituted by one or more halogen, or C3-C6-quinil, optionally substituted by one or more Halogens;

connection malononitrile formula (I-i), the X 3represents a carbon atom that is associated with a C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, or C3-C6-quinil, optionally substituted by one or more Halogens;

connection malononitrile formula (I-i)in which X4represents a carbon atom that is associated with halogen, cyano or nitro;

connection malononitrile formula (I-i)in which X4represents a carbon atom that is associated with C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5-alkylsulfonyl, optionally substituted by one or more Halogens or C1-C5-alkylsulfonyl, optionally substituted by one or more Halogens;

connection malononitrile formula (I-i)in which X4represents a carbon atom that is associated with C1-C5-alkyl, optionally substituted by one or more halogen, C2-C5-alkenyl, optionally substituted by one or more halogen, C2-C5-quinil, optionally substituted by one or more halogen, or C3-C6-quinil, optionally substituted by one or more Halogens;

connection malononitrile formula (I-i)in which X4predstavljaet a carbon atom, associated with C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, or C3-C6-quinil, optionally substituted by one or more Halogens;

connection malononitrile represented by formula (I-ii):

;

connection malononitrile formula (I-ii)in which Z represents NR6and R6represents ethyl;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is linked with ethyl;

connection malononitrile formula (I-ii)in which Z represents NR6and R6is a 1-methylethyl;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with a 1-mutilation;

connection malononitrile formula (I-ii)in which Z represents NR6and R6represents a 1,1-dimethylethyl;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with 1,1-dimethylethyl;

connection malononitrile formula (I-ii)in which Z represents NR6and R6represents 2,2-dimethylpropyl;

connection malonamic the sludge of the formula (I-ii), in which X4represents a carbon atom that is associated with a 2.2-dimethylpropyl;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with trifluoromethyl;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with pentatration;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with a 1-methylvinyl;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with atenolol;

connection malononitrile formula (I-ii)in which Z represents NR6and R6is a 2-propargyl;

connection malononitrile formula (I-ii)in which Z represents NR6and R6is cyclopropyl;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with cyclopropyl;

connection malononitrile formula (I-ii)in which Z represents NR6and R6is a 1-methylcyclopropyl;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with a 1-methylcyclopropyl;

connection malononitrile formula (I-ii)in which X4represents a carbon atom, is provided with propargyloxy;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with a 2-butenyloxy;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with a 3-butenyloxy;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with methylthio;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with triptoreline;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with propargite;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with methylsulfinyl;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with triptoreline;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with methylsulfonium;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with triftormetilfullerenov;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with cyano;

connection malononitrile formula (I-ii)in which X4p is ecstasy a carbon atom, associated with a bromine atom;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with a chlorine atom;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with a fluorine atom;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with nitro;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with halogen, cyano or nitro;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5-alkylsulfonyl, optionally substituted by one or more halogen, or C1-C5-alkylsulfonyl, optionally substituted by one or more Halogens;

connection malononitrile formula (I-ii)in which X4represents a carbon atom that is associated with C1-C5-alkyl, optionally substituted by one or more halogen, C2-C5-alkenyl, optionally substituted by one or more halogen, C2-C5-quinil, optionally substituted by one or more halogen, or C3-C6-quinil, optionally substituted by one or more Halogens;

connection malononitrile Faure the uly (I-ii), in which X4represents a carbon atom that is associated with a C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, or C3-C6-quinil, optionally substituted by one or more Halogens;

connection malononitrile formula (I-ii)in which Z represents NR6and R6represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 of alkenyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or C3-C6 cycloalkyl, optionally substituted by one or more Halogens;

connection malononitrile represented by formula (II-i):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more of Galaga the AMI, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen;

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4together represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens;

R5represents halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, neobyazatel is substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen, R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-i)in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4C1-C5 alkyl, optionally substituted on the him or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, the group represented by C(OR19R20R21or hydrogen, and

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-i)in which R1and R2provide the amount of hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens,

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens, and

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (II-i)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin,

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens, and

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile represented by formula (II-ii):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optional the part substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

R5represents halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, it is certainly substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-ii)in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted one and the multiple halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more Halogens, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-ii)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 ALK the Nile, optionally substituted by one or more Halogens, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (II-ii)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

The compound represented by formula (II-iii):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl not necessarily replaced by the ne or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

R5represents halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen, and

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen,or hydrogen;

connection malononitrile formula (II-iii)in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more g is loginame, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-iii)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens,

R5is own the th C1-C5 alkyl, optionally substituted by one or more Halogens, and

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (II-iii)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin,

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens, and

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile represented by formula (II-iv):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each of R3and R4not only is em a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

R5represents halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted one or more halogen, C3-C5, alkanity, it is certainly substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-iv)in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen,C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-iv)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (II-i), in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile represented by formula (II-v):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 recloak the Nile, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

R5represents halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 ALK is carbonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-v)in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, not necessarily alseny one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-v)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (II-v)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile, pre is raised by the formula (II-vi):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

R5represents the t of a halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-vi)in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, the group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, it is certainly substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-vi)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (II-vi)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile represented by formula (II-vii):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

R5represents halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, not necessarily Sames the config one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylsulphonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-vii)in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3/sup> and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, the group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-vii)in which R1and R2presented Aut a hydrogen

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (II-vii)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile represented by formula (II-viii):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, zanoli hydrogen

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

R5represents halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optional replacement the military one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-viii)in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more Halogens is, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-viii)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens, and

R5represents a C1-C5 alkyl, neobyazatel is substituted by one or more Halogens;

connection malononitrile formula (II-viii)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile represented by formula (II-ix):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted on the him or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

R5represents halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3 alkyl, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halo is s, C2-C6 alkylaryl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-ix)in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or a few is Kimi halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-ix)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens,

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens, and

R6represents a C1-C5 alkyl, optionally substituted one and the and more Halogens;

connection malononitrile formula (II-ix)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin,

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens, and

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile represented by formula (II-x):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen;

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, n is necessarily substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4,taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens;

R5represents halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more of the Halogens, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-x), in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted one or several is likemy halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen, and

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-x), in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens,

R5represents a C1-C5 alkyl, optionally substituted by one or more halogen, which

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (II-x), in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin,

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens, and

R6represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile represented by formula (II-xi):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or several and halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

R5represents halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5 and is quinitio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-xi)in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, not battelino substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more Halogens, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-xi)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (II-xi)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile represented by formula(II-xii):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more of Galaga the AMI, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

R5represents halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more the Halogens, do the group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-xii)in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alcalali inil, optionally substituted by one or more Halogens, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-xii)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (II-xii)in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile, presents the form of the Oh (II-xiii):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, optionally substituted by one or more Halogens,

R5the present is the focus of a halogen, cyano, nitro, formyl, SF5, C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more Halogens or one or more C1-C3-alkilani, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted one or more halogen, C3-C5, alkanity, optionally substituted by one or more halogen, C3-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, C2-C6 alkylaryl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, optionally substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

p> each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-xiii), in which R1represents hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, or hydrogen,

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C3-C6, alkenylacyl, optionally substituted by one or more halogen, C3-C6, alkyloxy, optionally substituted by one or more halogen, C1-C5, alkylthio, optionally substituted by one or more halogen, C1-C5 alkylsulfonyl, optionally substituted by one or more Halogens, C1-C5 alkylsulfonyl, optionally substituted by one or more halogen, a group represented by C(OR19R20R21or hydrogen,

R19represents a C1-C5 alkyl, it is certainly substituted by one or more halogen, C3-C5 quinil, optionally substituted by one or more halogen, or hydrogen, and

each of R20and R21represents a C1-C5 alkyl, optionally substituted by one or more halogen, or hydrogen;

connection malononitrile formula (II-xiii), in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, or C2-C5 of alkenyl, optionally substituted by one or more Halogens, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens;

connection malononitrile formula (II-xiii), in which R1and R2represent hydrogen,

R3represents hydrogen,

R4represents a 2,2,2-triptorelin, and

R5represents a C1-C5 alkyl, optionally substituted by one or more Halogens.

The following shows the method of obtaining this connection.

Below Het represents a fragment that differs from the R100in the formula (I). Thus, for example, the present compound represented by the formula (I), expressed as follows:

This connection can be obtained, for example, in accordance with CL is blowing method 1 and method 2.

(Method 1)

The method includes the interaction of the compounds (a) and compound (b):

where R1represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, or hydrogen,

R2represents a C1-C5 alkyl, optionally substituted by one or more halogen, C1-C5 alkoxy, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, cyano or hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl, optionally substituted by one or more halogen, C2-C5 quinil, optionally substituted by one or more halogen, C3-C5 cycloalkyl, optionally substituted by one or more halogen, C4-C5 cycloalkenyl, optionally substituted by one or more halogen, or hydrogen,

or R3and R4taken together, represent a C2-C6 alcander, optionally substituted by one or more halogen, or C4-C6 alcander, n is necessarily substituted by one or more halogen, and E1represents a leaving group (e.g. chlorine, bromine, iodine, methanesulfonate, tripterocalyx or toluensulfonate).

The reaction is usually conducted in a solvent in the presence of a base.

The solvent used in the reaction include acid amide, such as N,N-dimethylformamide, simple ether, such as diethyl ether or tetrahydrofuran, organic structurae connection, such as dimethylsulfoxide or sulfolane, halogenated hydrocarbons such as 1,2-dichloroethane or chlorobenzene, aromatic hydrocarbons such as toluene or xylene, and mixtures thereof.

The base used in the reaction includes inorganic base such as sodium hydride, sodium carbonate or potassium carbonate, alkali metal alkoxide, such as tert-piperonyl potassium, and organic base such as 4-dimethylaminopyridine, 1,4-diazabicyclo[2,2,2]octane or 1,8-diazabicyclo[5,4,0]-7-undecene.

The amount of base used in the reaction, usually from 1 to 10 moles per 1 mol of compound (a).

The amount of compound (b)used in the reaction, usually from 1 to 10 moles per 1 mol of compound (a).

The reaction temperature is usually in the range from -20 to 100°C. the reaction Time usually ranges from 1 to 24 hours.

After completion of the reaction the present connection, the pre is raised by the formula (I), can be selected by further processing of the reaction mixture, for example, by adding the reaction mixture into water followed by extraction with an organic solvent, and subsequent concentration of the extract. Selected the present compound represented by the formula (I), if necessary, may be purified by chromatography, recrystallization or the like methods.

(Method 2)

The method includes the interaction of the compound (C) and compound (d):

where E1, R1, R2, R3and R4are as defined above.

The reaction is usually conducted in a solvent in the presence of a base.

The solvent used in the reaction include acid amide, such as N,N-dimethylformamide, simple ether, such as diethyl ether or tetrahydrofuran, organic sulfur-containing compound such as dimethyl sulfoxide or sulfolane, halogenated hydrocarbons such as 1,2-dichloroethane or chlorobenzene, aromatic hydrocarbons such as toluene or xylene, and mixtures thereof.

The base used in the reaction includes inorganic base such as sodium hydride, sodium carbonate or potassium carbonate, alkali metal alkoxide, such as tert-piperonyl potassium, and organic base such as 4-dimethylaminopyridine, 1,4-diazabicyclo[2,2,]octane or 1,8-diazabicyclo[5,4,0]-7-undecene.

The amount of base used in the reaction, usually from 1 to 10 moles per 1 mol of compound (C).

The number of compounds (d)used in the reaction, usually from 1 to 10 moles per 1 mol of compound (C).

The reaction temperature is usually in the range from -20 to 100°C. the reaction Time usually ranges from 1 to 24 hours.

After completion of the reaction, the present compound represented by the formula (I)can be isolated by further processing of the reaction mixture, for example, by adding the reaction mixture into water followed by extraction with an organic solvent, and subsequent concentration of the extract. Selected the present compound represented by the formula (I), if necessary, may be purified by chromatography, recrystallization or the like methods.

Next, reference will be shown the way to obtain an intermediate compound for getting this connection.

(Reference method 1)

where R1and R2are as defined above.

(The first stage)

The compound (f) can be obtained by interaction of the compound (e) with malononitrile.

The reaction is usually conducted in a solvent. The solvent used in the reaction include acid amide, such as N,N-dimethylformamide, a simple ester, Taco is as diethyl ether or tetrahydrofuran, halogenated hydrocarbons such as chloroform, 1,2-dichloroethane or chlorobenzene, aromatic hydrocarbons such as toluene or xylene, an alcohol such as methanol, and mixtures thereof.

If necessary, the reaction can be carried out in the presence of a base. The base used in this reaction include tetrabutylammonium hydroxide.

The amount of base used in the reaction is usually from 0.01 to 0.5 moles per mole of the compound (e).

The number of malononitrile used in the reaction, usually from 1 to 10 moles per 1 mol of compound (e).

The reaction temperature is usually in the range from -20 to 100°C. the reaction Time usually ranges from 1 to 24 hours.

If necessary, the reaction can be conducted while removing from the reaction system, the water formed during the reaction.

After completion of the reaction, the compound (f)can be selected by further processing of the reaction mixture, for example, by adding the reaction mixture into water followed by extraction with an organic solvent, and subsequent concentration of the extract. A dedicated connection (f) if necessary, may be purified by chromatography, recrystallization or the like methods.

The second way

(1) if R2represents a C1-C5 alkyl, optionally substituted with halogen, C2-Salkini, optionally substituted with halogen, or alkenyl, optionally substituted with halogen;

The compound (a) can be obtained by interaction of the compound (f) with the ORGANOMETALLIC compound.

The reaction is usually conducted in a solvent.

The solvent used in the reaction includes a simple ether, such as diethyl ether or tetrahydrofuran, an aromatic hydrocarbon such as toluene or xylene, and mixtures thereof.

ORGANOMETALLIC compound used in the reaction includes magyarkanizsa connection, such as Metalmania iodide, etimani bromide, Isopropylamine bromide, vinylmania bromide, etimani bromide or dimethylamine, organic compound of lithium, such as motility, organic compound of zinc, such as diethylzinc, and the organic compound of copper, such as tricornered.

The amount of ORGANOMETALLIC compound used in the reaction, usually from 1 to 10 moles per 1 mol of compound (f).

If necessary, the reaction can be performed in the presence of a salt of copper. The copper salt used in the reaction include copper iodide(I) and copper bromide(I). The amount of copper salt used in the reaction is usually from 0.05 to 1 mol per 1 mol of compound (f).

The reaction temperature is usually in the range from -20 to 100°C. the reaction Time usually ranges from 1 to 24 is aces.

After completion of the reaction, the compound (a)may be selected by further processing of the reaction mixture, for example, by adding the reaction mixture into water followed by extraction with an organic solvent, and subsequent concentration of the extract. Compound (a) may, if desired, be purified by chromatography, recrystallization or the like methods.

(2) In the case when R2represents hydrogen;

The compound (a) can be obtained by recovering the compound (f).

The reduction is usually carried out in a solvent.

The solvent used in the reaction includes a simple ether, such as diethyl ether or tetrahydrofuran, an aromatic hydrocarbon such as toluene or xylene, an alcohol such as methanol, ethanol or propanol, water, and mixtures thereof.

The reducing agent used in the reaction include sodium borohydride.

The amount of reducing agent used in the reaction, usually from 0.25 to 2 moles per 1 mol of compound (f).

The reaction temperature is usually in the range from 0 to 50°C. the reaction Time usually ranges from seconds to 24 hours.

After completion of the reaction, the compound (a)may be selected by further processing of the reaction mixture, for example, by adding the reaction mixture into water followed EXT the action of an organic solvent, and subsequent concentration of the extract. Compound (a) may, if desired, be purified by chromatography, recrystallization or the like methods.

(3) In the case when R2represents cyano;

The compound (a) can be obtained by reacting compound (f) with a cyanide salt.

The reaction is usually conducted in a solvent.

The solvent used in the reaction includes a simple ether, such as diethyl ether or tetrahydrofuran, an aromatic hydrocarbon such as toluene or xylene, and mixtures thereof.

Cyanide salt used in the reaction includes tetrabutylammonium cyanide.

The amount of cyanide used in the reaction, usually from 1 to 10 moles per 1 mol of compound (f).

The reaction temperature is usually in the range from -20 to 100°C. the reaction Time usually ranges from 1 to 24 hours.

After completion of the reaction, the compound (a) can be selected by further processing of the reaction mixture, for example, by adding the reaction mixture into water followed by extraction with an organic solvent, and subsequent concentration of the extract. Compound (a) may, if desired, be purified by chromatography, recrystallization or the like methods.

(Reference method 2)

The compound (d) can be obtained, for example, the interaction of the compound (b) with small what nonfreedom.

The reaction is usually conducted in a solvent in the presence of a base.

The solvent used in the reaction include acid amide, such as N,N-dimethylformamide, simple ether, such as diethyl ether or tetrahydrofuran, organic structurae connection, such as dimethylsulfoxide or sulfolane, halogenated hydrocarbons such as 1,2-dichloroethane or chlorobenzene, aromatic hydrocarbons such as toluene or xylene, and mixtures thereof.

The base used in the reaction includes inorganic base such as sodium hydride, sodium carbonate or potassium carbonate, alkali metal alkoxide, such as tert-piperonyl potassium, and organic base such as 4-dimethylaminopyridine, 1,4-diazabicyclo[2,2,2]octane or 1,8-diazabicyclo[5,4,0]-7-undecene.

The amount of base used in the reaction, usually from 1 to 10 moles per 1 mol of compound (b).

The number of malononitrile used in the reaction, usually from 1 to 10 moles per 1 mol of compound (b).

The reaction temperature is usually in the range from -20 to 100°C. the reaction Time usually ranges from 1 to 24 hours.

After completion of the reaction, the compound (d) can be selected by further processing of the reaction mixture, for example, by adding the reaction mixture into water with the second extraction with an organic solvent, and subsequent concentration of the extract. Compound (d) may optionally be purified by chromatography, recrystallization or the like methods.

(Reference method 3)

The compound (d) can also be obtained in the following way.

where R3and R4are as defined above.

(The first stage)

The compound (h) can be obtained by interaction of the compound (g) with malononitrile.

The reaction is usually conducted in a solvent in the presence of a base. The solvent used in the reaction include acid amide, such as N,N-dimethylformamide, simple ether, such as diethyl ether or tetrahydrofuran, halogenated hydrocarbons such as 1,2-dichloroethane or chlorobenzene, aromatic hydrocarbons such as toluene or xylene, an alcohol such as methanol, ethanol or isopropanol, and mixtures thereof.

If necessary, the reaction can be carried out in the presence of a base. The base used in the reaction includes tetrabutylammonium hydroxide.

The amount of base used in the reaction is usually from 0.01 to 0.5 moles per 1 mol of compound (g).

The number of malononitrile used in the reaction, usually from 1 to 10 moles per 1 mol of compound (g).

The reaction temperature is usually from -20 to 200°C. the reaction Time usually varies in the range of the region from 1 to 24 hours.

If necessary, the reaction can be conducted while removing from the reaction system, the water formed during the reaction.

After completion of the reaction, the compound (h)can be selected by further processing of the reaction mixture, for example, by adding the reaction mixture into water followed by extraction with an organic solvent, and subsequent concentration of the extract. Compound (h) may optionally be purified by chromatography, recrystallization or the like methods.

(Second stage)

The compound (d) can also be obtained by the interaction of the compound (h) with a reducing agent.

The reaction is usually conducted in a solvent.

The solvent used in the reaction includes alcohol, such as methanol, ethanol, isopropyl alcohol or tert-butyl alcohol, simple ester, such as diethyl ether or tetrahydrofuran, halogenated hydrocarbons such as 1,2-dichloroethane or chlorobenzene, aromatic hydrocarbons such as toluene or xylene, and mixtures thereof.

The reducing agent used in the reaction include sodium borohydride, lithium borohydride and diisopropylaminoethyl.

The amount of reducing agent used in the reaction, depending on the type of reducing agent is usually from 0.25 to 5 moles per 1 mol of compound (h).

The reaction temperature is usually located is in the range from -20 to 100° C. the reaction Time usually ranges from 1 to 24 hours.

After completion of the reaction, the compound (d) can be selected by further processing of the reaction mixture, for example, by adding the reaction mixture into water followed by extraction with an organic solvent, and subsequent concentration of the extract. Compound (d) may optionally be purified by chromatography, recrystallization or the like methods.

(Reference 4)

The compound (c) can be obtained from compound (i), for example, in accordance with the following scheme:

where E1, R1and R2are as defined above, and E2represents a leaving group (e.g. chlorine, methoxy, ethoxy, 1-imidazolyl, 1-pyrazolyl, dimethylamino, 1-piperidyl, or N-methyl-N-methoxyamino.

That is, the compound (e) can be obtained by interaction of the compound (i) with an ORGANOMETALLIC compound represented by R1-M (for example, magnetogenesis connection, such as Metalmania iodide, etimani bromide, Isopropylamine bromide, vinylmania bromide, etonline bromide or dimethylamine, organolithium compound, such as motility, tsinkorganicheskih connection, such as diethylzinc, or organic compound of copper, such as trip ormalised), or a reducing agent (for example, sociallyengaged or diisobutylaluminium).

The compound (j) can be obtained by the interaction of the compounds (i ORGANOMETALLIC compound represented by R1-M (for example, magnetogenesis connection, such as Metalmania iodide, etimani bromide, Isopropylamine bromide, vinylmania bromide, etonline bromide or dimethylamine, organolithium compound, such as motility, tsinkorganicheskih connection, such as diethylzinc, or organic compound of copper, such as tricornered), or a reducing agent (for example, sociallyengaged or diisobutylaluminium).

In addition, the compound (c) can be obtained by halogenoalkanes (for example, by interacting with acidic halogenation agent such as chloride thionyl or phosphorus oxychloride) or sulfonation (for example, by reacting with the anhydride triftormetilfullerenov acid, methanesulfonamido or acid chloride toluensulfonate acid in the presence of a base) of the compound (j).

The compound (e) can also be obtained by the interaction of the compounds (j), where R2represents hydrogen, i.e. the compound (j-1), oxidant (e.g., chromate, a mixture of dimethyl sulfoxide/oxalicacid or manganese dioxide).

(Reference method 5)

CPE and compounds (i), the compound (i-1) can be obtained, for example, in accordance with the method described in Journal of Chemical Society, Perkin Trans., 14, 1716, 2001, by the method shown in the following diagram:

where R5-1independently represents a C1-C5 alkyl, optionally substituted with halogen, C3-C6 cycloalkyl, optionally substituted with halogen, C1-C5 alkylsulfonyl, optionally substituted with halogen, C1-C5 alkylsulfonyl, optionally substituted with halogen, C2-C6 alkylaryl, optionally substituted with halogen, C2-C5 alkoxycarbonyl, optionally substituted with halogen, cyano, nitro or hydrogen, and E3represents methoxy or ethoxy.

(Reference method 6)

Among the compounds (j), the compound (j-2) can be obtained, for example, in accordance with the method shown in the following diagram:

[where R1, R2and R5-1are as defined above, and E4represents a protective group (for example, a group tetrahydropyran-2-yl and so on).

(Reference method 7)

Among compounds (i) compound (i-2), (i-3) and (i-4) can be obtained, for example, in accordance with the method shown in the following diagram:

where E1and E3are as defined above, R6-1represents a C1-C5 alkyl, optionally substituted with halogen, C3-C6 al the sludge, optionally substituted with halogen, C2-C5 of alkenyl, optionally substituted with halogen, or quinil, optionally substituted with halogen, R5-2independently represents a C1-C5 alkyl, optionally substituted with halogen, C3-C6 cycloalkyl, optionally substituted with halogen, or hydrogen, and R6-2represents a C1-C5 alkyl, optionally substituted with halogen, C2-C5 of alkenyl, optionally substituted with halogen, C2-C5 quinil, optionally substituted with halogen, C3-C6 cycloalkyl, optionally substituted with halogen, (C1-C5, alkyloxy, optionally substituted with halogen)C1-C3 alkyl, C1-C5 alkylsulfonyl, optionally substituted with halogen, C1-C5 alkylsulfonyl, optionally substituted with halogen, C2-C6 alkylaryl, optionally substituted with halogen, C2-C5 alkoxycarbonyl, optionally substituted with halogen, a group represented by C(=X5)NR12R13(where X5, R12and R13are as defined above)or a group represented by (CH2)mQ (where m and Q are as defined above).

(Reference 8)

Among the compounds (j), the compound (j-3) can be obtained, for example, by the method shown in the following diagram:

where E4and R6-1are as defined above, X2-1represents oxygen, sulfur or NR 6-1, R5-3represents a C1-C5 alkyl optionally substituted with halogen or C3-C6 cycloalkyl, optionally substituted with halogen, and R5-4represents a halogen or hydrogen.

(Reference method 9)

Among the compounds (e), the compound (e-1) can be obtained in accordance with the method, for example, described in Chem.Heterocycl.Compd.(Engl.Transl.), 28, 53, 1992, for example, by the method shown in the following diagram.

where R1is the same as defined above, R5-5represents a C1-C5 alkyl, optionally substituted with halogen, C3-C6 cycloalkyl, optionally substituted with halogen, halogen or hydrogen, and R6-3represents a C1-C5 alkyl, optionally substituted with halogen, C3-C6 cycloalkyl, optionally substituted with halogen, C2-C5 of alkenyl optionally substituted with halogen, or C2-C5 quinil, optionally substituted with halogen.

(Reference method 10)

Among the compounds (e), the compound (e-2) can be obtained in accordance with the method described, for example, Heterocycles, 23, 1759, (1985), for example, by the method shown in the following diagram.

where R1, R5-5and R6-1are as defined above.

(Reference method 11)

Among compounds (i), the compound (i-5) can be obtained in accordance with the method described, n is the sample, in JP-A 2001-58979, for example, by the method shown in the following diagram:

where E1is the same as defined above, R5-7represents a C1-C5 alkyl, optionally substituted by halogen, or C3-C6 cycloalkyl, optionally substituted with halogen, X2-2represents oxygen, sulfur or NR6-4, R6-4represents a C1-C5 alkyl, optionally substituted with halogen, C3-C6 cycloalkyl, optionally substituted with halogen, C2-C5 of alkenyl, optionally substituted with halogen, or C2-C5 quinil, optionally substituted with halogen, and E5represents methyl or ethyl.

(Reference method 12)

Among the compounds (c), compounds (c-1) and (c-2) can be obtained, for example, in accordance with the method shown in the following diagram:

where E1E2, R1and R2are as defined above, and R5-8represents a C1-C5 alkyl, optionally substituted with halogen, C3-C6 cycloalkyl, optionally substituted with halogen, C2-C5 of alkenyl, optionally substituted with halogen, or C2-C5 quinil.

(Reference method 13)

Among compounds (i) compound (i-6) and (i-7) can be obtained, for example, in accordance with the method shown in the following diagram:

where E4it is the same as defined above, R5-9represents a C1-C5, alkyloxy, optionally substituted with halogen, C2-C5, alkenylacyl, optionally substituted with halogen, C2-C5, alkyloxy, optionally substituted with halogen, C1-C5, alkylthio, optionally substituted with halogen and Hal independently represents a halogen, such as chlorine or bromine.

(Reference method 14)

Among compounds (i), the compound (i-9) can be obtained, for example, in accordance with the method shown in the following diagram:

where E4and R5-3are as defined above, and X2-3represents oxygen or sulphur.

(Reference method 15)

Among the compounds (C) the compound (C-3) can be obtained in accordance with the method described, for example, in JP-A 55-27042, for example, by the method shown in the following diagram:

where R1, R2E1E2and R5-3are as defined above.

(Reference method 16)

Compounds (c), (e), (i) and (j), in which X1represents nitrogen, each of X2X3and X4represents CR5and Z represents NR6that represent the pyrazole can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Cheie, Hetarene III, Teil.3, p.399-710.

(Reference method 17)

Compounds (c), (e), (i) and (j), in which X1represents a nitrogen atom, each of X2X3and X4represents CR6and Z represents an oxygen atom, which are isoxazol can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.1, p.45-204.

(Reference method 18)

Compounds (c), (e), (i) and (j), in which X1represents nitrogen, each of X2X3and X4represents CR5and Z represents sulfur, which are isothiazol can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.1, p.668-788.

(Reference method 19)

Compounds (c), (e), (i) and (j), in which X2represents nitrogen, each of X1X3and X4represents CR5and Z represents NR6that represent imidazole, can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.3, p.1-192.

(Reference method 20)

Compounds (c), (e), (i) and (j), in which X2represents nitrogen, each of X1X3and X4represents CR5and Z represents oxygen, which are 1,3-oxazol, can be synthesized is in accordance with the method, described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.1, p.891-1012.

(Reference method 21)

Compounds (c), (e), (i) and (j), in which X2represents nitrogen, each of X1X3and X4represents CR5and Z represents sulfur, which are 1,3-thiazole, can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.3, p.1-361.

(Reference method 22)

Compounds (c), (e), (i) and (j), in which X1and X3represent nitrogen, each of X2and X4represents CR5and Z represents oxygen, which are 1,2,4-oxadiazol, can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.3, p.409-518.

(Reference method 23)

Compounds (c), (e), (i) and (j), in which X2and X3represent nitrogen, each of X1and X4represents CR5and Z represents oxygen, which represent 1,3,4-oxadiazol, can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.3, p.526-630.

(Reference method 24)

Compounds (c), (e), (i) and (j), in which X1and X3represent nitrogen, each of X2and X4represents CR5and Z represents sulfur, which are 1,24-thiadiazole, can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.4, p.105-148.

(Reference method 25)

Compounds (c), (e), (i) and (j), in which X1and X4represent nitrogen, each of X2and X3represents CR5and Z represents sulfur, which are 1,2,5-thiadiazole, can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.4, p.152-168.

(Reference method 26)

Compounds (c), (e), (i) and (j), in which X2and X3represent nitrogen, each of X1and X4represents CR5and Z represents sulfur, which represents a 1,3,4-thiadiazole, can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.4, p.189-298.

(Reference method 27)

Compounds (c), (e), (i) and (j), in which X1and X2represent nitrogen, each of X3and X4represents CR5and Z represents NR6who are 1,2,3-triazole, can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.4, p.305-389.

(Reference method 28)

Compounds (c), (e), (i) and (j), in which X1and X3represent nitrogen, each of X2and X4represents CR5and Z pre which represents an NR 6that represents a 1,2,4-triazole, can be synthesized in accordance with the method described in Houben-Weyl, Methods der Organischen Chemie, Hetarene III, Teil.4, p.479-586.

Insects against which the present compounds possess regulatory action include harmful arthropods, such as insects and mites, and harmful nematodes. More specifically, examples are listed below.

Hemiptera (Polacrilin):

Delphacidae, such asLaodelphax striatellus,Nilaparvata lugens,Sogatella furciferaand the like,

Deltocephalidae, such asNephotettix cincticeps,Nephotettix virescensand the like,

Aphididae, such asAphis gossypii,Myzus persicaeand the like,

Pentatomidae and Alydidae, such asNezara antennata,Riptortus clavetus,Plautia stali,Halyomorpha mista,Eysarcoris lewisi,Eysarcoris parvusand so forth,

Aleyrodidae, such asTrialeurodes vaporariorum,Bemisia argentifoliiand the like,

Diaspididae, Coccidae and Margarodidae, such asAonidiella aurantii,Comstockaspis perniciosa,Unaspis citri,Ceroplastes rubens,Icerya purchasiand the like,

Tingidae,

Psyllidae, and the like;

Lepidoptera (Butterflies):

Pyralidae such asChilo suppressalis,Cnaphalocrocis medinalis,Notarcha derogata,Plodia interpunctellaand the like,

Noctuidae, such asSpodoptera litura,Pseudaletia separata, Trichoplusia spp., Heliothis spp., Helicoverpa spp. and the like,

Pieridae such asPieris rapaeand the like,

Tortricidae such as Adoxophyes spp.,Grapholita molesta,Cydia pomonellaand the WMD like that,

Carposinidae such asCarposina niponensisand the like,

Lyonetiidae, such as Lyonetia spp. and the like,

Lymantriidae such as Lymantria spp., Euproctis spp. And the like,

Yponomeutidae such asPlutella xylostellaand the like,

Gelechiidae such asPectinophora gossypiellaand the like,

Arctiidae such asHyphantria cuneaand the like,

Tineidae such asTinea translucens,Tineola bisselliellaand the like;

Diptera (Flies):

Culicidae, such asCulex pipiens pallens,Culex tritaeniorhynchus,Culex quinquefasciatusand the like,

Aedes spp., such asAedes aegypti,Aedes albopictusand the like,

Anopheles spp., such asAnopheles sinensisand the like,

Chironomidae,

Muscidae such asMusca domestica,Muscina stabulansand the like,

Calliphoridae,

Sarcophagidae,

Fanniidae,

Anthomyiidae such asDelia platura,Delia antiquaand the like,

Tephritidae,

Drosophilidae,

Psychodidae,

Simuliidae,

Tabanidae,

Stomoxys spp.,

Agromyzidae, and the like;

Coleoptera:

Flea dlinnoyu, such asDiabrotica virgifera virgifera,Diabrotica undecimpunctata howardiand the like,

Scarabaeidae, such asAnomala cuprea,Anomala rufocupreaand the like,

Rhynchophoridae, Curculionidae and Bruchidae, such asSitophilus zeamais,Lissorhoptrus oryzophilus,Callosobruchus chienensisand the like,

Tenebrionidae, such asTenebrio molitor,Tribolium castaneumand the like,

Chrysomelidae, such asOulema oryzae,Aulacophora femoralis,Phyllotreta striolata,Leptinotarsa decemlineat

Anobiidae,

Epilachna spp., such asEpilachna vigintioctopunctataand like Lyctidae,

Bostrychidae,

Cerambycidae,

Paederus fuscipesand the like;

Blattaria:Blattella germanica,Periplaneta fuliginosa,Periplanetaamericana,Periplaneta brunnea,Blatta orientalisand the like;

Thysanoptera:Thrips palmi,Thrips tabaci,Frankliniella occidentalis,Frankliniella intonsaand the like;

Hymenoptera (Hymenoptera):

Formicidae, Vespidae, Betilidae,

Tenthredinidae, such asAthalia japonicaand the like;

Orthoptera):

Gryllotalpidae, Acrididae, and the like;

Aphaniptera:Ctenocephalides felis,Ctenocephalides canis,Pulex irritans,Xenopsylla cheopisand the like;

Anoplura:Pediculus humanus corporis,Phthirus pubis,Haematopinus eurysternus,Dalmalinia ovisand the like;

Isoptera:Reticulitermes speratus,Coptotermes formosanusand the like;

Acarina:

Tetranychidae such asTetranychus urticae,Tetranychus kanzawai,Panonychus citri,Panonychus ulmi, Oligonychus spp. and the like,

Eriophyidae such asAculops pelekassi,Aculus schlechtendaliand the like,

Tarsonemidae such asPolyphagotarsonemus latusand so forth,

Tenuipalpidae,

Tuckerellidae,

Ixodidae such asHaemaphysalis longicornis,Haemaphysalis flava,Dermacentor variabilis,Ixodes ovatus,Ixodes persulcatus,Boophilus microplusand the like,

Acaridae such asTyrophagus putrescentiaeand the like,

Epidermoptidae, such asDermatophagoides farinae,Dermatophagoides ptrenyssnusand the like,

Cheyletidae such asCheyletus eruditus,Cheyetus malaccensis ,Cheyletus mooreiand the like,

Dermanyssidae and the like;

Araneae:Chiracanthium japonicum,Latrodectus hasseltiiand the like;

Chilopoda:Thereuonema hilgendorfi,Scolopendra subspinipesand the like;

Diplopoda:Oxidus gracilis,Nedyopus tambanusand the like;

Isopoda:Armadillidium vulgareand the like;

Gastropoda:C limax vaginal marginatus,C limax vaginal flavusand the like;

Nematoda (Nematodes):Pratylenchus coffeae,Pratylenchus fallax,Heterodera glycines,Globodera rostochiensis,Meloidogyne hapla,Meloidogyne incognitaand the like.

Although the pesticide composition of the present invention may constitute in itself this connection, it is usually introduced into the formulation by mixing with a solid carrier, liquid carrier and/or liquid carrier and, optionally, if necessary, adding a surfactant and other adjuvants for formulation. That is, the pesticide composition of the present invention typically contains the present compound and further comprises an inert carrier. Such a composition includes an emulsion, oil, shampoo, liquid preparation, a powder, a wetting agent, a granule, a paste, a microcapsule, a foam, an aerosol, a drug on the basis of carbon dioxide, the tablet and the drug-based resin. These drugs can be used in the form of toxic baits, pesticides spiral, electric PE Tiziano plate, Smoking drug, fumigant and preparation in the form of a sheet.

The drug pesticide composition of the present invention usually contains from 0.1 to 95% by weight of this connection.

The solid carrier used for formulation, includes fine powder or granules of clays (e.g. kaolin clay, diatomaceous earth, bentonite, clay fubasami, acid clay, etc), synthetic hydrated silicon oxide, talc, ceramics, other inorganic minerals (e.g. sericite, quartz, sulfur, activated carbon, calcium carbonate, hydrated silicon dioxide and so on) and chemical fertilizers (e.g. ammonium sulfate, ammonium phosphate, ammonium nitrate, ammonium chloride, urea and so on).

The liquid carrier include aromatic and aliphatic hydrocarbons (e.g. xylene, toluene, alkylnaphthalene, phenylxylylethane, kerosene, gasoil, hexane, cyclohexane, etc.), halogenated hydrocarbons (e.g. chlorobenzene, dichloromethane, dichloroethane, trichloroethane, etc.), alcohols (e.g. methanol, ethanol, isopropyl alcohol, butanol, hexanol, benzyl alcohol, ethylene glycol, etc.), ethers (e.g. diethyl simple ether, dimethyl simple ether of ethylene glycol, onomatology simple ether of diethylene glycol, monotropy simple ether of diethylene glycol, onomatology simple ether profiling ikola, tetrahydrofuran, dioxane, etc.), esters (e.g. ethyl acetate, butyl acetate, etc.), ketones (e.g. acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, etc.), NITRILES (e.g. acetonitrile, isobutyronitrile etc), sulfoxidov (for example, dimethyl sulfoxide and so on), acid amides (e.g. N,N-dimethylformamide, N,N-dimethylacetamide, etc), vegetable oil (e.g. soybean oil, cotton oil, etc.), plant oils (for example, orange oil, oil isopole, lemon oil etc) and water.

The gaseous medium includes gaseous butane, gaseous chlorofluorocarbon, liquefied petroleum gas (LPG), dimethyl simple ether and gaseous carbonic acid.

Surfactant include salts alkylsulfate ethers, alkyl sulphonates, alkylarylsulphonates, alkilammonia ethers and their polyoxyethylenated products, ethers of polyethylene glycol, esters of polyhydric alcohols and derivatives, sugar alcohols.

Other auxiliary additives for preparations include binders, dispersing agents and stabilizers, for example, specifically, casein, gelatin, polysaccharides (e.g. starch, Arabic gum, cellulose derivatives, alginine acid etc), lignin derivatives, bentonite, sugars, synthetic moderator the appropriate polymers (for example, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, etc.), PAP (acidic isopropylacetate), BHT (2,6-di-tert-butyl-4-METHYLPHENOL), BHA (mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oils, mineral oils, fatty acids and esters of fatty acids.

The material basis for drug-based resin includes polyvinyl chloride and polyurethane. These core materials can be added, if necessary, a plasticizer such as an ester of phthalic acid (e.g., dimethylphthalate, dioctylphthalate etc), an ester of adipic acid and stearic acid.

Drug-based resin can be obtained by mixing until a homogeneous mass of this compound with the resin using conventional mixing device followed by molding, such as injection molding, extrusion or pressing. The resulting drug-based resin may be molded, if necessary, in the form of a plate, foil, strip, grid, threads and the like through an additional stage of forming, cutting and the like. Such preparations based resin can be produced in the form of a collar for an animal, clips inserted into the ear of the animal drug in the form of a sheet, a pencil or props for gardening.

The base material for poison prima the CI includes the powder grain, vegetable oil, sugar and crystalline cellulose. If necessary, the base material may be added an antioxidant, such as dibutylaminoethanol or nordihydroguaiaretic acid, preservatives such as dehydroacetic acid, an agent for preventing erroneous eating children and Pets, attracting pests flavor such as cheese flavor, onion flavor or peanut butter.

The pesticide composition of the present invention can be used by direct application to pests and/or habitats of pests (e.g., plants, animals, soil, etc).

When the pesticidal composition of the present invention is used for controlling pests of agriculture and forestry, the applied amount typically ranges from 1 to 100000 g/ha, preferably from 10 to 1000 g/ha of active ingredient. When the pesticidal composition of the present invention is in the form of an emulsion, a wetting agent, a flowing agent, or microcapsules, it is usually used diluted with water, containing from 1 to 10000 ppm of the active ingredient. When the pesticidal composition of the present invention is in the form of powder or granules, it is usually used by itself. These drugs can be sprayed on plants, to the which need to be protected from pests. In addition, these drugs can cultivate the soil to control pests living in the soil. The beds before planting plants or holes for plants or the lower part of the plants at planting can also be treated with these drugs. In addition, leaf preparations pesticide composition of the present invention can be applied by wrapping them around the plants, placing close to the plants, placing them on the soil surface at the lower parts of the plant or the like.

When the pesticidal composition of the present invention is used for pest control during the epidemic, the damage amount is usually from 0.001 to 100 mg/m3active ingredient for application in space and from 0.001 to 100 mg/m2the active ingredient for use on a flat surface. The pesticide composition in the form of emulsions, wetting agent or fluid agent is usually applied in diluted form, containing from 0.01 to 10,000 parts per million of active ingredient. The pesticide composition in the form of oil, aerosol, "Smoking" of a drug or poisonous bait is commonly used as such.

When the pesticidal composition of the present invention is used to control parasites living inside livestock such as cow, horse, pig, sheep, to the for or chicken, or in small domestic animals such as dog, cat, rat or mouse, you can use the usual methods adopted in veterinary medicine. Specifically, when it is assumed systematic regulation, the pesticide composition is administered, for example, in the form of tablets, mix with food, suppository or injection (e.g., intramuscularly, subcutaneously, intravenously, intraperitoneally, etc.). When it is assumed non-system regulation, the method of application of the pesticide composition of the present invention includes spraying, pouring or application in the form of spots pesticide composition in the form of an oil or aqueous liquid, wash the animal with the use of the pesticide composition in the form of the drug shampoo and wearing the animal collar or ear clips made from pesticide composition in the form of drug-based resin. With the introduction of the animal, the amount of this compound usually ranges from 0.01 to 1000 mg per 1 kg body weight of the animal.

The pesticide composition of the present invention can be used in mixture or in combination with other insecticides, nematicides, acaricides, bactericides, herbicides, plant growth regulators, synergists, fertilizers, soil conditioners, animal feed, and the like.

The active ingredient of this insecticide or acaricide includes pyrethroids the e connection such as allethrin, tetramethrin, prallethrin, phenothrin, resmethrin, cyphenothrin, permethrin, cypermethrin, alpha-cypermethrin, Zeta-cypermethrin, deltamethrin, tralomethrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda cyhalothrin, flumethrin, imiprothrin, etofenprox, fenvalerate, esfenvalerate, fenpropathrin, selflove, bifenthrin, transfluthrin, flucythrinate, teaflavin, acrinathrin and tefluthrin; organic phosphorus compounds such as dichlorvos, fenitrothion, vianovo, profenofos, sulprofos, pentat, isoxathion, tetrachlorvinphos, fenthion, chlorpyrifos, diazinon, Arafat, terbufos, Fort, chlorethoxyfos, fosthiazate, ethoprophos, cadusafos, mitigation; urethane compounds such as propoxur, carbaryl, methoxamine, fenobucarb, methomyl, thiodicarb, alankar, benfuracarb, oxamyl, aldicarb and Medicare; connection benzoylferrocene, such as lufenuron, chlorfluazuron, hexaflumuron, diflubenzuron, triflumuron, teflubenzuron, flufenoxuron, fluazuron, novaluron and treasure; substances such juvenile hormone, such as pyriproxyfen, methoprene, hydroprene and fenoxycarb; neonicotinoid compounds such as acetamiprid, nitenpyram, thiacloprid, thiamethoxam and dinotefuran, the compounds N-phenylpyrazole, such as acetool and ethiprole; connection benzoylhydrazone, such as tebufenozide, chromafenozide is, methoxyfenozide and halogenated; diafenthiuron; pymetrozine; flonicamid; triazamate; buprofezin; spinosad; emamectin benzoate; chlorfenapyr; indoxacarb Mr; pyridalyl; cyromazine; fenpyroximate; tebufenpyrad; elfenberg; pyridaben; pyrimidifen; fluoroperm; etoxazole; fenazaquin; acequinocyl; hexythiazox; clofentezine; fenbutatin oxide; dicofol; propargyl; abamectin; milbemectin; amitraz; cartap; bensultap; thiocyclam; endosulfan; spirodiclofen; spiromesifen and azadirachtin.

The active ingredient of such a bactericide includes compounds of strobilurin, such as Apoksiomen; organic phosphorus compounds such as tolclofos-methyl; compound of asola, such as triflumizole, peyratout and difenoconazole; phtalic; flutolanil; validamycin; provenzal; declomycin; pencycuron; dazomet; kagamitan; IBP; pyroquilon; oxolinic acid; tricresol; parison; mepronil; EDDP; isoprothiolane; cropropamide; declocked; parameter; fludyoksonil; procymidon and diatopical.

Examples

The present invention will be explained in more detail using the following examples of the preparation, examples preparative forms and experimental examples, but the invention is not restricted by them.

First will be described the examples of the preparation of these compounds.

Example obtain 1

of 1.32 g of the hydrochloride of 3-tert-butyl-5-(chloro who yl)-1H-pyrazole and 1.13 g of (3,3,3-cryptochromes)malononitrile was dissolved in 21 ml of N,N-dimethylformamide and then added with ice cooling of 1.93 g of potassium carbonate. The mixture was stirred at room temperature for 3 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was recrystallized from a mixture of hexane-ethyl acetate, receiving 1.35 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (1)).

1H-NMR (CDCl3, TMS, δ (ppm)): 1,32 (9H, c), 2,18-of 2.27 (2H, m), 2,44 at 2.59 (2H, m)to 3.34 (2H, c), 6,16 (1H, c), 10,19 (1H, users)

Example of getting 2

2,52 g of the hydrochloride of 5-(chloromethyl)-3-tert-butyl-1-methyl-1H-pyrazole and 1.83 g of (3,3,3-cryptochromes)malononitrile was dissolved in 25 ml of N,N-dimethylformamide and then added with ice cooling 3.12 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was recrystallized from a mixture of hexane-ethyl acetate, receiving of 0.44 g of compound represented by the following formula:

(hereinafter referred to as the present compounds is s (2)).

1H-NMR (CDCl3, TMS, δ (ppm)):of 1.30 (9H, c), 2,25-to 2.29 (2H, m), 2,49-2,61 (2H, m)to 3.34 (2H, c), 3,85 (3H, c), 6,23 (1H, c)

Example for the preparation of 3

2,13 g of the hydrochloride of 3-tert-butyl-5-(chloromethyl)-1-(2,2,2-triptorelin)-1H-pyrazole and 1.18 g of (3,3,3-cryptochromes)malononitrile was dissolved in 21 ml of N,N-dimethylformamide and then added with ice cooling 2,02 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 1,49 g of compound represented by the following formula:

(hereinafter referred to as the present compound (3)).

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.39 (9H, c), and 2.26-to 2.29 (2H, m), 2,45-of 2.56 (2H, m), 3,29 (2H, c), of 4.77 (2H, HF), 6,17(1H, c)

Example 4

1.12 g of 3-tert-butyl-5-(chloromethyl)isoxazol and of 1.30 g of (3,3,3-cryptochromes)malononitrile was dissolved in 24 ml of N,N-dimethylformamide and then added with ice cooling of 2.21 g of potassium carbonate. The mixture was stirred at room temperature for 3 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, su is or over anhydrous magnesium sulfate, was filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel and then recrystallized from a mixture of hexane-ethyl acetate, getting 0.55 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (4)).

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.35 (9H, c), and 2.26-to 2.29 (2H, m), 2,48-2,60 (2H, m), of 3.48 (2H, c), 6.35mm (1H, c)

Example of getting 5

of 1.36 g of 3-tert-butyl-5-(chloromethyl)isothiazole and of 1.37 g of (3,3,3-cryptochromes)malononitrile was dissolved in 27 ml of N,N-dimethylformamide and then added with ice cooling to 2.35 g of potassium carbonate. The mixture was stirred at room temperature for 5 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel and then recrystallized from a mixture of hexane-ethyl acetate, getting 0,89 g of compound represented by the following formula:

(hereinafter referred to as the present compound (5)).

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.34 (9H, c), and 2.26-of 2.30 (2H, m), 2,49-2,61 (2H, m)to 3.38 (2H, c), 6,11 (1H, c)

An example of obtaining 6

0,69 g 5-tert-butyl-3-(chloromethyl)and is oxazole and 0.65 g of (3,3,3-cryptochromes)malononitrile was dissolved in 12 ml of N,N-dimethylformamide and then added with ice cooling to 1.11 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel and then recrystallized from a mixture of hexane-ethyl acetate, getting 0.36 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (6)).

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.37 (9H, c), 2,25-to 2.29 (2H, m), 2,49-2,60 (2H, m)to 3.38 (2H, c), 6,10 (1H, c)

Example of getting 7

of 0.91 g of the hydrochloride of 1-tert-butyl-4-(chloromethyl)-1H-pyrazole and 0.81 g of (3,3,3-cryptochromes)malononitrile was dissolved in 10 ml of N,N-dimethylformamide and then added with ice cooling to 1.38 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel and then recrystallized from a mixture of hexane-ethyl acetate, getting 0.34 g of the compound represented by the following formula

(hereinafter referred to as the present compound (7)).

1H-NMR (CDCl3, TMS, δ(ppm)): 1,60 (9H, c), 2,17-of 2.21 (2H, m), 2,48-to 2.57 (2H, m), 3,20 (2H, c), 7,55 (1H, c), to 7.61 (1H, c)

Example obtain 8

2,39 g of the hydrochloride of 1-benzyl-4-(chloromethyl)-1H-pyrazole and 1.59 g of (3,3,3-cryptochromes)malononitrile was dissolved in 30 ml of N,N-dimethylformamide and then added with ice cooling 2.76 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel and then recrystallized from a mixture of hexane-ethyl acetate, receiving of 1.94 g of compound represented by the following formula:

(hereinafter referred to as the present compound (8)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,15-only 2.91 (2H, m), 2,44-of 2.56 (2H, m), 3,18 (2H, c), 5,32 (2H, c), 7,21-of 7.23 (2H, m), 7,30-7,38 (3H, m), of 7.48 (1H, c), EUR 7.57 (1H, c)

Example of getting 9

1.04 g of 2-tert-butyl-4-(chloromethyl)-1,3-oxazole and 0.97 g of (3,3,3-cryptochromes)malononitrile was dissolved in 24 ml of N,N-dimethylformamide and then added with ice cooling 1.66 g of potassium carbonate. The mixture was stirred at room temperature is within 3 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.64 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (9)).

1H-NMR (CDCl3, TMS, δ (ppm)): 1,32 (9H, c), 2,31 to 2.35 (2H, m), of 2.51-2,60 (2H, m)of 3.25 (2H, c), to 7.64 (1H, c)

Example 10

of 1.02 g of the hydrochloride of 4-(chloromethyl)-1,3-thiazole and 0.97 g of (3,3,3-cryptochromes)malononitrile was dissolved in 18 ml of N,N-dimethylformamide and then added with ice cooling 1.66 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0,93 g of compound represented by the following formula:

(hereinafter referred to as the present compound (10)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,29-of 2.34 (2H, m), 2,52-2,63 (2H, m), of 3.56 (2H, c), was 7.45 (1H, c), 8,86 (1H, c)

Example n the receipt of 11

of 0.48 g of 4-(chloromethyl)-2-methyl-1,3-thiazole and 0.42 g of (3,3,3-cryptochromes)malononitrile was dissolved in 10 ml of N,N-dimethylformamide and then added under stirring and ice cooling 0.74 g of potassium carbonate. The mixture was additionally stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.14 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (11)).

1H-NMR (CDCl3, TMS, δ(ppm)): 2,29 is 2.33 (2H, m), 2,50-2,62 (2H, m), of 2.72 (3H, c), 3,44 (2H, c), 7,21 (1H, c)

Example 12

of 0.48 g of 2-tert-butyl-4-(chloromethyl)-1,3-thiazole and 0.45 g of (3,3,3-cryptochromes)malononitrile was dissolved in 10 ml of N,N-dimethylformamide and then added with ice cooling 0.39 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically column on the silica gel, receiving of 0.54 g of compound represented by the following formula:

(hereinafter referred to as the present compound (12)).

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.42 (9H, c), 2,30-of 2.34 (2H, m), 2,52-of 2.64 (2H, m), 3,44 (2H, c), 7,18 (1H, c)

Example of getting 13

0.56 g of 2-chloro-4-(chloromethyl)-1,3-thiazole and of 0.48 g of (3,3,3-cryptochromes)malononitrile was dissolved in 20 ml of N,N-dimethylformamide and then added with ice cooling 0.88 g of potassium carbonate. The mixture was additionally stirred at room temperature for 5 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, getting to 0.63 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (13)).

1H-NMR (CDCl3, TMS, δ(ppm)): 2,28 to 2.35 (2H, m), 2,50-2,63 (2H, m), 3,42 (2H, c), 7,31 (1H, c)

Example of getting 14

By the way, is similar to that described in example receiving 13, 0.08 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (14)) was obtained using 0.3 g of 4-(chloromethyl)-2-(propargyloxy)-1,3-is jasola, 0,29 g of (3,3,3-cryptochromes)malononitrile, 10 ml of N,N-dimethylformamide and 0.54 g of potassium carbonate.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,31-of 2.38 (2H, m)to 2.55 (1H, c), 2,46-2,61 (2H, m), 3.43 points (2H, c), free 5.01 (2H, c), of 6.75 (1H, c)

Example get 15

0.66 g of the hydrochloride of 5-(chloromethyl)-2-methyl-1,3-thiazole and of 0.60 g of (3,3,3-cryptochromes)malononitrile was dissolved in 15 ml of N,N-dimethylformamide and then added with ice cooling of 1.02 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.52 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (15)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,29 is 2.33 (2H, m), 2,50-2,60 (2H, m), is 2.74 (3H, c), a 3.50 (2H, c), a 7.62 (1H, c)

Example 16

of 0.58 g of the hydrochloride of 5-(chloromethyl)-2-ethyl-1,3-thiazole and 0.49 g of (3,3,3-cryptochromes)malononitrile was dissolved in 12 ml of N,N-dimethylformamide and then added with ice cooling of 0.83 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tributyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, gaining 0.45 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (16)).

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.41 (3H, t), 2,22-of 2.26 (2H, m), 2,49-2,61 (2H, m), 3,05 (2H, HF), 3,52 (2H, c), to 7.64 (1H, c)

Example of getting 17

of 1.41 g of the hydrochloride of 2-tert-butyl-5-(chloromethyl)-1,3-thiazole and 0.81 g of (3,3,3-cryptochromes)malononitrile was dissolved in 15 ml of N,N-dimethylformamide and then added with ice cooling to 1.38 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0,86 g of compound represented by the following formula:

(hereinafter referred to as the present compound (17)).

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.46 (9H, c), 2,22-of 2.27 (2H, m), 2,49-2,61 (2H, m), 3,52 (2H, c), to 7.64 (1H, c)

Example of getting 18

0.50 g of 2-chloro-5-(chloromethyl)-1,3-thiazole and 0.49 g of (3,3,3-thrift propyl)malononitrile was dissolved in 10 ml of N,N-dimethylformamide and then added with ice cooling of 0.83 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding a saturated aqueous solution of sodium chloride, the reaction mixture of methyl tert-butyl ether. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was recrystallized from a mixture of hexane-methyl tert-butyl ether, receiving of 0.53 g of compound represented by the following formula:

(hereinafter referred to as the present compound (18)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,20-of 2.30 (2H, m), 2,50-2,63 (2H, m), 3,49(2H, c), 7,60 (1H, c)

Example of getting 19

In nitrogen atmosphere 0.75 g {[2-(propargyloxy)-1,3-thiazol-5-yl]methyl}malononitrile and 0.82 g of 1,1,1-Cryptor-3-iodopropane was dissolved in 20 ml of N,N-dimethylformamide and of 0.60 g of potassium carbonate was then added at room temperature. The mixture was stirred at room temperature for 5 hours. After adding a saturated aqueous solution of sodium chloride, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was recrystallized from a mixture of hexane/methyl tert-butyl ether, obtaining 0.8 g of the compound, represented by the following formula:

(hereinafter referred to as the present compound (19)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,20-of 2.30 (2H, m), 2,50-to 2.65 (2H, m)2,60 (1H, c), 3,40 (2H, c), 5,07 (2H, c), 7,16 (1H, c)

Example of getting 20

By the way, is similar to that described in example 13, 0.17 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (20)) were obtained using 0.21 g of 2-(3-butenyl-1-oxy)-5-(chloromethyl)-1,3-thiazole, 0.26 g of (3,3,3-cryptochromes)malononitrile, 10 ml of N,N-dimethylformamide and 0.35 g of potassium carbonate.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,05 (1H, c), 2,20-of 2.28 (2H, m), 2,48-2,60 (2H, m), 2,70 was 2.76 (2H, m)to 3.38 (2H, c), a 4.53 (2H, t), 7,12 (1H, c)

Example of getting 21

0,76 g of the hydrochloride of 3-tert-butyl-5-(chloromethyl)-1,2,4-thiadiazole and 0.71 g of (3,3,3-cryptochromes)malononitrile was dissolved in 15 ml of N,N-dimethylformamide and then added with ice cooling 1.20 g of potassium carbonate. The mixture was stirred at room temperature for 10 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.66 g of the compound represented by the following the respective formula:

(hereinafter referred to as the present compound (21)).

1H-NMR (CDCl3, TMS, δ(ppm)): a 1.45 (9H, c), 2,44-2,48 (2H, m), 2,55-of 2.64 (2H, m), with 3.79 (2H, c)

Example of getting 22

0.87 g of 2-tert-butyl-5-(chloromethyl)-1,3,4-oxadiazole and 0,89 g of (3,3,3-cryptochromes)malononitrile was dissolved in 15 ml of N,N-dimethylformamide and then added with ice cooling to 1.38 g of potassium carbonate. The mixture was stirred at room temperature for 10 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.88 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (22)).

1H-NMR (CDCl3, TMS, δ (ppm)): a 1.45 (9H, c), 2,39 is 2.46 (2H, m), of 2.51 2.63 in (2H, m), 3,62 (2H, c)

An example of retrieving 23

of 0.57 g of 3-(chloromethyl)-5-ethyl-1,2,4-oxadiazole and 0.65 g of (3,3,3-cryptochromes)malononitrile was dissolved in 20 ml of N,N-dimethylformamide and then added with ice cooling to 0.62 g of potassium carbonate. The mixture was stirred at room temperature for 4 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. Organic the ski layer was washed with water, was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0,78 g of compound represented by the following formula:

(hereinafter referred to as the present compound (23)).

1H-NMR (CDCl3, TMS, δ (ppm): the 1.44 (3H, t), is 2.40-2.49 USD (2H, m), 2,50-2,63 (2H, m), of 2.97 (2H, HF), 3,50 (2H, c)

Example of getting 24

1.50 g of 5-tert-butyl-3-(chloromethyl)-1,2,4-oxadiazole and 1.40 g of (3,3,3-cryptochromes)malononitrile was dissolved in 50 ml of N,N-dimethylformamide and then added with ice cooling to 2.40 g of potassium carbonate. The mixture was stirred at room temperature for 4 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.88 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (24)).

1H-NMR (CDCl3, TMS, δ(ppm)): the 1.44 (9H, c), 2,40 at 2.45 (2H, m), 2,50-to 2.65 (2H, m), 3,47 (2H, c)

Example get 25

0.97 g of 5-(1-methylcyclopropyl)-3-(chloromethyl)-1,2,4-oxadiazole and 0.64 g of (3,3,3-cryptochromes)malononitrile was dissolved in 0 ml of N,N-dimethylformamide and then added with ice cooling 0,86 g of potassium carbonate. The mixture was stirred at room temperature for 4 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.33 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (25)).

1H-NMR (CDCl3, TMS, δ (ppm)): 1,09 (2H, m)to 1.45 (2H, m), of 1.57 (3H, c), 2,30 at 2.45 (2H, m), a 2.45-2.63 in (2H, m), 3,42 (2H, c)

Example of getting 26

0.21 g of 5-(2,2-dimethylpropyl)-3-(chloromethyl)-1,2,4-oxadiazole and to 0.19 g of (3,3,3-cryptochromes)malononitrile was dissolved in 10 ml of N,N-dimethylformamide and then added with ice cooling 0.17 g of potassium carbonate. The mixture was stirred at room temperature for 4 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.18 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (26)).

1H is the Mr (CDCl 3, TMS, δ(ppm)): 0,98 (9H, c), 2,29-of 2.38 (2H, m), 2,42 is 2.55 (2H, m), 2,77 (2H, c), 3,42 (2H, c)

Example of getting 27

0.71 g of 1-bromo-3,3,3-tryptophan and 0.77 g of [1-(1-tert-butyl-1H-pyrazole-4-yl)ethyl]malononitrile was dissolved in 4 ml of N,N-dimethylformamide and then added with ice cooling 0.55 g of potassium carbonate and 0.66 g of potassium iodide. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0,49 g of compound represented by the following formula:

(hereinafter referred to as the present compound (27)).

1H-NMR (CDCl3, TMS, δ(ppm): to 1.61 (9H, c)of 1.65 (3H, d), 2,04-of 2.09 (2H, m), 2,42 of $ 2.53 (2H, m)of 3.25 (1H, HF), 7,51 (1H, c), 7,55 (1H, c)

Example of getting 28

1.52 g of 2-(chloromethyl)-8-methylimidazo[1,2-a]pyridine and 1.36 g of (3,3,3-cryptochromes)malononitrile was dissolved in 20 ml of N,N-dimethylformamide and then added with ice cooling to 1.16 g of potassium carbonate. The mixture was stirred at room temperature for 7 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous sulfate is Agnes, was filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel and then recrystallized from a mixture of hexane-ethyl acetate, receiving 1.50 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (28)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,38-to 2.42 (2H, m), 2,54-of 2.66 (2H, m), to 2.57 (3H, c), 3,53 (2H, c), of 6.73 (1H, t), of 7.00 (1H, DD), 7,66 (1H, c), of 7.97 (1H, d)

An example of obtaining 29

1,67 g of 2-(chloromethyl)-5-methylimidazo[1,2-a]pyridine and 1,49 g of (3,3,3-cryptochromes)malononitrile was dissolved in 25 ml of N,N-dimethylformamide and then added with ice cooling to 2.54 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel and then recrystallized from a mixture of hexane-ethyl acetate, getting 1.92 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (29)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,37-to 2.41 (2H, m), of 2.51 2.63 in (2H, m), to 2.57 (3H, c), 3,63 (2H, c), to 6.67 (1H, DD), 7,19 (1H, DD), of 7.48 (1H, d), 7,56 (1H, c)

Example 30

2.15 g of the hydrochloride of 4-(chloromethyl)-1-cyclohexyl-1H-pyrazole and 1.50 g of (3,3,3-cryptochromes)malononitrile was dissolved in 20 ml of N,N-dimethylformamide and then added with ice cooling 2,63 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 1.98 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (30)).

1H-NMR (CDCl3, TMS, δ (ppm)): 1,24 of 1.28 (2H, m), 1,31-to 1.45 (2H, m), of 1.70 to 1.76 (2H, m), 1,88-of 1.92 (1H, m), 2,15-of 2.20 (3H, m), 2,34-is 2.37 (1H, m), 2,46-of 2.54 (3H, m), 3,19 (2H, c), 4.09 to-4,13 (1H, m), 7,51 (1H, c), 7,52 (1H, c)

An example of retrieving 31

0.73 g [(1-propargyl-1H-pyrazole-4-yl)methyl]malononitrile and 1.39 g of 1-iodine-3,3,3-tryptophan was dissolved in 4 ml of N,N-dimethylformamide and then added with ice cooling 0.55 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then what was koncentrirebuli under reduced pressure. The residue was chromatographically on a column of silica gel and then recrystallized from a mixture of hexane-ethyl acetate, gaining 0.45 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (31)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,17-2,22 (2H, m), 2,47-of 2.58 (3H, m), 3,21 (2H, c), equal to 4.97 (2H, d), 7,58 (1H, c), of 7.75 (1H, c)

Example of getting 32

0.14 g of 2-methylacrylamide and 0.30 g of 2-(1-tert-butyl-1H-pyrazole-4-ylmethyl)malononitrile was dissolved in 1 ml N,N-dimethylformamide and then added with ice cooling to 0.22 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.21 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (32)).

1H-NMR (CDCl3, TMS, δ(ppm)): was 1.58 (9H, c)to 1.59 (3H, c), 2,62 (2H, c)and 3.15 (2H, c), to 5.08 (1H, c)to 5.17 (1H, c), 7,55 (1H, c), to 7.61 (1H, c)

An example of obtaining 33

0.26 g of 3-bromocyclohexene and 0.30 g [(1-tert-butyl-1H-pyrazole-4-yl)methyl]malononitrile was dissolved in 1 ml N,N-dimethylformamide and then add the Yali under ice cooling to 0.22 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.11 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (33)).

1H-NMR (CDCl3, TMS, δ(ppm)): 1,57-of 1.64 (3H, m)to 1.59 (9H, c), 1,87-to 1.98 (1H, m), 2,04-of 2.15 (2H, m), 2,68 (1H, users.), and 3.16 (2H, c), 5,74-USD 5.76 (1H, m), 6,10-6,13 (1H, m), 7,54 (1H, c), the 7.65 (1H, c)

An example of retrieving 34

1.42 g of 4-(chloromethyl)-5-(1H-pyrrol-1-yl)-1-tert-butyl-1H-pyrazole and 0.97 g of (3,3,3-cryptochromes)malononitrile was dissolved in 12 ml of N,N-dimethylformamide and then added with ice cooling of 0.83 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 2.20 g of the compound represented by the following formula:

(hereinafter referred to the AK the present compound (34)).

1H-NMR (CDCl3, TMS, δ (ppm)): USD 1.43 (9H, c), 2,04-2,11 (2H, m), of 2.38-2.49 USD (2H, m), and 2.79 (2H, c), 6.35mm (2H, t), of 6.73 (2H, t), 7,73 (1H, c)

Example of getting 35

of 0.47 g of 3-(methyl bromide)-5-cryptomaterial and 0.32 g of (3,3,3-cryptochromes)malononitrile was dissolved in 4 ml of N,N-dimethylformamide and then added with ice cooling, and 0.28 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.36 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (35)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,29-of 2.34 (2H, m), of 2.51 2.63 in (2H, m), 3,51 (2H, c)6,91 (1H, c)

Example of getting 36

to 1.14 g of 3-(1-bromacil)-5-cryptomaterial and from 0.76 g of (3,3,3-cryptochromes)malononitrile was dissolved in 8 ml of N,N-dimethylformamide and added to stir the solution under ice cooling 0.65 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous is magnesium sulfate, was filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0,41 g of compound represented by the following formula:

(hereinafter referred to as the present compound (36)).

1H-NMR (CDCl3, TMS, δ (ppm))of 1.75 (3H, d), 2,12-of 2.20 (2H, m), of 2.51-of 2.58 (2H, m)to 3.64 (1H, HF), 6,89 (1H, c)

An example of retrieving 37

to 1.00 g of 3-(1-bromopropyl)-5-cryptomaterial and 0.62 g of (3,3,3-cryptochromes)malononitrile was dissolved in 8 ml of N,N-dimethylformamide and then added with ice cooling of 0.53 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.31 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (37)).

1H-NMR (CDCl3, TMS, δ (ppm)): 0,94 (3H, t), 1,99-2,19 (3H, m), 2,29 to 2.35 (1H, m), 2,43-2,61 (2H, m), 3,37 (1H, DD), to 6.88 (1H, c)

An example of retrieving 38

1.70 g of 3-(methyl bromide)-5-pentafluorothiophenol and 1.20 g of (3,3,3-cryptochromes)malononitrile was dissolved in 15 ml of N,N-dimethylformamide and ZAT is added under ice cooling of 1.02 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 1,71 g of compound represented by the following formula:

(hereinafter referred to as the present compound (38)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,30-of 2.34 (2H, m), 2,52-2,63 (2H, m), 3,52 (2H, c), of 6.96 (1H, c)

An example of retrieving 39

and 0.46 g of 3-(chloromethyl)-5-(heptafluoropropyl)isoxazol and 0.26 g of (3,3,3-cryptochromes)malononitrile was dissolved in 2 ml N,N-dimethylformamide and then added with ice cooling to 0.22 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.27 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (39)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,29 is 2.33 (2H, m)of 2.51 2.63 in (2H, m), 3,53 (2H, c), of 6.96 (1H, c)

Example of getting 40

of 0.44 g of (5-isopropyl-isoxazol-3-yl)methyl 4-toluensulfonate and 0.24 g of (3,3,3-cryptochromes)malononitrile was dissolved in 3 ml of N,N-dimethylformamide was added 0.25 g of potassium iodide and 0.21 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.27 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (40)).

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.33 (6H, d), 2,25-to 2.29 (2H, m), 2,49-2,60 (2H, m), is 3.08 (1H, m), 3,39 (2H, c), 6,13 (1H, c)

An example of retrieving 41

0.39 g of 3-(1-chloroethyl)-5-isopropylthiazole and 0.36 g of (3,3,3-cryptochromes)malononitrile was dissolved in 2 ml N,N-dimethylformamide and then added with ice cooling to 0.30 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure the AI. The residue was chromatographically on a column of silica gel, receiving 0.31 g of the compound represented by the formula:

(hereinafter referred to as the present compound (41)).

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.32 (6H, d), to 1.60 (3H, d), 2,07-2,17 (2H, m), 2,42-2,62 (2H, m), of 3.07 (1H, m), 3,49 (1H, HF), 6,10 (1H, c)

An example of retrieving 42

1.50 g of 3-(1-chloroethyl)-5-tert-butylisoxazole and from 0.76 g of (3,3,3-cryptochromes)malononitrile was dissolved in 5 ml of N,N-dimethylformamide and then added with ice cooling to 0.78 g of potassium iodide and 0.65 g of potassium carbonate. The mixture was additionally stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.75 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (42)).

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.37 (9H, c)to 1.60 (3H, d), 2,11-to 2.18 (2H, m), 2,44-of 2.64 (2H, m), 3,49 (1H, HF), between 6.08 (1H, c)

An example of retrieving 43

4,34 g of 3-(1-methyl bromide)-5-(tert-butyldimethylsilyloxy)isoxazol and 2.76 g (3,3,3-cryptochromes)malononitrile was dissolved in 17 ml of N,N-dimethylformamide was added p and ice cooling to 2.35 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 6.11 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (43)).

1H-NMR(CDCl3, TMS, δ (ppm)): 0,12 (6H, c)to 0.94 (9H, c), 2,24-of 2.28 (2H, m), 2,48-2,60 (2H, m), 3,42 (2H, c), to 4.81 (2H, c), 6,38 (1H, c)

An example of retrieving 44

6,40 g [(5-(tert-butyldimethylsilyloxy)isoxazol-3-yl)methyl](3,3,3-cryptochromes)malononitrile was dissolved in 50 ml of tetrahydrofuran was added under ice cooling 17 ml of a 1M solution of tetrabutylammonium fluoride in tetrahydrofuran. The mixture was stirred at room temperature for 4 hours. After adding a saturated aqueous solution of sodium bicarbonate, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 2.97 g of compound represented by the following formula:

(hereinafter referred to as the present compound (44)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,07 (1H, t), and 2.26-of 2.30 (2H, m), 2,49-2,61 (2H, m), 3.43 points (2H, c), a 4.83 (2H, d), 6,46 (1H, d)

An example of retrieving 45

0.27 g of the present compound (44) was dissolved in 1.5 ml dichloromethane and stirred with ice cooling. To the solution was added 0.18 g TRIFLUORIDE (dimethylamino)sulfur and then stirred at room temperature for 4 hours. After adding a saturated aqueous solution of sodium bicarbonate, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.20 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (45)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,28-2,31 (2H, m), 2,50-2,61 (2H, m), 3,49 (2H, c), 5,42 (2H, d), 6,60 (1H, d)

An example of retrieving 46

2,04 g {[5-(hydroxymethyl)isoxazol-3-yl]methyl}(3,3,3-cryptochromes)malononitrile was dissolved in 75 ml of 1,4-dioxane and then added 3.25 g of manganese dioxide. The mixture was stirred and heated at boiling under reflux for 6 hours. The reaction mixture was cooled to room temperature and filtered through celite® . The filtrate was concentrated under reduced pressure and the residue was chromatographically on a column of silica gel, receiving 1,17 g of compound represented by the following formula:

(hereinafter referred to as the present compound (46)).

1H-NMR (CDCl3, TMS, δ(ppm)): 2,29-of 2.34 (2H, m), of 2.51 2.63 in (2H, m), 3,51 (2H, c), 7,16 (1H, c), there is a 10.03 (1H, c)

An example of retrieving 47

0.27 g of the present compound (46) was dissolved in 5 ml dichloromethane and stirred with ice cooling. To the solution was added 0.33 g TRIFLUORIDE (dimethylamino)sulfur and then stirred at room temperature overnight. After adding a saturated aqueous solution of sodium bicarbonate, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.14 g of the compound represented by the formula:

(hereinafter referred to as the present compound (47)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,28 of-2.32 (2H, m), of 2.51-2,60 (2H, m), 3,49 (2H, c), 6,66-6,93 (2H, m)

Example obtain 48

of 3.60 g of {5-[1-(tert-butyldimethylsilyloxy)ethyl]isoxazol-3-yl}methyl-4-toluensulfonate and 1.43 g of (3,3,3-cryptochromes)malononitrile was dissolved in 10 ml of N-dimethylformamide and then added with ice cooling of 1.46 g of potassium iodide and 1.22 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 2.65 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (48)).

1H-NMR (CDCl3, TMS, δ (ppm)): 0,08 (3H, c), 0,11 (3H, c), of 0.90 (9H, c), and 1.54 (3H, d), 2,25-of 2.28 (2H, m), 2,52-2,60 (2H, m)to 3.41 (2H, c), equal to 4.97 (1H, HF), 6,32 (1H, c)

An example of retrieving 49

of 2.54 g of the present compound (48) was dissolved in 20 ml of tetrahydrofuran was added 7 ml of 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran. The mixture was stirred at room temperature for 4 hours. After adding a saturated aqueous solution of sodium bicarbonate, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 1.35 g of the compound represented by the following formula:

(hereinafter referred to as the present compounds is their (49)).

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.62 (3H, d), and 2.26-of 2.30 (2H, m), 2,49-of 2.58 (2H, m), 3,42 (2H, c), 5,04 (1H, HF), 6,40 (1H, c)

Example of getting 50

0.32 g of the present compound (49) was dissolved in 5 ml dichloromethane and stirred with ice cooling. To the solution was added 0.21 g TRIFLUORIDE (dimethylamino)sulfur and then stirred at room temperature for 4 hours. After adding a saturated aqueous solution of sodium bicarbonate, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.21 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (50)).

1H-NMR (CDCl3, TMS, δ (ppm)): 1,73-to 1.79 (3H, DD), 2,27-2,31 (2H, m), 2,50-2,61 (2H, m), 3,44 (2H, c), 5,66-of 5.83 (1H, m), 6,50 (1H, c)

An example of retrieving 51

0,99 g of the present compound (49) was dissolved in 60 ml of 1,4-dioxane and then added 2,96 g of manganese dioxide. The mixture was stirred and heated at the boil under reflux for 5 hours. The reaction mixture was cooled to room temperature and then filtered through celite®. The filtrate was concentrated under reduced pressure and the residue of chromatography the Wali on a column of silica gel, getting to 0.67 g of compound represented by the following formula:

(hereinafter referred to as the present compound (51)).

1H-NMR (CDCl3, TMS, δ (ppm)): 2,29 of-2.32 (2H, m), of 2.54 2.63 in (2H, m), 2,65 (3H, c), a 3.50 (2H, c), 7,06 (1H, c)

An example of retrieving 52

1.10 g of 3-(chloromethyl)-5-(1,1-dottorati)isoxazol and 1.00 g of (3,3,3-cryptochromes)malononitrile was dissolved in 12 ml of N,N-dimethylformamide and then added with ice cooling 0.84 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving and 0.98 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (52)).

1H-NMR (CDCl3, TMS, δ (ppm)): a 2.01 (3H, t), 2,22 is 2.33 (2H, m), of 2.51-2,62 (2H, m), 3,44 (2H, c), 6,63 (1H, c)

Example of getting 53

0,41 g {[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile and 1.00 g of 1-iodine-3,3,3-tryptophan was dissolved in 6 ml N,N-dimethylformamide and then added with ice cooling 0.55 g of potassium carbonate. The mixture was stirred at room temperature overnight. PEFC is adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving and 0.46 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (53)).

1H-NMR (CDCl3, TMS, δ (ppm)): 1,68 (6H, c), 2,27-2,31 (2H, m), 2,49-2,61 (2H, m)to 3.41 (2H, c), 6.35mm (1H, c)

An example of retrieving 54

0.36 g of the present compound (53) was dissolved in 5 ml dichloromethane was added under ice cooling 0.24 g TRIFLUORIDE (dimethylamino)sulfur. The mixture was stirred at room temperature for 4 hours. After adding a saturated aqueous solution of sodium bicarbonate, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.27 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (54)).

1H-NMR (CDCl3, TMS, δ (ppm)): 1,76 (6H, d), 2,28 of-2.32 (2H, m), 2,50-2,62 (2H, m), 3.43 points (2H, c), to 6.43 (1H, c)

Example of getting 55

0,41 g {[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile and 0.57 is iodotope bromide was dissolved in 6 ml N,N-dimethylformamide and then added with ice cooling 0.55 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.31 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (55)).

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.62 (6H, c)to 1.87 (3H, c), the 3.35 (2H, c), 6.35mm (1H, c)

An example of receiving 56

0,41 g {[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile and 0.66 g iodine ethyl was dissolved in 6 ml N,N-dimethylformamide and then added with ice cooling 0.55 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, getting 0.32 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (56)).

1H-NMR (CDCl3, TMS, δ (ppm)): 1,31 (3H, t), of 1.65 (6H, c)to 2.06 (2H, HF), to 3.34 (2H, c), 6,36 (1H, c)

An example of retrieving 57

0,41 g {[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile and 0.73 g of 1-iodopropane was dissolved in 6 ml N,N-dimethylformamide and then added with ice cooling 0.55 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 0.30 g of compound represented by the following formula:

(hereinafter referred to as the present compound (57)).

1H-NMR (CDCl3, TMS, δ (ppm)): the 1.04 (3H, t), and 1.63 (6H, c), 1,71-of 1.81 (2H, m), 1,94-1,19 (2H, m)to 3.34 (2H, c), 6,36 (1H, c)

An example of retrieving 58

0,41 g {[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile and 0.81 g of 1-iodobutane was dissolved in 6 ml N,N-dimethylformamide and then added with ice cooling 0.55 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure, the NII. The residue was chromatographically on a column of silica gel, receiving 0.31 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (58)).

1H-NMR (CDCl3, TMS, δ (ppm)): 0,94 (3H, t), 1,39-1,49 (2H, m), and 1.63 (6H, c), 1,61-of 1.74 (2H, m), 1,89 of 1.99(2H, m)to 3.34 (2H, c), 6,36 (1H, c)

Example retrieve 59

0,41 g {[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile and 0.88 g of 1-iodine-3-methylbutane was dissolved in 6 ml N,N-dimethylformamide and then added with ice cooling 0.55 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.31 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (59)).

1H-NMR (CDCl3, TMS, δ (ppm)): of 0.95 (6H, d), 1,53 was 1.69 (2H, m), of 1.65 (6H, c), 1,90-of 1.94 (2H, m), 1,97-2,04 (2H, m)to 3.34 (2H, c), 6,36 (1H, c)

Example of getting 60

0,41 g {[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile and 0.63 g of allyl chloride was dissolved in 6 ml N,N-dimethylformamide and then added while cooling LDO is 0.55 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with ethyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.33 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (60)).

1H-NMR (CDCl3, TMS, δ (ppm)): 1,65 (6H, c), 2,68 (2H, d), to 3.34 (2H, c), 5,39-the 5.51 (2H, m), 5,85 of 5.99 (1H, m), 6,36 (1H, c)

An example of retrieving 61

0,41 g {[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile and 0.63 g of 4-iodine-1-butene dissolved in 6 ml N,N-dimethylformamide and then added with ice cooling 0.55 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 0.43 g (3-butenyl){[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile, represented by the following formula:

(hereinafter referred to the AK the present compound (61)).

1H-NMR (CDCl3, TMS, δ (ppm)): 1,65 (6H, c), 2,02-to 2.18 (2H, m), 2,43-2,52 (2H, m)to 3.36 (2H, c), 5,11-to 5.21 (2H, m), 5,78-to 5.85 (1H, m), 6,36 (1H, c)

An example of retrieving 62

0,41 g {1-[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]ethyl}malononitrile and 1.00 g of 1-iodine-3,3,3-tryptophan was dissolved in 6 ml N,N-dimethylformamide and then added with ice cooling 0.55 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving the compound represented by the following formula:

(hereinafter referred to as the present compound (62)).

1H-NMR (CDCl3, TMS, δ (ppm)): 1,64 (3H, c), of 1.66 (3H, c), 1,71 (3H, d), 2,08-of 2.20 (2H, m), 2,41-to 2.65 (2H, m)to 3.41 (1H, HF), 6,33 (1H, c)

An example of retrieving 63

0,41 g {1-[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]ethyl}malononitrile and 0.82 g of allyl chloride was dissolved in 6 ml N,N-dimethylformamide and then added with ice cooling 0.55 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed water is, was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 0.44 g of compound represented by the following formula:

(hereinafter referred to as the present compound (63)).

1H-NMR(CDCl3, TMS, δ (ppm)): 1,65 (6H, c)to 1.67 (3H, d), of 2.23 (1H, users), 2,55-to 2.57 (2H, m), 3,53 (1H, HF), 5,39-5,46 (2H, m), 5,86-5,97 (1H, m), 6,34 (1H, c)

Example of getting 64

0.40 g of {1-[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]propyl}malononitrile and 0.43 g of 1-iodine-3,3,3-tryptophan was dissolved in 5 ml of N,N-dimethylformamide and then added with ice cooling 0.25 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving and 0.37 g of compound represented by the following formula:

(hereinafter referred to as the present compound (64)).

1H-NMR (CDCl3, TMS, δ (ppm)): to 0.92 (3H, t), of 1.66 (6H, c), 1,99-of 2.28 (4H, m), 2,42-2,60 (2H, m), 3,24 of 3.28 (1H, m), 6,32 (1H, c)

Example getting 65

0.40 g of {1-[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]-2-ethylpropyl}malononitrile and 0.40 g of 1-iodine-3,3,3-tryptophan was dissolved in 5 ml of N,N-dimethylformamide and then added with ice cooling 0.25 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.33 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (65)).

1H-NMR (CDCl3, TMS, δ(ppm)): a 1.08 (3H, d), of 1.18 (3H, d), of 1.66 (6H, c), 1,93-2,11 (2H, m), 2.40 a-2,63 (3H, m), 3,21 (1H, d), 6,34 (1H, c)

An example of retrieving 66

0.56 g of {1-[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]-2-propenyl}malononitrile and of 0.58 g of 1-iodine-3,3,3-tryptophan was dissolved in 5 ml of N,N-dimethylformamide and then added with ice cooling 0.35 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving and 0.46 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (66)).

p> 1H-NMR (CDCl3, TMS, δ(ppm)): 1,65 (6H, c), and 2.14 of-2.32 (2H, m), a 2.45-2.63 in (2H, m), 3,98 (1H, d), 5,54-5,63 (2H, m), 6,07-x 6.15 (1H, m), 6,33 (1H, c)

An example of retrieving 67

0.21 g of 3-(chloromethyl)-5-[1-methyl-1-(2-propenyloxy)ethyl]isoxazol and 0.16 g of (3,3,3 cryptochromes)malononitrile was dissolved in 2 ml of N,N dimethylformamide was added under ice cooling 0.14 g of potassium carbonate and 0.17 g of potassium iodide. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.16 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (67)).

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.66 (6H, c), 2,28-2,31 (2H, m), 2,39 (1H, t), 2,50-2,61 (2H, m), 3,42(2H, c), of 4.05 (2H, d), 6,40 (1H, c)

Example of getting 68

0.96 g of 5-(chloromethyl)-3-methoxyethanol and 1.05 g of (3,3,3-cryptochromes)malononitrile was dissolved in 13 ml of N,N-dimethylformamide was added under ice cooling of 0.90 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed water is, was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 1.05 g of compound represented by the following formula:

(hereinafter referred to as the present compound (68)).

1H-NMR (CDCl3, TMS, δ(ppm)): 2,25-of 2.36 (2H, m), 2,48-2,60 (2H, m)to 3.41 (2H, c), of 3.96 (3H, c), 6,10 (1H, c)

Example of getting 69

0.96 g of [(2-ethylthio-1-Mei-5-yl)methyl]malononitrile and of 0.91 g of 1-iodine-3,3,3-tryptophan was dissolved in 15 ml of N,N-dimethylformamide and then added with ice cooling to 0.60 g of potassium carbonate. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.39 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (69)).

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.32 (3H, t), 2,25-of 2.30 (2H, m), 2,48-2,60 (2H, m), 3,10 (2H, HF), to 3.33 (2H, c), 3,62 (3H, c), 7,19 (1H, c)

Example of getting 70

0.21 g of the present compound (69) was dissolved in 5 ml of chloroform and then added in the OHL is the establishment of ice 0.14 g m-chloroperbenzoic acid. The mixture was stirred at room temperature overnight. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.21 g of the compound represented by the following formula:

(hereinafter referred to as the present compound (70)).

1H-NMR (CDCl3, TMS, δ(ppm)): 1,36-of 1.56 (3H, m), is 2.30 to 2.35 (2H, m), of 2.51 2.63 in (2H, m), 3,37 is 3.57 (2H, m)to 3.33 (2H, c), of 4.00 (3H, c), 7,33 (1H, c)

Further, in the reference examples of the preparation will be described the production of intermediate products for the synthesis of these compounds.

Reference example obtain 1

Hydrochloride 3-tert-butyl-5-(chloromethyl)-1H-pyrazole

The above compound was obtained by the method described in J.Org.Chem.,67,9200 (2002).

1H-NMR (CDCl3, TMS, δ(ppm)): to 1.47 (9H, c), 4,78 (2H, c), 6.42 per (1H, c)

Reference example getting 2

Hydrochloride 3-tert-butyl-5-(chloromethyl)-1-methyl-1H-pyrazole

The above compound was synthesized by a method similar to that described in reference example get 1.

1H-NMR (CDCl3, TMS, δ(ppm)): to 1.48 (9H, c)to 4.33 (3H, c), br4.61 (2H, c), 6,37 (1H, c)

SS is loony example of getting 3

Hydrochloride 3-tert-butyl-5-(chloromethyl)-1-(2,2,2-trifluoromethyl)-1H-pyrazole

The above compound was synthesized by a method similar to that described in reference example get 1.

1H-NMR (CDCl3, TMS, δ(ppm)): to 1.38 (9H, c), of 4.54 (2H, c), 4,74 (2H, HF), 6,16 (1H, c)

Reference example obtaining 4-1

(3-tert-Butyl-isoxazol-5-yl)methanol

The above compound can be obtained from 2,2-dimethyl-6-(tetrahydro-2H-Piran-2-yloxy)-4-hexyne-3-one, which is obtained by the method described in J.Org.Chem., 67, 9200 (2002), by the following method.

of 4.49 g of 2,2-dimethyl-6-(tetrahydro-2H-Piran-2-yloxy)-4-hexyne-3-one was dissolved in 20 ml of methanol, and added to 1.30 g of sodium methoxide and 1.53 g of hydroxylamine hydrochloride. The mixture was stirred at 70°C for 2 hours. The reaction mixture was cooled to room temperature and then brought to pH 2 using concentrated hydrochloric acid. The mixture was stirred at room temperature for 18 hours. After adding a saturated aqueous solution of sodium bicarbonate, the reaction mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was chromatographically on the column with silicagel is m, receiving 1.12 g (3-tert-butyl-isoxazol-5-yl)methanol.

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.33 (9H, c), 4,74 (2H, c), 6,16 (1H, c)

Reference example obtaining 4-2

3-tert-Butyl-5-(chloromethyl)isoxazol

1.12 g (3-tert-butyl-isoxazol-5-yl)methanol was dissolved in 35 ml of dichloromethane and was added 2.4 ml of chloride tiomila. The mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was washed with hexane, receiving 1.12 g of 3-tert-butyl-5-(chloromethyl)-isoxazol.

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.34 (9H, c), 4,58 (2H, c), from 6.22 (1H, c)

Reference example obtaining 5-1

(3-tert-Butyl-isothiazol-5-yl)methanol

The above compound was obtained by the method described in Heterocycles, 27, 97, (1989).

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.34 (9H, c), 2,33 (1H, users), 4,72 (2H, c), 6,00 (1H, c)

Reference example obtaining 5-2

3-tert-Butyl-5-(chloromethyl)isothiazol

of 1.61 g of (3-tert-butyl-isothiazol-5-yl)methanol was dissolved in 50 ml of dichloromethane and was added 3.2 ml of chloride tiomila. The mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, obtaining 1.12 g of 3-tert-butyl-5-(chloromethyl)isothiazole. The crude product was introduced in the following study is without purification.

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.36 (9H, c)4,55 (2H, c), equal to 6.05 (1H, c)

Reference example obtaining 6-1

Ethyl 5-tert-butyl-isoxazol-3-carboxylate

5,61 g of tert-butylaniline and of 9.09 g of ethyl (2E)-chlorine(hydroxyimino)acetate was dissolved in 70 ml of tetrahydrofuran and then added dropwise at 0°C within 30 minutes of 11.4 ml of triethylamine. The mixture was stirred at room temperature overnight. After adding a saturated aqueous solution of sodium chloride, the reaction mixture was separated into layers. The aqueous layer was extracted with methyl tert-butyl ether. The organic layers were combined, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, getting to 1.83 g of ethyl 5-tert-butyl-isoxazol-3-carboxylate.

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.37 (9H, c)of 1.39 (3H, t), and 4.40 (2H, q), 6,37 (1H, c)

Reference example obtaining 6-2

(5-tert-Butyl-isoxazol-3-yl)methanol

to 1.83 g of ethyl 5-tert-butyl-isoxazol-5-carboxylate was dissolved in 18 ml of tetrahydrofuran, and then added to 0.70 g of sodium borohydride in 10 ml of ethanol. The mixture was stirred at room temperature for 10 hours. After adding 5 ml of water the reaction mixture was concentrated to a volume of 5 ml under reduced gallerian solution was extracted with methyl tert-butyl ether. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure, obtaining of 0.62 g of (5-tert-butyl-isoxazol-3-yl)methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.35 (9H, c), of 1.94 (1H, users), 4,72 (2H, d), 6,00 (1H, c)

Reference example obtaining 6-3

5-tert-Butyl-3-(chloromethyl)isoxazol

of 0.62 g of (5-tert-butyl-isoxazol-3-yl)methanol was dissolved in 12 ml of dichloromethane and was added to 0.9 ml of chloride tiomila. The mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, getting to 0.69 g of 5-tert-butyl-3-(chloromethyl)isoxazol.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.34 (9H, c)4,55 (2H, c), equal to 6.05 (1H, c)

Reference example obtaining 7-1

Methyl 1-tert-butyl-1H-pyrazole-4-carboxylate

8,51 g of sodium salt of methyl 2-(dimethoxymethyl)-3-hydroxyacrylates suspended in 80 ml of ethanol and then added of 8.09 g of the hydrochloride tert-butylhydrazine. The mixture was stirred at 60°C for 4 hours and then cooled to room temperature. After adding 50 ml of water the reaction mixture was concentrated to a volume of 50 ml under reduced pressure. The concentrated solution was extracted with ethyl acetate. The organic layer was washed saturated aqueous sodium chloride, dried over besttranslator sodium and then concentrated under reduced pressure. The residue was recrystallized from hexane, receiving of 5.26 g of methyl 1-tert-butyl-pyrazole-4-carboxylate.

1H-NMR(CDCl3, TMS, δ(ppm)): of 1.62 (9H,c)a 3.83 (3H, c), to 7.93 (1H, c), 8,02 (1H, c)

Reference example obtaining 7-2

(1-tert-Butyl-1H-pyrazole-4-yl)methanol

In the atmosphere of nitrogen added to 1.25 g socialwise hydride in 100 ml of tetrahydrofuran, and added dropwise at 0°C for 30 minutes the solution 5,01 g of methyl 1-tert-butyl-1H-pyrazole-4-carboxylate in 50 ml of tetrahydrofuran. Then the mixture was stirred at room temperature for 7 hours. The reaction mixture was cooled to 0°C and then added dropwise 10 ml of 1 mol/l aqueous solution of potassium hydroxide. The precipitate was filtered and washed with tetrahydrofuran. The filtrate was concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving as 4.02 g (1-tert-butyl-1H-pyrazole-4-yl)methanol.

1H-NMR (CDCl3, TMS, δ(ppm)): was 1.58 (9H, c), 4,59 (2H, d), 7,53 (1H, c), 7,54 (1H, c)

Reference example obtaining 7-3

Hydrochloride of 1-tert-butyl-4-(chloromethyl)-1H-pyrazole

of 0.77 g (1-tert-butyl-1H-pyrazole-4-yl)methanol was dissolved in 25 ml of dichloromethane and was added 1.7 ml of chloride tiomila. The mixture was stirred at room temperature for 5 hours. Then the reaction mixture conc is listed under reduced pressure, receiving 1.12 g of the hydrochloride of 1-tert-butyl-4-(chloromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,50 (9H, c), 4,69 (2H, c), 7,51 (1H, c), 7,94 (1H, c)

Reference example receive 8-1

Methyl 1-benzyl-1H-pyrazole-4-carboxylate

18,68 g of sodium salt of methyl 2-(dimethoxymethyl)-3-hydroxyacrylates was added to 80 ml of ethanol and added 18,39 g of the dihydrochloride of benzylpiperazine. The mixture was stirred at 70°C for 7 hours and then cooled to room temperature. After adding 100 ml of water and the mixture was concentrated to 100 ml under reduced pressure. The concentrated solution was extracted with ethyl acetate. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 7,39 g of methyl 1-benzyl-1H-pyrazole-4-carboxylate.

1H-NMR (CDCl3, TMS, δ(ppm)): is 3.08 (3H, c), and 5.30 (2H, c), 7.23 percent-7,39 (5H, m), a 7.85 (1H, c), 7,94 (1H, c)

Reference example obtaining 8-2

(1-Benzyl-1H-pyrazole-4-yl)methanol

In nitrogen atmosphere 1.44 g socialwise hydride was added to 100 ml of tetrahydrofuran and added dropwise at 0°C for 30 minutes the solution 7,39 g of methyl 1-benzyl-1H-pyrazole-4-carboxylate in 50 ml of tetrahydrofuran. The mixture is then paramashiva and at room temperature for 5 hours. The reaction mixture was cooled to 0°C and added dropwise 15 ml of 1 mol/l aqueous solution of potassium hydroxide. The precipitate was filtered, washed with tetrahydrofuran and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 6,32 g (1-benzyl-1H-pyrazole-4-yl)methanol.

1H-NMR (CDCl3, TMS, δ(ppm)): 4,56 (2H, c), 5,27 (2H, c), 7,21-of 7.25 (2H, m), 7,28-7,37 (4H, m), 7,53 (1H, c)

Reference example get 8-3

Hydrochloride of 1-benzyl-4-(chloromethyl)-1H-pyrazole

1.88 g (1-benzyl-1H-pyrazole-4-yl)methanol was dissolved in 30 ml of dichloromethane and was added to 2.1 ml of chloride tiomila. The mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, getting 2,39 g of the hydrochloride of 1-benzyl-4-(chloromethyl)-1H-pyrazole.

Reference example obtain 9

4-Chloromethyl-2-tert-butyl-1,3-oxazol

The above compound was obtained by a method described in international patent publication WO97/40009.

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.41 (9H, c), 4,50 (2H, c), 7,55 (1H, c)

Reference example 10

4-(Chloromethyl)-2-methyl-1,3-thiazole

The above compound was obtained by a method described in the published German patent DE19848306.

Reference example recip is of 11

4-(Chloromethyl)-2-tert-butyl-1,3-oxazol

The above compound was obtained in a manner analogous to described the publication of German patent DE19848306.

1H-NMR (CDCl3, TMS, δ (ppm)): the 1.44 (9H, c), and 4.68 (2H, c), 7,16 (1H, c)

Reference example obtaining 12-1

Ethyl 2-chloro-1,3-thiazole-4-carboxylate

The above compound can be obtained by the following procedure from ethyl 2-amino-1,3-thiazole-4-carboxylate obtained by the method described in J.Heterocyclic.Chem., 26, 1643 (1989).

15.0 g of ethyl 2-amino-1,3-thiazole-4-carboxylate was added to 400 ml of water was then added to 500 g of concentrated sulfuric acid, 29,2 g of copper sulfate and 23.0 g of sodium chloride. The mixture was cooled to -10°C. was Added thereto dropwise a solution of 14.8 g of sodium nitrite in 55 ml of water while maintaining the internal temperature at 0°C or below. After completion of addition, the mixture was stirred at 0°C for 30 minutes and heated until the internal temperature is equal to room temperature and then further stirred for 30 minutes. The reaction mixture was extracted with ethyl acetate. The organic layer is washed with 30% aqueous ammonia solution, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The obtained residue was chromatographically on a column of silica gel, receiving 9,0g ethyl 2-chloro-1,3-thiazole-4-carboxylate.

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.41 (3H, t), 4,42 (2H, HF), 8,08 (1H, c)

Reference example get 12-2

Ethyl 2-(2-propenyloxy)-1,3-thiazole-4-carboxylate

0.20 g propargilovyh alcohol was dissolved in 20 ml of tetrahydrofuran was added at room temperature of 0.13 g of 60% sodium hydride. The mixture was stirred at room temperature for 1 hour. After addition of 0.50 g of ethyl 2-chloro-1,3-thiazole-4-carboxylate, the reaction mixture was stirred at room temperature for 3 hours. After adding a saturated aqueous solution of ammonium chloride, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.33 g of ethyl 2-(2-propenyloxy)-1,3-thiazole-4-carboxylate.

1H-NMR(CDCl3, TMS, δ(ppm)): to 1.38 (3H, t), 2,61 (1H, c), to 4.38 (2H, q), 5,14 (2H, c), a 7.62 (1H, c)

Reference example get 12-3

[2-(2-Propenyloxy)thiazol-4-yl]methanol

In nitrogen atmosphere of 0.30 g of ethyl 2-(2-propenyloxy)-1,3-thiazole-4-carboxylate was dissolved in 10 ml of tetrahydrofuran and added dropwise at 0°C to 3.3 ml of a solution (1 mol/l) hydride diisobutylaluminum in toluene. The mixture is stirred at 0° C for 1 hour. The reaction mixture was added to saturated aqueous solution of sodium chloride and then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure, getting 0,22 g [2-(2-propenyloxy)-thiazol-4-yl]methanol.

1H-NMR (CDCl3, TMS, δ(ppm)): to 2.06 (1H, users), to 2.57 (1H, c), of 4.57 (2H, d), of 5.03 (2H, c), 6,59 (1H, c)

Reference example obtaining 12-4

4-(Chloromethyl)-2-(2-propenyloxy)-thiazole

0.20 g of [2-(2-propenyloxy)thiazol-4-yl]methanol was dissolved in 5 ml of chloroform, was added 0.2 g of chloride tiomila. The mixture was heated at the boil under reflux for 1 hour. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure, obtaining of 0.30 g of 4-(chloromethyl)-2-(2-propenyloxy)thiazole.

Reference example get 13

Hydrochloride 5-(chloromethyl)-2-methyl-1,3-thiadiazole

The above compound was obtained in accordance with the method described in laid open patent publication Japan No. 2001-58979.

1H-NMR (CDCl3, TMS, δ (ppm)): 3.15 in (3H, c), a 4.83 (2H, c), with 8.05 (1H, c)

Reference example get 14

Hydrochloride 5-(chloromethyl)-2-methyl-1,3-thiadiazole

The above compound was obtained with the availa able scientific C of the way, described in laid open patent publication Japan No. 2001-58979.

1H-NMR (CDCl3, TMS, δ(ppm)): and 1.54 (3H, t), of 3.45 (2H, HF), to 4.81 (2H, c), 8,01 (1H, c)

Reference example get 15

Hydrochloride 5-(chloromethyl)-2-tert-butyl-1,3-thiadiazole

The above compound was obtained in accordance with the method described in laid open patent publication Japan No. 2001-58979.

1H-NMR (CDCl3, TMS, δ(ppm)): 1,64 (9H, c)4,80 (2H, c), is 6.61 (1H, user. c)8,01 (1H, c)

Reference example obtaining 16-1

2-Chloro-1,3-thiazole-5-carbaldehyde

The above compound was obtained in accordance with the method described in J.Chem.Soc.Perkin Trans.1,329(1990).

Reference example get 16-2

2-(2-Propenyloxy)-1,3-thiazole-5-carbaldehyde

0,37 g propargilovyh alcohol was dissolved in 100 ml of tetrahydrofuran was added in portions 0.9 g of 60% sodium hydride. The mixture was stirred at room temperature for 1 hour. Then to the reaction mixture were added 3.0 g of 2-chloro-1,3-thiazole-5-carbaldehyde and the mixture was stirred at room temperature for 3 hours. After adding a saturated aqueous solution of ammonium chloride, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with a saturated aqueous solution of chloride n is sodium, was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 1.44 g of 2-(2-propenyloxy)-1,3-thiazole-5-carbaldehyde.

1H-NMR(CDCl3, TMS, δ(ppm)): 2,64 (1H, c)to 5.13 (2H, c), 7,87 (1H, c), 9,84 (1H, c)

Reference example get 16-3

{[2-(2-Propenyloxy)-1,3-thiazol-5-yl]methyl}malononitrile

1.4 g of 2-(2-propenyloxy)-1,3-thiazole-5-carbaldehyde was dissolved in a mixture of 6 ml of water and 14 ml of ethanol and added dropwise 0.56 g of malononitrile. The mixture was stirred at room temperature for 3 hours. Then the reaction mixture was filtered and the obtained filter cake was washed twice with 5 ml of ethanol and dried under reduced pressure, obtaining 1.55 g {[2-(2-propenyloxy)-1,3-thiazol-5-yl]methylidene}malononitrile.

Then the obtained {[2-(2-propenyloxy)-1,3-thiazol-5-yl]methylidene}malononitrile was dissolved in 20 ml of ethanol and added dropwise to the suspension and 0.09 g of sodium borohydride in 1 ml of ethanol. The mixture was stirred at room temperature for 1 hour. After adding 10 ml of 3% hydrochloric acid, the reaction mixture was exteremely with ethyl acetate. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure, obtaining 1.55 g {[2-(2-propenyloxy)-1,thiazol-5-yl]methyl}.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,61 (1H, c), 3,39 (2H, d), of 3.94 (1H, t), 5,04 (2H, c), 7,13 (1H, c)

Reference example get 17-1

Methyl 3-tert-butyl-1,2,4-thiadiazole-5-carboxylate

The above compound was obtained by a method described in the publication of International patent WO 01/055136.

1H-NMR (CDCl3, TMS, δ (ppm)): is 1.51 (9H, c), was 4.02 (3H, c)

Reference example get 17-2

(3-tert-Butyl-1,2,4-thiadiazole-5-yl)methanol

0.96 g of methyl 3-tert-butyl-1,2,4-thiadiazole-5-carboxylate was dissolved in 48 ml of dichloromethane and then cooled to -78°C in nitrogen atmosphere. To the solution was added 11 ml of a solution (1 mol/l) diisopropylaminoethyl in toluene and the mixture was stirred at 0°C for 3 hours. After adding 10 ml of 1 mol/l hydrochloric acid, the reaction mixture was stirred for 10 minutes and then added 50 ml of a saturated aqueous solution of sodium bicarbonate. The reaction mixture was extracted with chlorform, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.56 g (3-tert-butyl-1,2,4-thiadiazole-5-yl)methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): USD 1.43 (9H, c), 5,09 (2H, c)

Reference example get 17-3

Hydrochloride 3-tert-butyl-5-(chloromethyl)-1,2,4-thiadiazole

0.71 g of 3-tert-butyl-5-hydroxymethyl-1,2,4-thiadiazole was dissolved in 20 ml of dichloromethane and was added to 1.4 ml of chloride tiomila. The mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure, getting 0,76 g of the hydrochloride of 3-tert-butyl-5-(chloromethyl)-1,2,4-thiadiazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.42 (9H, c), 4,91 (2H, c)

Reference example get 18-1

N'-(Chloroacetyl)-2,2-dimethylpropanamide

In nitrogen atmosphere 2.86 g of 2,2-dimethylpropanamide was dissolved in tetrahydrofuran and then added at 0°C 2,78 g chloroacetanilide. The mixture was stirred at room temperature for 18 hours. After adding a saturated aqueous solution of sodium bicarbonate, the reaction mixture was extracted with ethyl acetate. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure, getting 2.58 g of N'-(chloroacetyl)-2,2-dimethylpropanamide.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.27 (9H, c), of 4.77 (2H, c), 8,58 (1H, users), of 9.55 (1H, users)

Reference example get 18-2

2-tert-Butyl-5-(chloromethyl)-1,3,4-oxadiazol

A mixture of 1.34 g of N'-(chloroacetyl)-2,2-dimethylpropanamide and 6.6 g of polyphosphoric acid p is remedial at 90° C for 10 hours. The reaction mixture was cooled to room temperature. After adding 200 ml of water and then sodium bicarbonate, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate and then concentrated under reduced pressure, obtaining 1.12 g of 2-tert-butyl-5-(chloromethyl)-1,3,4-oxadiazol.

1H-NMR(CDCl3, TMS, δ(ppm)): to 1.47(9H, c), and 4.68(2H, c)

Reference example get 19-1

2-Chloro-N-hydroxyacetamido

The above compound was obtained by the method described in U.S. patent US 3956498,

1H-NMR (CDCl3, TMS, δ (ppm)): of 4.05 (2H, c), 4,79 (2H, users)

Reference example get 19-2

3-(Chloromethyl)-5-tert-butyl-1,2,4-oxadiazol

5.0 g of 2-chloro-N-hydroxyacetanilide and 6.11 g of trimethylacetylchloride was dissolved in 100 ml of N,N-dimethylformamide and then added dropwise with ice cooling 5.6 g of triethylamine. After completion of addition, the reaction mixture was stirred at 130°C for 6 hours and then cooled to room temperature. After adding a saturated aqueous solution of sodium chloride, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous with what LifeCam sodium and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 7.0 g of 3-(chloromethyl)-5-tert-butyl-1,2,4-oxadiazole.

1H-NMR(CDCl3, TMS, δ(ppm)): a 1.45 (9H, c), 4,56 (2H, c)

Reference example receive 20

3-(Chloromethyl)-5-(1-methylcyclopropyl)-1,2,4-oxadiazol

of 2.75 g of 2-chloro-N-hydroxyacetanilide and 3.0 g of 1-methylcyclopropene was dissolved in 50 ml of N,N-dimethylformamide was added dropwise under ice cooling 2.8 g of triethylamine. After completion of addition, the reaction mixture was stirred at 130°C for 6 hours and then cooled to room temperature. After adding a saturated aqueous solution of sodium chloride, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.97 g of 3-(chloromethyl)-5-(1-methylcyclopropyl)-1,2,4-oxadiazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,01 was 1.06 (2H, m), USD 1.43 to 1.47 (2H, m), 1,58 (3H, c), of 4.54 (2H, c)

Reference example get 21

3-(Chloromethyl)-5-ethyl-1,2,4-oxadiazol

2.0 g of 2-chloro-N-hydroxyacetanilide and of 1.80 g of chloride propionyl was dissolved in 50 ml of N,N-dimethylformamide and was added to ply under ice cooling of 2.05 g of triethylamine. The mixture was stirred at 130°C for 5 hours and then cooled to room temperature. After adding a saturated aqueous solution of sodium chloride, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving and 0.62 g of 3-(chloromethyl)-5-ethyl-1,2,4-oxadiazole.

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.42 (3H, t), of 2.92 (2H, HF), 4,59 (2H, c)

Reference example get 22

3-(Chloromethyl)-5-(2,2-dimethylpropyl)-1,2,4-oxadiazol

2.0 g of 2-chloro-N-hydroxyacetanilide and 2.6 g of 3,3-dimethylbutyramide was dissolved in 30 ml of N,N-dimethylformamide was added dropwise under ice cooling of 2.05 g of triethylamine. After completion of addition, the mixture was stirred at 130°C for 5 hours and then cooled to room temperature. After adding a saturated aqueous solution of sodium chloride, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 028 g of 3-(chloromethyl)-5-(2,2-dimethylpropyl)-1,2,4-oxadiazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.05 (9H, c), 2,82 (2H, c), 4,60 (2H, c)

Reference example receiving 23

2-(Chloromethyl)-8-methylimidazo[1,2-a]pyridine

3,81 g of 1,3-dichloroacetone or 3.24 g of 2-amino-3-methylpyridine was dissolved in 30 ml of ethanol and the solution was heated at the boil under reflux for 5 hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. To the residue was added 50 ml of a saturated aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel and then recrystallized from a mixture of hexane-methyl tert-butyl ether, receiving 1.52 g of 2-(chloromethyl)-8-methylimidazo[1,2-a]pyridine.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,60 (3H, c), 4,80 (2H, c), of 6.68 (1H, t), of 6.96 (1H, DD), to 7.61 (1H, c), to 7.93 (1H, d)

Reference example get 24

2-(Chloromethyl)-5-methylimidazo[1,2-a]pyridine

3,81 g of 1,3-dichloroacetone or 3.24 g of 2-amino-6-methylpyridine was dissolved in 30 ml of ethanol and the solution was heated at the boil under reflux for 5 hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. After you add the effect to 50 ml of a saturated aqueous solution of sodium bicarbonate residue was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel and then recrystallized from a mixture of hexane-ethyl acetate, receiving a rate of 1.67 g of 2-(chloromethyl)-5-methylimidazo[1,2-a]pyridine.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,58 (3H, c), 4,80 (2H, c), 6,62 (1H, DD), to 7.15 (1H, DD), 7,47 (1H, d), 7,52 (1H, c)

Reference example obtaining 25-1

Methyl 1-cyclohexyl-1H-pyrazole-4-carboxylate

of 3.96 g of sodium salt of methyl 2-(dimethoxymethyl)-3-hydroxyacrylates suspended in 40 ml of ethanol and was added 3.13 g of the hydrochloride of cyclohexylpiperazine. The mixture was stirred at 60°C for 4 hours and then cooled to room temperature. After adding 50 ml of water the reaction mixture was concentrated to a volume of 50 ml under reduced pressure. The concentrated solution was extracted with ethyl acetate. The organic layer was washed saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving a 3.01 g of methyl 1-cyclohexyl-1H-pyrazole-4-carboxylate.

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.21 to 1.31 (1H, m), of 1.37 to 1.48 (2H, m), 1,61-to 1.77 (4H, m), 1,89-of 1.92 (2H, c), 2,15-2,19 (2H, m), 3,82 (3H, c), 7,89 (1H, c), to $ 7.91 (1H, c)

Reference example obtaining 2-2

(1-Cyclohexyl-1H-pyrazole-4-yl)methanol

In nitrogen atmosphere 0,57 g sociallyengaged suspended in 100 ml of dry tetrahydrofuran, was added thereto dropwise over 15 minutes with stirring at 0°C solution a 3.01 g of methyl 1-cyclohexyl-1H-pyrazole-4-carboxylate in 40 ml of tetrahydrofuran. After completion of addition, the mixture was stirred at room temperature for 7 hours and then cooled to 0°C. thereto was added dropwise 10 ml of 1 mol/l of a saturated aqueous solution of sodium hydroxide. The formed precipitate was filtered and then washed with tetrahydrofuran. The filtrate was concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 1.68 g (cyclohexyl-1H-pyrazole-4-yl)methanol.

1H-NMR (CDCl3, TMS, δ(ppm)): 1,19-of 1.30 (1H, m), 1,36 is 1.75 (5H, m), 1,87 is 1.91 (2H, m), 2,13-of 2.16 (2H, m), 4.04 the-4,15 (1H, m), 4,58 (2H, c), 7,44 (1H, c), 7,49 (1H, c)

Reference example get 25-3

The hydrochloride of 4-(chloromethyl)-1-cyclohexyl-1H-pyrazole

1.68 g (1-cyclohexyl-1H-pyrazole-4-yl)methanol was dissolved in 20 ml of dichloromethane and then added 2.0 ml of chloride tiomila. The mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, obtaining 2.15 g of the hydrochloride of 1-cyclohexyl-4-(chloromethyl)-1H-feast of the Ola.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,24-of 1.36 (1H, m), 1,43 is 1.58 (2H, m), 1,73 of-1.83 (3H, m), 1,94-of 1.97 (2H, m), 2,33-is 2.37 (2H, m), of 4.54 (2H, c), 4,71-rate 4.79 (1H, m), 7,74 (1H, c), to $ 7.91 (1H, c)

Reference example receiving 26

[(1-Propargyl-1H-pyrazole-4-yl)methyl]malononitrile

0.73 g [(1-propargyl-1H-pyrazole-4-yl)methylidene]malononitrile was dissolved in 10 ml of tetrahydrofuran and then added with ice cooling to 0.19 g of sodium borohydride. The mixture was stirred for 4 hours under ice cooling. The reaction mixture was added to 0,5h. hydrochloric acid and then was exteremely with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, getting 0.32 g [(1-prop-2-inyl-1H-pyrazole-4-yl)methyl]malononitrile.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,54 (1H, t), 3,21 (2H, d), a-3.84 (1H, t), of 4.95 (2H, d), 7,55 (1H, c), 7,72 (1H, c)

Reference example get 27

[(1-tert-butyl-1H-pyrazole-4-yl)methyl]malononitrile

5,95 g malononitrile was dissolved in 30 ml of N,N-dimethylformamide and then added with ice cooling to 12.44 g of potassium carbonate. To this mixture was added dropwise over 1 hour a solution 6,27 g of the hydrochloride of 1-tert-butyl-4-(chloromethyl)-1H-pyrazole in 30 ml of N,N-dimethylformamide. After completion of addition, the mixture was stirred at anatoy temperature for 8 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 4.12 g [(1-tert-butyl-1H-pyrazole-4-yl)methyl]malononitrile.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,59 (9H, c)3,20 (2H, d), 3,81 (1H, t), 7,53 (1H, c), 7,58 (1H, c)

Reference example get 28-1

Ethyl 5-(1H-pyrrol-1-yl)-1-tert-butyl-1H-pyrazole-4-carboxylate

8,45 g of ethyl 5-amino-1-tert-butyl-1H-pyrazole-4-carboxylate was dissolved in 60 ml of acetic acid and then added to 7.93 g of 2,5-dimethoxytetrahydrofuran. The mixture was heated at the boil under reflux for 2 hours. The reaction mixture was concentrated under reduced pressure. After adding water, the residue was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 8.95 g of ethyl 5-(1H-pyrrol-1-yl)-1-tert-butyl-1H-pyrazole-4-carboxylate.

1H-NMR (CDCl3, TMS, δ (ppm)): a 1.11 (3H, t)of 1.46 (9H, c)4,08 (2H, HF), 6,33 (2H, t)6,70 (2H, t), to 7.93 (1H, c)

Reference example get 28-2

[5-(1H-pyrrol-1-yl)-1-tert-butyl-1H-feast of the evil-4-yl]methanol

1.30 grams of sociallyengaged suspended in 50 ml of tetrahydrofuran was added thereto in nitrogen atmosphere is added dropwise within 15 minutes with ice cooling a solution of 8.95 g of ethyl 5-(1H-pyrrol-1-yl)-1-tert-butyl-1H-pyrazole-4-carboxylate in 20 ml of tetrahydrofuran. The mixture was stirred for 8 hours under ice cooling. After adding water, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 7,06 g of [5-(1H-pyrrol-1-yl)-1-tert-butyl-1H-pyrazole-4-yl]methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.42 (9H, c), 4,24 (2H, c), 6,32 (2H, t), of 6.73 (2H, t), 7,56 (1H, c)

Reference example get 28-3

4-(Chloromethyl)-5-(1H-pyrrol-1-yl)-1-tert-butyl-1H-pyrazole

2.20 g of [5-(1H-pyrrol-1-yl)-1-tert-butyl-1H-pyrazole-4-yl]methanol was dissolved in 20 ml dichloromethane and added to 0.73 ml chloride tiomila. The mixture was stirred at room temperature for 1.5 hours and then concentrated under reduced pressure. After adding saturated aqueous sodium hydrogen carbonate solution, the residue was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under ponie nom pressure. The residue was chromatographically on a column of silica gel, receiving of 2.35 g of 4-(chloromethyl)-5-(1H-pyrrol-1-yl)-1-tert-butyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.42 (9H, c), 4,18 (2H, c), 6,34 (2H, t), of 6.73 (2H, t), to 7.59 (1H, c)

Reference example get 29-1

(5-Trifluoromethyl-isoxazol-3-yl)methanol

of 2.72 g of 4,4,5,5,5-pendaftar-2-iodine-2-penten-1-ol was dissolved in 7 ml of ethanol and then added 3 ml of water, 0,69 g of hydroxylamine hydrochloride and 1.38 g of potassium carbonate. The mixture was stirred and heated at the boil under reflux for 10 hours. The reaction mixture was concentrated under reduced pressure. After adding water, the residue was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0,57 g (5-trifluoromethyl-isoxazol-3-yl)methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 4,84 (2H, c), 6,79 (1H, c)

Reference example 29-2

3-(methyl bromide)-5-cryptometrics

2,47 g (5-trifluoromethyl-isoxazol-3-yl)methanol was dissolved in 80 ml of diethyl ether, and then added 6,56 g of triphenylphosphine and 8.9 g chetyrehpostovye carbon. The mixture was stirred at room temperature for 1 hour. The reaction to shift the have chromatographically on a column of silica gel, getting to 1.14 g of 3-(methyl bromide)-5-cryptomaterial.

1H-NMR (CDCl3, TMS, δ (ppm)): to 4.46 (2H, c), 6,87 (1H, c)

Reference example obtaining 30-1

1-(5-Trifluoromethyl-isoxazol-3-yl)ethanol

7,49 g of 5,5,6,6,6-pendaftar-3-iodine-3-HEXEN-2-ol was dissolved in 70 ml of ethanol and then added 30 ml of water, 3,34 g of hydroxylamine hydrochloride and 17,94 g of potassium carbonate. The mixture was stirred and heated at the boil under reflux for 48 hours. The reaction mixture was concentrated under reduced pressure. After adding water, the residue was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 1.53 g of 1-(5-trifluoromethyl-isoxazol-3-yl)ethanol.

1H-NMR(CDCl3, TMS, δ(ppm)): to 1.59 (3H, d), 5,07 (1H, HF), 6,77 (1H, c)

Reference example get 30-2

3-(1-Bromacil)-5-cryptometrics

1-(5-Trifluoromethyl-isoxazol-3-yl)ethanol was dissolved in 35 ml of diethyl ether and then added with 2.93 g of triphenylphosphine and 3,71 g chetyrehpostovye carbon. The mixture was stirred at room temperature for 1 hour. The reaction mixture was chromatographically on a column of silica gel, getting to 1.14 g of 3-(1-bromacil)-5-is reformationists.

1H-NMR (CDCl3, TMS, δ (ppm)): to 2.06(3H, d), of 5.17(1H, HF), 6,83(1H, c)

Reference example get 31-1

9,01 g 6,6,7,7,7-pendaftar-4-iodine-4-hepten-3-ol was dissolved in 70 ml of ethanol and then added 30 ml of water, 3,81 g of hydroxylamine hydrochloride and 7.51 g of potassium carbonate. The mixture was stirred and heated at boiling under reflux for 24 hours. The reaction mixture was concentrated under reduced pressure. After adding water, the residue was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 1.63 g of 1-(5-trifluoromethyl-isoxazol-3-yl)propanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 0,99 (3H, t), of 1.84 (2H, m), a 4.83 (1H, m), of 6.75 (1H, c)

Reference example get 31-2

3-(1-Bromopropyl)-5-cryptometrics

1.63 g of 1-(5-trifluoromethyl-isoxazol-3-yl)propanol was dissolved in 45 ml of diethyl ether was then added 4,20 g of triphenylphosphine and 5.31g tetrabromide carbon. The mixture was stirred at room temperature for 1 hour. The reaction mixture was chromatographically on a column of silica gel, receiving of 1.00 g of 3-(1-bromopropyl)-5-cryptomaterial.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,2 (3H, t), 2,18-to 2.29 (2H, m), 4,94 (1H, t), to 6.80 (1H, c)

Reference example get 32-1

8,9 g 4,4,5,5,6,6,6-heptathlon-2-iodine-2-HEXEN-1-ol was dissolved in 90 ml of ethanol and then added 40 ml of water, to 4.17 g of hydroxylamine hydrochloride and 20,70 g of potassium carbonate. The mixture was stirred and heated at boiling under reflux for 20 hours. The reaction mixture was concentrated under reduced pressure. After adding water, the residue was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 2,78 g (5-pentafluoroethyl-isoxazol-3-yl)methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 4,88 (2H, c), 6,85 (1H, c)

Reference example get 32-2

3-(methyl bromide)-5-pentafluorothiophenol

2,78 g (5-pentafluoroethyl-isoxazol-3-yl)methanol was dissolved in 10 ml of diethyl ether and then added a 5.25 g of triphenylphosphine and 6,63 g chetyrehpostovye carbon. The mixture was stirred at room temperature for 1 hour. The reaction mixture was chromatographically on a column of silica gel, getting to 1.83 g of 3-(methyl bromide)-5-pentafluorothiophenol.

1H-NMR (CDCl3, TMS, δ (ppm)): to 4.46 (2H, c), 6,87 (1H, c)

Reference example receive 33-1

4.94 g 4,4,5,5,6,6,7,7,7-nomatter-2-iodine-2-hepten-1-ol was dissolved in 150 ml of ethanol and then added 70 ml of water, of 5.17 g of hydroxylamine hydrochloride and 25,67 g of potassium carbonate. The mixture was stirred and heated at boiling under reflux for 24 hours. The reaction mixture was concentrated under reduced pressure. After adding water, the residue was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 3.53 g (5-heptafluoropropyl-isoxazol-3-yl)methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): a 4.86 (2H, c), 6,85 (1H, c)

Reference example get 33-2

3-(Chloromethyl)-5-heptafluoropropoxy

2,78 g (5-heptafluoropropyl-isoxazol-3-yl)methanol was dissolved in 10 ml of diethyl ether and then added a 5.25 g of triphenylphosphine and 6,63 g chetyrehpostovye carbon. The mixture was stirred at room temperature for 1 hour. The reaction mixture was chromatographically on a column of silica gel, getting to 1.83 g of 3-(chloromethyl)-5-(heptafluoropropyl)isoxazol.

1H-NMR (CDCl3, TMS, δ(ppm)): of 4.66 (2H, c), 6,89 (1H, c)

Reference example get 34-1

(5-Isopropyl-isoxazol-3-yl)methanol

20,76 g of ethyl 5-isopropyl-isoxazol-3-carboxylate was dissolved in 200 ml of ethanol, and C is the added 4,20 g of sodium borohydride. The mixture was stirred at room temperature for 10 hours. After adding 50 ml of water the reaction mixture was concentrated to a volume of 50 ml under reduced pressure. The concentrated solution was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 15,13 g (5-isopropyl-isoxazol-3-yl)methanol.

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.28 (6H, d), totaling 3.04 (1H, m), 4.72 in (2H, c), 6,01 (1H, c)

Reference example get 34-2

(5-Isopropyl-isoxazol-3-yl)methyl 4-toluensulfonate

4,24 g (5-isopropyl-isoxazol-3-yl)methanol was dissolved in 10 ml of pyridine and then added with ice cooling to 6.67 g of 4-toluensulfonate. The mixture was stirred for 5 hours under ice cooling. After adding water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 1,82 g (5-isopropyl-isoxazol-3-yl)methyl 4-toluensulfonate.

1H-NMR (CDCl3, TMS, δ(ppm)): 1,22 (3H, d), to 1.60 (3H, d), to 2.35 (3H, c), 2,93-a 3.01 (1H, m), 5,63 (2H, c), is 6.54 (1H, c), 7,30 (2H, d), 7,74 (2H, d)

Reference example polucheniya-1

5-Isopropyl-isoxazol-3-carbaldehyde

to 7.59 g (5-isopropyl-isoxazol-3-yl)methanol was dissolved in 100 ml of 1,4-dioxane and then added to 21.74 g of manganese dioxide. The mixture was stirred and heated at the boil under reflux for 10 hours. The reaction mixture was cooled to room temperature and then filtered through celite®. The filtrate was concentrated under reduced pressure, getting 6,72 g of 5-isopropyl-isoxazol-3-carbaldehyde.

Reference example get 35-2

1-(5-Isopropyl-isoxazol-3-yl)ethanol

5,70 g 5-isopropylthiazole-3-carbaldehyde was dissolved in 82 ml of 1,4-dioxane and then added with ice cooling 48 ml, 0.93 M solution methylacrylamide in tetrahydrofuran. The mixture was stirred for 1 hour under ice cooling. After adding water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, getting to 5.66 g of 1-(5-isopropyl-isoxazol-3-yl)ethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.29 (6H, d), of 1.53 (3H, d), to 3.02 (1H, m), equal to 4.97 (1H, m), 5,98 (1H, c)

Reference example get 35-3

3-(1-Chloroethyl)-5-isopropylthiazole

to 5.66 g of 1-(5-isopropyl-isoxazol-3-yl)ethanol was dissolved in 30 ml of pyridine and then added with ice cooling 7.20 g of 4-toluensulfonate. The mixture was stirred for 5 hours under ice cooling. After adding water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 3,63 g of 3-(1-chloroethyl)-5-isopropylthiazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,31 (6H, d), of 1.86 (3H, d), 3.04 from-3,10 (1H, m), 5,10 (1H, HF), the 6.06 (1H, c)

Reference example get 36-1

5-tert-Butyl-isoxazol-3-carbaldehyde

1.35 g (5-tert-butyl-isoxazol-3-yl)methanol was dissolved in 50 ml of 1,4-dioxane and then added to 6.42 per g of manganese dioxide. The mixture was stirred and heated at the boil under reflux for 10 hours. The reaction mixture was cooled to room temperature and then filtered through celite®. The filtrate was concentrated under reduced pressure, getting 1.29 g of 5-tert-butyl-isoxazol-3-carbaldehyde.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.39 (9H, c), 6.35mm (1H, c), 10,12 (1H, c)

Reference example get 36-2

1-(5-tert-Butyl-isoxazol-3-yl)ethanol

1.29 g of 5-tert-butyl-isok the azole-3-carbaldehyde was dissolved in 10 ml of tetrahydrofuran and then added 10 ml of 0.93 M solution Metalmania bromide in tetrahydrofuran. The mixture was stirred for 1 hour under ice cooling. After adding water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 1.18 g of 1-(5-tert-butyl-isoxazol-3-yl)ethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.34 (9H, c), and 1.54 (3H, d), equal to 4.97 (1H, HF), 5,96 (1H, c)

Reference example get 36-3

3-(1-Chloroethyl)-5-tert-butylisoxazole

1.18 g of 1-(5-tert-butyl-isoxazol-3-yl)ethanol was dissolved in 2 ml of pyridine and then added with ice cooling to 1.36 g of 4-toluensulfonate. The mixture was stirred for 5 hours under ice cooling. After adding water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, getting to 1.60 g of 3-(1-chloroethyl)-5-tert-butylisoxazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.34 (9H, c), and 1.54 (3H, d), equal to 4.97 (1H, HF), 5,96 (1H, c)

Reference example get 37-1

Ethyl 5-(hydroxymethyl)isoxazol-3-carboxylate

24,03 g 2-propen-1-ol and 16,24 g of ethyl (2E)-chlorine(hydroxym the but)acetate was dissolved in 100 ml of tetrahydrofuran and then added dropwise at 0° C within 30 minutes of 12.12 ml of triethylamine dissolved in 50 ml of tetrahydrofuran. The mixture was stirred at room temperature overnight. After adding a saturated aqueous solution of sodium chloride, the reaction mixture was separated into layers. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 14,22 g of ethyl 5-(hydroxymethyl)isoxazol-3-carboxylate.

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.40 (3H, t), 2,22 (1H, users.), was 4.42 (2H, q), a 4.83 (2H, d), of 6.68 (1H, c)

Reference example get 37-2

Ethyl 5-(tert-butyldimethylsilyloxy)isoxazol-5-carboxylate

14,22 g of ethyl 5-(hydroxymethyl)isoxazol-3-carboxylate was dissolved in 80 ml of N,N-dimethylformamide and then added 6,13 g of imidazole and 13,57 g of tert-butyldimethylsilyloxy. The mixture was stirred at room temperature for 10 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure, getting 23,82 g of ethyl 5-(tert-butyldimethylsilyloxy)isoxazol-3-carboxylate.

1H-NMR (CDClsub> 3, TMS, δ (ppm)): 0,12 (6H, c)of 0.91 (9H, c), of 1.52 (3H, t), 4,42 (2H, HF), to 4.81 (2H, c), 6,60 (1H, c)

Reference example get 37-3

[5-(tert-Butyldimethylsilyloxy)isoxazol-3-yl]methanol

23,82 g of ethyl 5-(tert-butyldimethylsilyloxy)isoxazol-3-carboxylate was dissolved in 100 ml of ethanol, and then added to 3.16 g of sodium borohydride. The mixture was stirred at room temperature for 4 hours. After adding 50 ml of water the reaction mixture was concentrated to a volume of 50 ml under reduced pressure. The concentrated solution was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 18,74 g of [5-(tert-butyldimethylsilyloxy)isoxazol-3-yl]methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 0,12 (6H, c)to 0.92 (9H, c), 4,62-and 4.68 (4H, m), 6,13 (1H, c)

Reference example get 37-4

3-(Chloromethyl)-5-(tert-butyldimethylsilyloxy)isoxazol

18,64 g of [5-(tert-butyldimethylsilyloxy)isoxazol-3-yl]methanol was dissolved in 80 ml of pyridine and then added with ice cooling 16,06 g of 4-toluensulfonate. The mixture was stirred for 10 hours under ice cooling. After adding water, the reaction mixture extragere the Ali ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 4,48 g of 5-(tert-butyldimethylsilyloxy)-3-(chloromethyl)isoxazol.

1H-NMR (CDCl3, TMS, δ (ppm)): 0,12 (6H, c)to 0.92 (9H,c), 4,58 (2H, c), of 4.77 (2H, c), 6,30 (1H, c)

Reference example get 38-1

Ethyl 5-(1-hydroxyethyl)isoxazol-3-carboxylate

14,02 g 1-buten-2-ol and 7,58 g of ethyl (2E)-chlorine(hydroxyimino)acetate was dissolved in 50 ml of tetrahydrofuran and then added dropwise at 0°C during 30 minutes a solution of the 6.06 g of triethylamine in 25 ml of tetrahydrofuran. The mixture was stirred at room temperature overnight. After adding a saturated aqueous solution of sodium chloride, the reaction mixture was separated into layers. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was purified column chromatography on silica gel, receiving 5,67 g of ethyl 5-(1-hydroxyethyl)isoxazol-3-carboxylate.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.33 (3H, t), of 1.57 (3H, d), 4,42 (2H, HF), 5,04 (1H, HF), 6,62 (1H, c)

Reference example get 38-2

Ethyl 5-[1-(tert-butyldimethylsilyloxy)ethyl]isoxazol-3-carbox ilat

of 5.55 g of ethyl 5-(1-hydroxyethyl)isoxazol-3-carboxylate was dissolved in 30 ml of N,N-dimethylformamide and then added 2.38 g of imidazole and 5,28 g of tert-butyldimethylsilyloxy. The mixture was stirred at room temperature for 10 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure, obtaining of 8.95 g of ethyl 5-[1-(tert-butyldimethylsilyloxy)ethyl]isoxazol-3-carboxylate.

1H-NMR (CDCl3, TMS, δ(ppm)): 0,08 (3H, c), 0,12 (3H, c)to 0.92 (9H, c)of 1.41 (3H, t), and 1.54 (3H, d), 4,42 (2H, HF), 4,99 (1H, HF), to 6.43 (1H, c)

Reference example get 38-3

{5-[1-(tert-butyldimethylsilyloxy)ethyl]isoxazol-3-yl}methanol

of 8.95 g of ethyl 5-[1-(tert-butyldimethylsilyloxy)ethyl]isoxazol-3-carboxylate was dissolved in 60 ml of ethanol and then added 2.30 g of sodium borohydride. The mixture was stirred at room temperature for 4 hours. After adding 30 ml of water the reaction mixture was concentrated to a volume of 30 ml under reduced pressure. The concentrated solution was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The remainder of the chromium which was tographically on a column of silica gel, getting to 7.35 g of {5-[1-(tert-butyldimethylsilyloxy)ethyl]isoxazol-3-yl}methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 0,08 (3H, c), 0,12 (3H, c), of 0.91 (9H, c)to 1.48 (3H, d), 4,74 (2H, c), of 4.95 (1H, HF), 6,18 (1H, c)

Reference example get 38-4

{5-[1-(tert-butyldimethylsilyloxy)ethyl]isoxazol-3-yl}methyl 4-methylbenzenesulfonate

7,35 g {5-[1-(tert-butyldimethylsilyloxy)ethyl]isoxazol-3-yl}methanol was dissolved in 50 ml of methyl tert-butyl ether and then added with ice cooling to 3.36 g of 1,4-diazabicyclo[2,2,2]octane and 5,72 g of 4-toluensulfonate. The mixture was stirred for 10 hours under ice cooling. After adding water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 3.60 g of {5-[1-(tert-butyldimethylsilyloxy)ethyl]isoxazol-3-yl}methyl 4-methylbenzenesulfonate.

1H-NMR (CDCl3, TMS, δ (ppm)): 0,05 (3H, c), 0,10 (3H, c), of 0.90 (9H, c)a 1.45 (3H, d), a 2.45 (3H, c), 4,91 (1H, HF), 5,09 (2H, c), 6,14 (1H, c), 7,34 (2H, d), 7,80 (2H, d)

Reference example get 39-1

Ethyl 5-acetylisoniazid-3-carboxylate

4,06 g of ethyl 5-(1-hydroxyethyl)isoxazol-3-carboxylate was dissolved in 100 ml of 1,4-dioxane and then added 15,20 is manganese dioxide. The mixture was stirred and heated at the boil under reflux for 5 hours. The reaction mixture was cooled to room temperature and then filtered through celite®. The filtrate was concentrated under reduced pressure, getting 3.57 g of ethyl 5-acetylisoniazid-3-carboxylate.

1H-NMR (CDCl3, TMS, δ(ppm)): of 1.40 (3H, t)to 2.67 (3H, c), of 4.45 (2H, q), 7,27 (1H, c)

Reference example get 39-2

Ethyl 5-(1,1-dottorati)isoxazol-3-carboxylate

2,61 g of ethyl 5-acetylisoniazid-3-carboxylate was dissolved in 30 ml dichloromethane was added under ice cooling 4,84 g TRIFLUORIDE (dimethylamino)sulfur. The mixture was stirred at room temperature for 4 hours. After adding a saturated aqueous solution of sodium bicarbonate, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 2,90 g of ethyl 5-(1,1-dottorati)isoxazol-3-carboxylate.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.41 (3H, t), 2,01-to 2.06 (3H, m), of 4.44 (2H, q), 6,91 (1H, c)

Reference example get 39-3

[5-(1,1-Dottorati)-3-yl]methanol

2,90 g of ethyl 5-(1,1-dottorati)isoxazol-3-carboxylate of rest rely in 30 ml of ethanol, and then added 1,02 g of sodium borohydride. The mixture was stirred at room temperature for 4 hours. After adding 30 ml of water the reaction mixture was concentrated to a volume of 30 ml under reduced pressure. The concentrated solution was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving a 2.00 g of [5-(1,1-dottorati)-3-yl]methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,97 (3H, t), 4,79 (2H, c), 6,56 (1H, c)

Reference example get 39-4

3-(Chloromethyl)-5-(1,1-dottorati)isoxazol

to 1.00 g of [5-(1,1-dottorati)isoxazol-3-yl]methanol was dissolved in 10 ml of dichloromethane and then added 0.8 ml of chloride tiomila. The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, obtaining a 1.11 g of 3-(chloromethyl)-5-(1,1-dottorati)isoxazol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,99 (3H, t), br4.61 (2H, c), is 6.61 (1H, c)

Reference example obtaining 40-1

Ethyl 5-(1-hydroxy-1-methylethyl)isoxazol-3-carboxylate

57,35 g 2-methyl-1-butyn-2-ol and 25,83 g of ethyl (2E)-chlorine(hydroxyimino)acetate was dissolved in 120 ml of tetrahydrofuran and then added dropwise at 0°C for 1 character to 17.25 g of triethylamine in 50 ml of tetrahydrofuran. The mixture was stirred at room temperature overnight. After adding a saturated aqueous solution of sodium chloride, the reaction mixture was separated into layers. The aqueous layer was extracted with ethyl acetate and the organic layers were combined, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 17,62 g of ethyl 5-(1-hydroxy-1-methylethyl)isoxazol-3-carboxylate.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.39 (3H, t), of 1.66 (6H, c)to 4.41 (2H, q), to 6.58 (1H, c)

Reference example get 40-2

[5-(1-Hydroxy-1-methylethyl)isoxazol-3-yl]methanol

9,96 g of ethyl 5-(1-hydroxy-1-methylethyl)isoxazol-5-carboxylate was dissolved in 200 ml of ethanol and then added of 3.78 g of sodium borohydride. The mixture was stirred at room temperature for 10 hours. After adding 50 ml of water the reaction mixture was concentrated to a volume of 50 ml under reduced pressure. The concentrated solution was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 6.17 g of [5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,63 (6H, c)to 2.15 (1H, users), 4,74 (2H,d), to 6.22 (1H, c)

Reference example get 40-3

5-(1-Hydroxy-1-methylethyl)isoxazol-3-carbaldehyde

5,38 g of [5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]methanol was dissolved in 100 ml of 1,4-dioxane and then added 29,74 g of manganese dioxide. The mixture was stirred and heated at the boil under reflux for 10 hours. The reaction mixture was cooled to room temperature and then filtered through celite®. The filtrate was concentrated under reduced pressure, getting 4,63 g of 5-(1-hydroxy-1-methylethyl)-isoxazol-3-carbaldehyde.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,67 (6H, c), 6,56 (1H, c), 10,14 (1H, c)

Reference example get 40-4

{[5-(1-Hydroxy-1-methylethyl)isoxazol-3-yl]methylidene}malononitrile

4,63 g of 5-(1-hydroxy-1-methylethyl)isoxazol-3-carbaldehyde was dissolved in 50 ml of ethanol and then added 1.98 g of malononitrile. The mixture was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure and the residue was chromatographically on a column of silica gel, receiving 5.35 g {[5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]methylidene}malononitrile.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,68 (6H, c), 7,01 (1H, c), 7,92 (1H, c)

Reference example get 40-5

{[5-(1-Hydroxy-1-methylethyl)isoxazol-3-yl]methyl}malononitrile

to 9.91 g {[5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]methylidene}malononitrile was dissolved in 100 ml of tetrahydrofuran and then added with ice cooling of 3.78 g of sodium borohydride. The mixture was stirred for 8 hours under ice cooling. The reaction mixture was added to 0,5h. hydrochloric acid for 30 minutes and then was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 5,38 g {[5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]methyl}malononitrile.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.64 (6H, c), 3,40 (2H, d), 4,25 (1H, t), and 6.25 (1H, c)

Reference example obtain 41

{1-[5-(1-Hydroxy-1-methylethyl)isoxazol-3-yl]ethyl}malononitrile

1,02 g {[5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]methylidene}malononitrile was dissolved in 50 ml of 1,4-dioxane. To the solution was added 0.05 g of copper iodide(I) and then added with ice cooling 9 ml of 1.4 M solution Metalmania bromide in tetrahydrofuran. The mixture was stirred for 1 hour under ice cooling. The reaction mixture was added to 0.1 M hydrochloric acid and then was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The remainder of chromatography the Wali on a column of silica gel, receiving of 0.53 g of {1-[5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]methyl}malononitrile.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,61 by 1.68 (9H, m), 3,57-the 3.65 (1H, m), 4,27 (1H, d), 6,23 (1H, c)

Reference example obtain 42

{1-[5-(1-Hydroxy-1-methylethyl)isoxazol-3-yl]propyl}malononitrile

1,02 g {[5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]methylidene}malononitrile was dissolved in 50 ml of 1,4-dioxane. To the solution was added 0.05 g of copper iodide(I) and then added with ice cooling, 5 ml of 3 M solution of etimani bromide in tetrahydrofuran. The mixture was stirred for 1 hour under ice cooling. The reaction mixture was added to 0.1 M hydrochloric acid and then was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.40 g of {1-[5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]propyl}malononitrile.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,24 (3H, t), of 1.70 (6H, c), 1,96 and 2.13 (2H, m), 3,41 is-3.45 (1H, m), 4,11 (1H, d), and 6.25 (1H, c)

Reference example receiving 43

{1-[5-(1-Hydroxy-1-methylethyl)isoxazol-3-yl]-2-methylpropyl}malononitrile

1,02 g {[5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]methylidene}malononitrile was dissolved in 50 ml of 1,4-dioxane. To the solution was added 0.05 g of copper iodide(I) and then time to relax is when ice cooling, 15 ml of 1 M solution Isopropylamine bromide in tetrahydrofuran. The mixture was stirred for 1 hour under ice cooling. The reaction mixture was added to 0.1 M hydrochloric acid and then was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.40 g of {1-[5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]-2-methylpropyl}malononitrile.

1H-NMR (CDCl3, TMS, δ(ppm)): of 0.91 (3H, d), of 1.12 (3H, d), of 1.65 (6H, c), 2,31-to 2.40 (1H, m), with 3.27 (1H, t), 4,25 (1H, d), 6,23 (1H, c)

Reference example receiving 44

{1-[5-(1-Hydroxy-1-methylethyl)isoxazol-3-yl]allyl}malononitrile

of 2.26 g of {[5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]methylidene}malononitrile was dissolved in 50 ml of 1,4-dioxane. To the solution was added 0.05 g of copper iodide(I) and then added with ice cooling to 18.6 ml of 1.4 M solution Allemagne chloride in tetrahydrofuran. The mixture was stirred for 1 hour under ice cooling. The reaction mixture was added to 0.1 M hydrochloric acid and then was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.56 g of {1-[5-(1-hydroxy-1-methylethyl)isoxazol-3-yl]allyl}malononitrile.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.64 (6H, c), 05-4,08 (1H, m), and 4.40 (1H, d), 5,55-5,62 (2H, m), 5,97-the 6.06 (1H, m), 6,18 (1H, c)

Reference example get 45-1

Ethyl 5-[1-methyl-1-(2-propenyloxy)ethyl]isoxazol-3-carboxylate

a 2.00 g of ethyl 5-(1-hydroxy-1-methylethyl)isoxazol-3-carboxylate was dissolved in 20 ml of tetrahydrofuran and then added with ice cooling of 0.44 g of sodium hydride and of 1.32 g of 3-bromo-1-propene. The mixture was stirred at room temperature for 5 hours. After adding water, the reaction mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel and then recrystallized from a mixture of hexane-ethyl acetate, receiving 0.25 g of ethyl 5-[1-methyl-1-(2-propenyloxy)ethyl]isoxazol-3-carboxylate.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.41 (3H, t), of 1.66 (6H, c)2,39 (1H, t), of 4.00 (2H, d), 4,42 (2H, HF), only 6.64 (1H, c)

Reference example get 45-2

{5-[1-Methyl-1-(2-propenyloxy)ethyl]isoxazol-3-yl}methanol

0.25 g of ethyl 5-[1-methyl-1-(2-propenyloxy)ethyl]isoxazol-3-carboxylate was dissolved in 2 ml of ethanol and then added 0.1 g of sodium borohydride. The mixture was stirred at room temperature for 5 hours. After adding 20 ml of water the reaction mixture was exteremely utilized the volume. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 0.20 g {5-[1-methyl-1-(2-propenyloxy)ethyl]isoxazol-3-yl}methanol.

1H-NMR(CDCl3, TMS, δ(ppm)): 1,63(6H, c)2,39(1H, t)to 4.01(2H, d), was 4.76(2H, c), of 6.29(1H, c)

Reference example get 45-3

3-(Chloromethyl)-5-[1-methyl-1-(2-propenyloxy)ethyl]isoxazol

0.20 g {5-[1-methyl-1-(2-propenyloxy)ethyl]isoxazol-3-yl}methanol was dissolved in 5 ml of dichloromethane and then added 0.5 ml of chloride tiomila. The mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, getting 0.21 g of 3-(chloromethyl)-5-[1-methyl-1-(2-propenyloxy)ethyl]isoxazol.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.64 (6H, c)2,39 (1H, t), was 4.02 (2H, d), 4,58 (2H, c), 6,33 (1H, c)

Reference example get 46-1

Methyl 3-methoxyethoxy-5-carboxylate

2.86 g of methyl 3-hydroxyethoxy-5-carboxylate was dissolved in 10 ml of N,N-dimethylformamide and then added with ice cooling 4,25 g iodotope bromide and 4.15 g of potassium carbonate. The mixture was stirred at room temperature overnight. The reaction mixture was added to 0.1 M hydrochloric acid and then was extracted with ethyl acetate. The organic layer is left the house taking over anhydrous magnesium sulfate, was filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 2.23 g of methyl 3-methoxyethoxy-5-carboxylate.

1H-NMR (CDCl3, TMS, δ (ppm)): 3,93 (3H, c), of 4.05 (3H, c), is 6.54 (1H, c)

Reference example get 46-2

(3-Methoxyethoxy-5-yl)methanol

of 2.23 g of methyl 3-methoxyethoxy-5-carboxylate was dissolved in 30 ml of ethanol and then added with ice cooling to 0.60 g of sodium borohydride. The mixture was stirred for 8 hours under ice cooling. After adding water under ice cooling, the reaction mixture was concentrated under reduced pressure and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 1.55 g (3-methoxyethoxy-5-yl)methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 3,96 (3H, c), of 4.66 (2H, c), 5,88 (1H, c)

Reference example get 46-3

5-(Chloromethyl)-3-methoxyethoxy

1.55 g (3-methoxyethoxy-5-yl)methanol was dissolved in 30 ml of dichloromethane, and then added 2 ml of chloride tiomila. The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, is the learn of 1.30 g of 5-(chloromethyl)-3-methoxyethanol.

1H-NMR (CDCl3, TMS, δ(ppm)): 3,98 (3H, c), of 4.49 (2H, c), 5,97 (1H, c)

Reference example get 47-1

(2 Ethylthio-1-Mei-5-yl)methanol

4,33 g (1-methyl-2-mercaptoimidazole-5-yl)methanol was added to 90 ml of tetrahydrofuran. To this solution was then added with ice cooling 3,70 g of tert-butoxide potassium and 5,15 g iodine ethyl. The mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving 4,82 g (2 ethylthio-1-Mei-5-yl)methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.32 (3H, t), 3,06 (2H, d), 3,24 (2H, HF), to 3.64 (3H, c), of 7.00 (1H, c)

Reference example get 47-2

2 Ethylthio-1-Mei-5-carbaldehyde

5.50 g (2 ethylthio-1-Mei-5-yl)methanol was dissolved in 100 ml of 1,4-dioxane and then added 24,34 g of manganese dioxide. The mixture was stirred and heated at the boil under reflux for 7 hours. The reaction mixture was cooled to room temperature and then filtered through celite®. The filtrate was concentrated under reduced pressure, getting 5,13 g 2 ethylthio-1-Mei-5-carbaldehyde.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.41 (3H, t), 3,26 (2H, HF), 3,83 (3H, c), 7,73 (1H, c), 9,58 (1H, c)

silecky example of getting 47-3

[(2-Ethylthio-1-Mei-5-yl)methylidene]malononitrile

5,13 g 2 ethylthio-1-Mei-5-carbaldehyde was dissolved in 30 ml of ethanol and then added to 2.00 g of malononitrile. The mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, receiving of 2.51 g of [(2-ethylthio-1-Mei-3-yl)methylidene]malononitrile.

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.38 (3H, t), 3,30 (2H, q), of 3.56 (3H, c), 7,39 (1H, c), 8,46 (1H, c)

Reference example get 47-4

{(2-Ethylthio-1-Mei-5-yl)methyl}malononitrile

of 0.44 g of [(2-ethylthio-1-Mei-5-yl)methylidene]malononitrile was dissolved in 10 ml of tetrahydrofuran and then added with ice cooling 0.10 g sodium borohydride. The mixture was stirred for 4 hours under ice cooling. The reaction mixture was added to 0.5 g of hydrochloric acid while cooling with ice and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was chromatographically on a column of silica gel, getting 0.32 g [(2-ethylthio-1-Mei-5-yl)methyl]malononitrile.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,31 (3H, t), 3,06 (2H, HF), to 3.34 (2H, d)and 3.59 (3H, c), 3,93 (1H, t) 7,14 (1H, c)

Next will be described examples of the drugs. The term "part" refers to parts by weight. Additionally, this connection will be indicated by use of the above compounds.

Sample preparation 1

9 parts of any one of the present compounds (1)to(70) is dissolved in a 37.5 parts of xylene and 37.5 parts of N,N-dimethylformamide. To this mixture is added 10 parts polyoxyethyleneglycol simple ether and 6 parts of dodecylbenzenesulfonate calcium and mixed by thorough mixing, getting the emulsion.

Example product 2

5 Parts of SORPOL 5060 (registered trade name of TOHO Chemical Industry Co., LTD.) added to 40 parts of any one of the present compounds (1)to(70) and thoroughly mixed. Then added to this mixture of 32 parts of CARPLEX #80 (registered trade name of Shionogi & Co., Ltd., fine synthetic anhydrous silica) and 23 parts of diatomaceous earth 300 mesh and mixed with a mixer for juice, getting wettable drug.

The example of the drug 3

3 of any one of the present compounds (1)to(70), 5 parts of fine synthetic hydrated silicon oxide, 5 parts of dodecylbenzenesulfonate sodium, 30 parts of bentonite and 57 parts of clay were mixed by thorough mixing. To this mixture was added a suitable amount of water. CME is additionally stirred, was granulated using a granulator and then dried in the air, receiving granules.

Sample preparation 4

4,5 of any one of the present compounds (1)to(70), 1 part of fine powder of synthetic hydrated silica, 1 part Dorires B (manufactured by Sankyo) as flocculant, and 7 parts of clay were thoroughly mixed using a mortar, and then mixed using a mixer for juice. To the mixture was added 86,5 parts of cut clay and mixed by thorough mixing, getting the powder.

Sample preparation 5

10 parts of any one of the present compounds (1)to(70), 35 parts of white carbon, containing 50 parts of ammonium salt of polyoxyethylenesorbitan, and 55 parts of water are mixed and then finely pulverized using wet granulation, receiving the drug.

Sample preparation 6

0.5 Parts of any one of the present compounds (1)to(70) is dissolved in 10 parts of dichloromethane. This solution is mixed with and 89.5 parts of Isopar M (isoparaffin registered trade name of Exxon Chemical), and receiving the oil.

Example of preparation 7

0.1 Part of any one of the present compounds (1)to(70) and 49.9 parts of the NEO-TIOZOL (Chuo Kasei Co., Ltd.) was placed in an aerosol container. In the container was inserted aerosol valve and loaded into the container 25 parts of dimethyl simple ether and 25 parts of LPG. Con is einer shaken in a container insert actuator, getting oil spray.

Example of preparation 8

In the aerosol container was loaded a mixture of 0.6 part of any one of the present compounds (1)to(70), 0.01 part of BHT, 5 parts of xylene, 3.39 parts of deodorized kerosene and 1 part emulsifying agent [Atmos 300 (registered trade name of the company Atmos Chemical Ltd.)] and 50 parts of distilled water. To the container was attached to the valve and then through the valve at high pressure were loaded into the container 40 parts of a propellant (LPG), receiving water spray.

Then, using experimental examples will be shown that this compound is effective as an active ingredient of the pesticide composition. This connection will be indicated by use of the above compounds.

Experimental example 1

To obtain experimental pesticide solutions preparations of the present compounds(1), (2), (3), (4), (5), (6), (8), (9), (11), (12), (13), (15), (16), (17), (18), (19), (21), (22), (23), (24), (25), (26), (27), (29), (31), (32), (34), (35), (36), (37), (38), (39), (40), (41), (42), (43), (45), (47), (50), (52), (53), (54), (62), (64), (65), (67) and (68), obtained in accordance with an example of obtaining the drug 5, was diluted so that the concentration of the active ingredient was 500 parts per million.

In a plastic Cup was placed 50 g molded Bonsoru 2 (manufacturer Sumitomo Chemical Co., Ltd.) and sown from 10 to 15 semanas. The rice plants were grown to the stage of the formation of the second sheet and then cut to a uniform height of 5 cm Obtained as described above, experimental pesticide solution was sprayed onto the rice plants in the amount of 20 ml/Cup. After drying of the sprayed onto the rice plants pesticide solution, the rice plants were placed in a plastic Cup to prevent the escape of the tested pests. 30 larvae first stagesNilaparvata lugensreleasedin a plastic Cup and closed Cup with a lid and kept in a greenhouse (25°C). On the sixth day after the release of larvaeNilaparvata lugensinvestigated the number of parasitesNilaparvata lugenson the rice plants.

As a result, when processing these compounds(1), (2), (3), (4), (5), (6), (8), (9), (11), (12), (13), (15), (16), (17), (18), (19), (21), (22), (23), (24), (25), (26), (27), (29), (31), (32), (34), (35), (36), (37), (38), (39), (40), (41), (42), (43), (45), (47), (50), (52), (53), (54), (62), (64), (65), (67) and (68), the number of parasitic pests was 3 or less.

Experimental example 2

To obtain experimental pesticide solutions preparations of the present compounds(1), (2), (4), (5), (6), (8), (11), (15), (17), (19), (24), (25), (27), (35), (36), (37), (38), (39), (40), (41), (42), (45), (47), (48), (49), (50), (52), (53), (54), (62), (65), (66), (67) and (70), obtained in accordance with the example of obtaining the drug 5 was diluted with water so that the concentration of the active ingredient was 500 cha the TEI in a million.

In a polyethylene Cup was planted cucumber and grew to the stage of development of the first sheet. About 20Aphis gossypiiput to parasitism on the cucumber. Through the day the pesticide solution was sprayed on cucumber in the amount of 20 ml/Cup. Six days to determine the number ofAphis gossypii.

As a result, when processing these compounds(1), (2), (4), (5), (6), (8), (11), (15), (17), (19), (24), (25), (27), (35), (36), (37), (38), (39), (40), (41), (42), (45), (47), (48), (49), (50), (52), (53), (54), (62), (65), (66), (67) and (70), the number of parasitic pests six days after treatment was 3 or less.

Experimental example 3

To obtain experimental pesticide solutions preparations of the present compounds(1), (2), (3), (4), (5), (6), (8), (9), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (21), (22), (23), (24), (25),(26), (27),(31), (34), (35), (36), (37), (38), (39), (40), (42), (47), (50), (52), (54), (66), (67) and (68), obtained in accordance with the example of preparation 5 was diluted with water so that the concentration of the active ingredient was 500 parts per million.

Filter paper having a diameter of 5.5 cm was placed at the bottom of a polyethylene Cup having a diameter of 5.5 cm, and was added dropwise to a filter paper 0.7 ml experimental pesticide solution. As bait evenly placed on filter paper 30 mg of sucrose. In a polyethylene Cup was released 10 adult femalesMusca domesticaand a Cup of closing the Lee cover. After 24 hours to determine the number of survivorsMusca domesticaand calculated the degree of mortality of the pests.

As a result, when processing these compounds(1), (2), (3), (4), (5), (6), (8), (9), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (21), (22), (23), (24), (25), (26), (27), (31), (34), (35), (36), (37), (38), (39), (40), (42), (47), (50), (52), (54), (66), (67) and (68), the degree of mortality of the pests was 90% or more.

Experimental example 4

To obtain experimental pesticide solutions preparations of the present compounds(2), (4), (5), (6), (8), (9), (11), (12), (13), (15), (17), (18), (19), (21), (24), (25), (26), (27), (35), (36), (37), (38), (40), (41), (42), (47), (50), (52), (54), (62), (64), (65), (66) and (68), obtained in accordance with the example of preparation 5 was diluted with water so that the concentration of the active ingredient was 500 parts per million.

Filter paper having a diameter of 5.5 cm was placed at the bottom of a polyethylene Cup having a diameter of 5.5 cm, and was added dropwise to a filter paper 0.7 ml experimental pesticide solution. As bait evenly placed on filter paper 30 mg of sucrose. In a polyethylene Cup was released two adult malesBlattalla germanicaand the Cup was covered with the lid. After 6 days to determine the number of survivorsBlattalla germanicaand calculated the degree of mortality of the pests.

As a result, when processing these compounds(2), (4), (5), (6), (8), (9), (11), (12), (13), (15), (17), (18), (9), (21), (24), (25), (26), (27), (35), (36), (37), (38), (40), (41), (42), (47), (50), (52), (54), (62), (64), (65), (66) and (68), the degree of mortality of the pests was 100%.

Experimental example 5

To obtain experimental pesticide solutions preparations of the present compounds(1), (2), (4), (5), (6), (8), (9), (11), (12), (13), (14), (15), (16), (17), (18), (19), (21), (22), (23), (24), (25), (26), (27), (31), (33), (34), (35), (36), (37), (38), (39), (40), (42), (43), (47), (48), (50), (52), (53), (54), (62), (64), (65), (66), (67), (68) and (70), obtained in accordance with example of preparation 5 was diluted with water so that the concentration of the active ingredient was 500 parts per million.

0.7 ml of the experimental pesticide solution was added to 100 ml of water after ion-exchange treatment (concentration of active ingredient : 3.5 parts per million). The solution was freed of 20 larvaeCulex pipiens pallensat the last stages. A day later estimated the number of surviving larvae and calculated the degree of mortality.

As a result, when processing these compounds(1), (2), (4), (5), (6), (8), (9), (11), (12), (13), (14), (15), (16), (17), (18), (19), (21), (22), (23), (24), (25), (26), (27), (31), (33), (34), (35), (36), (37), (38), (39), (40), (42), (43), (47), (48), (50), (52), (53), (54), (62), (64), (65), (66), (67), (68) and (70) the degree of mortality of the pests was 95% or more.

Industrial applicability

Connection malononitrile represented by the formula (I), can be used as the active ingredient of the pesticide composition.

p> 1. Connection malononitrile represented by the formula (I)

where any one of X1X2X3and X4represents CR100,

where R100represents a group represented by the formula

where R1represents a C1-C5 alkyl, C2-C5 of alkenyl or hydrogen

R2represents hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl or hydrogen

or R3and R4taken together, represent a C4-C6 alcander,

each of the other three X1X2X3and X4represents nitrogen or CR5provided that from one to three X1X2X3and X4represents nitrogen,

Z represents oxygen, sulfur or NR6,

R5independently represents halogen, formyl, carboxyl, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted C1-NW-alkyl, C1-C5 alkoxy, C3-C6, alkyloxy, C1-C5, alkylthio, C1-C5 alkylsulfonyl, the group presents NR10R11, a group represented by C(OR19R20R21elevatored,

R6represents a C1-C5 alkyl, C3-C5 quinil, C3-C6 cycloalkyl, a group represented by (CH2)mQ, or hydrogen, and

when CR5and NR6are related to each other, taken together, they may represent a C4-C6 alkerdeel in which one methylene group forming alkerdeel substituted NR6,

the group presented NR10R11is 1-pyrrolidon,

R19represents a C3-C5 quinil, Tris-Salicylic, or hydrogen,

each of R20and R21represents a C1-C5 alkyl or hydrogen,

Q represents phenyl,

m is an integer from 0 to 5.

2. Connection malononitrile according to claim 1, represented by formula (I-i)

where R1, R2, R3, R4and Z are defined in claim 1, one to three of the X2X3and X4represents nitrogen, and when one or two of X2X3and X4represents nitrogen, the other two or one are CR5and R5defined in claim 1.

3. Connection malononitrile according to claim 1, represented by formula (I-ii)

where R1, R2, R3, R4and Z are defined in claim 1, one to three of the X2X3and X4 represents nitrogen, and when one or two of X2X3and X4represents nitrogen, the other two or one are CR5and R5defined in claim 1.

4. Connection malononitrile according to claim 1, represented by any of formulas (II-i)to(II-xiii)

where R1represents a C1-C5 alkyl, C2-C5 of alkenyl or hydrogen

R2represents hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl or hydrogen

or R3and R4taken together, represent a C4-C6 alcander,

R5represents halogen, formyl, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, substituted C1-C3 alkyl, C1-C5 alkoxy, C3-C6, alkyloxy, C1-C5, alkylthio, C1-C5 is alkylsulfonyl, the group represented by C(OR19R20R21or hydrogen,

R6represents a C1-C5 alkyl,

R19represents a C3-C5 quinil or hydrogen, and

each of R20and R21represents a C1-C5 alkyl or hydrogen.

5. Connection malononitrile according to claim 4, where R1represents hydrogen,

R2represents hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl or hydrogen

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, C1-C5 alkoxy, C3-C6, alkyloxy, C1-C5, alkylthio, C1-C5 alkylsulfonyl, a group represented by C(OR19R20R21or hydrogen,

R6represents a C1-C5 alkyl,

R19represents a C3-C5 quinil or hydrogen, and

each of R20and R21represents a C1-C5 alkyl or hydrogen.

6. Connection malononitrile according to claim 1, which is represented by formula (II-i)

where R1represents a C1-C5 alkyl, C2-C5 of alkenyl or hydrogen

R2represents hydrogen,

each of R3and R4is-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl or hydrogen

or R3and R4taken together, represent a C4-C6 alcander,

R5represents halogen, formyl, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 cycloalkyl, optionally substituted C1-C3 alkyl, C1-C5 alkoxy, C3-C6, alkyloxy, C1-C5, alkylthio, C1-C5 alkylsulfonyl, a group represented by C(OR19R20R21or hydrogen,

R6represents a C1-C5 alkyl,

R19represents a C3-C5 quinil or hydrogen, and

each of R20and R21represents a C1-C5 alkyl or hydrogen.

7. Connection malononitrile according to claim 1, which is represented by formula (II-ii)

where R1, R2, R3, R4and R5defined in item 6.

8. Connection malononitrile according to claim 1, which is represented by formula (II-iii)

where R1, R2, R3, R4, R5and R6defined in item 6.

9. Connection malononitrile according to claim 1, which is represented by formula (II-iv)

where R1, R2, R3, R4and R5defined in item 6.

10. Connection malononitrile according to claim 1, to the / establishment, which is represented by formula (II-v)

where R1, R2, R3, R4and R5defined in item 6.

11. Connection malononitrile according to claim 1, which is represented by formula (II-vi)

where R1, R2, R3, R4and R5defined in item 6.

12. Connection malononitrile according to claim 1, which is represented by formula (II-vii)

where R1, R2, R3, R4and R5defined in item 6.

13. Connection malononitrile according to claim 1, which is represented by formula (II-viii)

where R1, R2, R3, R4and R5defined in item 6.

14. Connection malononitrile according to claim 1, which is represented by formula (II-ix)

where R1, R2, R3, R4, R5and R6defined in item 6.

15. Connection malononitrile on any of PP-14, where R1represents hydrogen, R2represents hydrogen,

each of R3and R4represents a C1-C5 alkyl, optionally substituted by one or more halogen, C2-C5 of alkenyl or hydrogen

R5represents halogen, C1-C5 alkyl, optionally substituted by one or more halogen, C3-C6 is cloaker, C1-C5 alkoxy, C3-C6, alkyloxy, C1-C5, alkylthio, a group represented by C(OR19R20R21or hydrogen,

R6represents a C1-C5 alkyl,

R19represents a C3-C5 quinil or hydrogen, and

each of R20and R21represents a C1-C5 alkyl or hydrogen.

16. Pesticidal composition for the control of pests of agriculture, containing an effective amount of a compound of malononitrile according to claim 1 and an inert carrier.

17. A method of combating pests comprising applying an effective amount of a compound of malononitrile according to claim 1 on a specified pest or a habitat of a specified pest.

18. The use of compounds of malononitrile according to claim 1 as an active ingredient of a pesticidal composition for the control of pests of agriculture.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to the method of obtaining the compound of the formula (IV) , which includes the epoxidation of the compound of the formula (I) the agent of oxidation in the presence of optically active compound with the formation of the compound of formula (II) , adding the gent to break the reaction, in order to extinguish any surplus oxidising agent present, where the agents for breaking the reaction are tri(C1-C6)alkylphosphite; without the isolation of the compound of the formula (II), the interaction of the reaction mixture, which includes the compound of the formula (III) in the presence of the base and the cleaning of the compound of the formula (IV) by crystallisation. The invention also relates to the method of obtaining the compound of the formula (IX) , which includes the reaction of the compound of formula (IV) with a silylation agent with the formation of a compound of the formula (V) ; the reaction of the compound of formula (V) with the silylation agent of the formula R'SO2X, where R' represents the remainder of sulfonic acid (C1-C6) alkyl and the X represents the detached group, with the obtaining of the compound of formula (VII) ; the substitution of the sulphonyloxy-group with the obtaining of the compound of the formula (VIII) and reaction of the compound of the formula (VIII) with ammonia or a compound of ammonia obtaining a compound of the formula (IX). The invention also relates to the intermediate compounds (V) and (VI) The compound of the formula (IX) can be used for obtaining a biologically active material - (S, S) - reboxetin. . In the given structural formulas pit independently are equal to 0 or a whole number from 1 up to 5; each of the groups R and R1, which can be identical or different, represents C1-C6 alkoxy or C1-C6 alkyl; P represents the protective group; R' represents the remainder of sulfonic acid (C1-C6) alkyl.

EFFECT: obtaining aril ethers.

14 cl, 5 ex

FIELD: organic chemistry, chemical technology, vitamins.

SUBSTANCE: invention relates to novel intermediate compounds used for synthesis of derivatives of vitamin D and represented by the formula (I): wherein Y1 represents hydrogen atom or tert.-butyldimethylsilyl group; Y2 represents tert.-butyldimethylsilyl group; Y3 represents hydrogen atom or tetrahydro-2-pyranyl group wherein Y3O-group is in R-configuration; R1 and R2 are bound and form methylene group. Except for, invention relates to novel compounds represented by the formula (II): wherein Y2 represents tert.-butyldimethylsilyl group; Y3 represents hydrogen atom or tetrahydro-2-pyranyl group and Y3O-group is in R-configuration. These compounds are used as intermediate substances for synthesis of compounds of the formula (I).

EFFECT: valuable properties of intermediate compounds.

8 cl, 1 dwg, 8 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention describes mercaptosilanes of the general formula (I): wherein R1 represents residue of simple alkyl polyester of the formula: -O-(R5-O)m-R6. These compounds are synthesized by the catalytic interaction of a corresponding silane with an alkoxylated alcohol R1-H by splitting off group R7-OH. And this group R7-OH is removed from the reaction mixture in continuous or periodic regimen. Indicated mercaptosilanes are used as components of rubber mixtures. Rubber mixture is prepared by mixing rubber or rubber mixture, filling agent and, if necessary, additional components and at least one indicated mercaptosilane in a corresponding mixer for rubber. Claimed mercaptosilanes are used in making molded articles, pneumatic tires, race protectors, cable envelopes, hoses, driving belts, conveyer bands, covers for different rollers, tires, shoes soles, thickening rings and shock absorbers. Taking into account economy, short duration of process in mixing components and under providing conditions for possibility the following processing the claimed mercaptosilanes allow attaining high strengthening degree, minimizing hysteresis losses and enhancing stability against abrasion in simultaneous decreasing releasing alcohols to environment as compared with trimethoxy- and triethoxy-substituted mercaptosilanes.

EFFECT: improved method of synthesis, valuable properties of rubber mixtures.

16 cl, 16 tbl, 23 ex

FIELD: chemistry of polymers, chemical technology.

SUBSTANCE: invention relates to sulfoxides or sulfones grafted on polymers, polymeric compositions, a method for grafting and method for stabilization of polymers. Invention describes polymers comprising a grafted compound of the formula (I): [R1-SOm]n-R-SOp-R2 (I) wherein total symbols have values given in cl. 1 of the invention claim and represents a composition comprising thereof, a method for grafting compound of the formula (I) on polymers and a method for stabilization of polymers. Polymers comprising grafted sulfoxides or sulfones possess high stability against oxidative, thermal, dynamic destruction caused by the light effect and/or destruction caused by ozone effect.

EFFECT: improved preparing method, improved and valuable properties of polymers.

14 cl, 14 tbl, 24 ex

FIELD: organosilicon compounds in rubber industry.

SUBSTANCE: invention provides organosilicon compounds of formula I and/or II:

, where R represents methyl or ethyl group; R', identical or different, branched or linear C9-C30-alkyl or C9-C30-alkenyl, aryl, arylalkyl, branched or linear C2-C30-alkyl ether group, branched or linear C2-C30-alkyl polyether group, R'''3Si group, wherein R''' represents branched or linear alkyl or alkenyl, arylalkyl, or aryl; R' represents branched or linear, saturated or unsaturated aliphatic, aromatic, or mixed aliphatic/aromatic group with double bond; X is O(C=O)-R''' when n=1 and m=1, SH when n=1 and m=1, S when n=2 and m=1 to 10 and mixture thereof, S(C=O)-R''' when n=1 and m=1, or H when n=1 and m=1; which are prepared by reaction of silanes of general formula III:

with alcohols of general formula R'-OH, which reaction also produces R-OH. The latter is continuously separated from reaction mixture.

EFFECT: extended resource of curing agents in rubber vulcanization processes.

8 cl, 7 tbl, 25 ex

FIELD: chemical technology, catalysts.

SUBSTANCE: invention relates to catalytic systems used in polymerization of alpha-olefins, methods for preparing catalytic systems for polymerization of alpha-olefins and methods for polymerization (and copolymerization) of alpha-olefins. Invention describes the catalytic system for polymerization of olefins comprising solid titanium component of catalyst, organoaluminum compound comprising at least one bond aluminum-carbon and organosilicon compound comprising at least one (cycloalkyl)-methyl group used as an external donor of electrons. Also, invention describes the catalytic system for polymerization of olefins comprising solid titanium component of the catalyst prepared by contacting titanium compound with magnesium compound and comprising from about 0.01 to about 500 moles of titanium compound per one mole of magnesium compound, organoaluminum compound comprising at least one bond aluminum-carbon wherein the mole ratio of aluminum to titanium in the catalytic system is in the range from about 5 to about 1000, and organosilicon compound comprising at least one (cycloalkyl)-methyl group and used a external donor of electrons wherein the mole ratio of organoaluminum compound and organosilicon compound in the catalytic system is in the range from about 2 to about 90. Also, invention describes methods for preparing catalyst used in polymerization of olefins and comprising interaction of Grignard reactive comprising (cycloalkyl)-methyl group with ortho-silicate to form organosilicon compound comprising a (cycloalkyl)-methyl link, mixing organosilicon compound with organoaluminum compound comprising at least one bond aluminum-carbon and solid titanium component of the catalyst to form the catalyst, and a method for polymerization of olefins. Invention provides preparing propylene block-copolymer showing good fluidity in the melt, capacity for molding, hardness, impact viscosity and impact strength in combination with high effectiveness of the catalyst and good technological effectiveness of the preparing process.

EFFECT: improved and valuable properties of catalysts.

17 cl, 10 ex

FIELD: organosilicon compounds.

SUBSTANCE: invention describes monohydroxysilane polysulfide of the formula: wherein radicals R can be similar or different and mean hydrocarbon groups comprising from 1 to 15 atoms; radicals R' are similar or different and mean bivalent binding groups comprising from 1 to 15 carbon atoms; x = 2 or above. Also, invention relates to a method for its preparing and using this hydroxysilane as a binding agent in rubber mixtures.

EFFECT: improved preparing method.

26 cl, 2 tbl

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention describes a method for preparing organosilylalkylpolysulfanes of the general formula (I): (R1R2R3SiR4)2Sx by interaction of organosilylalkylpolysulfanes of the general formula (II): (R1R2R3SiR4)2Sy with ionic sulfide of the general formula (III): M+2S2- and with organosilylalkyl halide of the general formula (I): R1R2R3SiR4X. Method involves preliminary the combine loading long-chain organosilylalkylpolysulfane of the general formula (II) and organosilylalkyl halide of the general formula (IV) into reactor and addition ionic sulfide of the general formula (III) to this solution by some portions.

EFFECT: improved preparing method.

3 cl, 34 ex

FIELD: organic chemistry, in particular blocked mercaptosilane cross-linking agents.

SUBSTANCE: claimed blocked cross-linking agent is obtained by reaction of 3-chloropropyltriethoxysilane and sodium 2-mercaptobenzothiazolate in isopropyl alcohol solution at 80-82°C. Mixture is agitated at this temperature for 15-20 h, cooled and alcohol is distilled followed by separation of finished product from sodium chloride. Cross-linking agent of present invention is useful in rubber mixtures based on non-polar polydienes with silicic acid and mineral fillers to simplify dispersion thereof in mixtures.

EFFECT: rubbers with decreased hysteresis.

1 tbl, 4 ex

FIELD: organic chemistry, chemistry of polymers.

SUBSTANCE: invention describes new polyfunctional siloxane oligomers of asymmetric structure of the general formula (I): (C2H5O)3SiO[Si(CH3)2O]nSi(CH3)2A wherein A means hydrogen atom (H) or the following radicals: -CH2Cl; -CH=CH2; -H2OC(O)C(CH3)=CH2; -(CH2)3OC(O)C(CH3)=CH2; -(CH2)3OCH2CH(O)CH2; n = 0 or 3, and a method for their preparing. Invention provides preparing new compounds comprising asymmetric molecules that can be used as the parent compounds in preparing polyfunctional organosiloxanes of three-dimensional polycyclic structures.

EFFECT: improved preparing method.

24 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention concerns compounds of the formula I , where R0 is 1) monocyclic 6-14-member aryl, where aryl is independently mono-, di- or trisubstituted by R8, 2) heterocyclyl out of group of benzothiazolyl, indazolyl, pyridyl, where the said heterocyclyl is independently non-substituted or mono-, di- or trisubstituted by R8, and other radicals referred to in point 1 of the claim; R8 is halogen; on condition that R8 is at least one halogen atom if R0 is monocyclic 6-14-member aryl; substructure in the formula I is 4-8-member saturated, partly non-saturated or aromatic cyclic group including 0, 1 heteroatom selected out of nitrogen or sulfur, and is non-substituted or substituted 1, 2, 3 times by R3; Q is -(C0-C2)alkylene-C(O)NR10-, methylene; R1 is hydrogen atom, -(C1-C4)alkyl, where alkyl is non-substituted or substituted one to three times by R13; R2 is a direct link; R1-N-R2-V can form 4-8-member cyclic group selected out of piperazine or piperidine group; R14 is halogen, =O, -(C1-C8)alkyl, -CN; V is 1) 6-14-member aryl, where aryl is independently non-substituted or mono-, di- or trisubstituted by R14, and other radicals referred to in point 1 of the claim; G is direct link, -(CH2)m-NR10, where m is 0 and R10 is hydrogen, -(CH2)m-C(O)-(CH2)n-, where m is 0 or 1, and n is 0, -(CH2)m-C(O)-NR10-(CH2)n-, where m is 0 or 1, and n is 0, 1 or 2, -(CH2)m-, where m is 1; M is 1) hydrogen atom, 2) 6-14-member aryl, and other radicals referred to in point 1 of the claim; R3 is 1) hydrogen atom, 2) halogen atom, 3) -(C1-C4)alkyl, where alkyl is non-substituted, and other radicals referred to in point 1 of the claim; R11 and R12 are independently the same or different and are 1) hyfrogen atom, 2) -(C1-C6)alkyl, where alkyl is non-substituted or monosubstituted by R13, and other radicals referred to in point 1 of the claim; or R11 and R12 can form 4-8-member monocyclic heterocyclic ring together with nitrogen atoms to which they are linked, and beside the nitrogen atom the ring can include one or two similar or different ring heteroatoms selected out of oxygen, sulfur and nitrogen; where the said heterocyclic ring is independently non-substituted or mono-, disubstituted by R13; R13 is halogen, =O, -OH, -CF3, -(C3-C8)cycloalkyl, -(C0-C3)alkylene-O-R10; R10 is hydrogen, -(C1-C6)alkyl; R15 and R16 are independently hydrogen, -(C1-C6)alkyl; R17 is -(C1-C6)alkyl, -(C3-C8)cycloalkyl; in all stereoisomer forms and their mixes at any ratio, and physiologically tolerable salts. Compounds of the formula I are reversible inhibitors of enzyme factor Xa (FXa) and/or factor VIIa (FVIIa) of blood clotting, and can be generally applied in states accompanied by undesirable factor Xa and/or factor VIla activity, or supposing factor Xa and/or factor VIla inhibition for treatment or prevention. In addition, invention concerns methods of obtaining compounds of the formula I, their application as agents in pharmaceutical compositions.

EFFECT: obtaining compounds applicable as agents in pharmaceutical compositions.

19 cl, 1 tbl, 169 ex

FIELD: chemistry.

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

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

25 cl, 28 tbl, 243 ex

FIELD: chemistry.

SUBSTANCE: description is given of a lactam-containing compound-derivative of tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide with formula I , its pharmaceutical salt and pharmaceutical compositions, their content, and their use as Xa factor inhibitors. The given compound can be used for treating thromboembolic diseases.

EFFECT: obtaining a lactam-containing compound, which can be used for treating thromobembolic diseases.

42 cl, 9 tbl, 140 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: claimed invention relates to novel azaheterocycles of general formula 1.1-13 and 2, as well as their pharmaceutically acceptable salts, which possess anti-carcinogenic activity, pharmaceutical composition with their application and combinatorial and focused libraries including novel azaheterocycles. In general formulae 1.1-1.3 and 2.

.

For compounds 1.1-1.3 each of R1a R2a independently on each other represent possibly substituted C1-C6alkyl; each of R1d, R2d, R3d, R4d, R5d, R6d and R7d independently on each other represent substitutes of cyclic system, preferably hydrogen atom, or for compounds 1.1 and 1.3 independently R1d and R2d, R3d and R4d, R5d and R6d together with atoms with which they are bound can form through R1d and R2d, R3d and R4d, R5d and R6d respectively, possibly substituted aromatic cycle, such as benzole, 5-6-member heterocycle which includes, at least, one of heteroatoms, selected from S; or for compounds 1.2 independently R1d and R2d, R3d and R4d, R4d and R5d, R6d and R7d together with atoms with which they are bound can form through R1d and R2d, R3d and R4d, R4d and R5d, R6d and R7d respectively, possibly substituted aromatic cycle, such as benzole, 5-6-member heterocycle which includes, at least, one of heteroatoms, selected from S; for compound 2 R1a represents amino group substitute, excluding hydrogen atom, such as possibly substituted C1-C6alkyl, possibly substituted phenyl; R2a represents possibly substituted C1-C6alkyl; R3a represents amino group substitute, such as hydrogen atom, possibly substituted C1-C6alkyl; Rnd represents one or two substitutes of cyclic system, preferably hydrogen atom, solid line with accompanying it dotted line represent single or double bond.

EFFECT: obtaining novel azaheterocycles and their pharmaceutically acceptable salts, which possess anti-carcinogenic activity.

9 cl, 4 dwg, 3 tbl, 7 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of pyridine [2,3-d] pyrimidine of general formula (I) and their pharmaceutically acceptable salts, which possess properties of KDR and FGFR inhibitors. Compounds can be applied to produce medications for treatment of cancer, for instance, of mammary gland, large intestine, lungs and prostate gland. In general formula (I) , Ar and Ar' independently on each other are selected from group that includes phenyl; phenyl substituted with 1-3 substituents selected from group C1-C4alkyl, hydroxy, halogen, halogen-substituted C1-C4alkyl, C1-C4alkoxy; 6-member nitrogen-containing heteroaryl and 6-member nitrogen-containing heteroaryl substituted with C1-C4alkoxygroup, on condition that Ar standing for heteroaryl does not represent 2-pyridyl, and standing for substituted heteroaryl does not represent substituted 2-pyridyl, R1 is selected from group including phenyl, C1-C10alkyl, C1-C10alkyl independently containing substituents selected from group that includes phenyl, C3-C6cycloalkyl. Invention also relates to intermediate compounds for compounds of general formula (I) and to pharmaceutical compositions.

EFFECT: obtaining derivatives and their pharmaceutically acceptable salts which possess properties of selective KDR and FGFR inhibitors.

21 cl, 2 tbl, 20 ex

FIELD: chemistry.

SUBSTANCE: described is obtaining and pharmaceutical application of substituted derivatives of arylalkane acid of formula I , where ring A, ring B, R1, R2, R3, R4, R5, X, Alk1, Alk2, Ar1 and Ar2 are such as determined in said description. Said compounds, as selective agonists activating (RAPPs) receptors, activated by peroximal proliferator, in particular, RXRs/RAPPs-alfa, RXRs/RAPPs-gamma and RXRs/RAPPs-delta heterodimers, are applied in treatment and/or prevention of type 2 diabetes and connected with it metabolic syndrome, such as hypertension, obesity, insulin-resistence, hyperlipidemia, hyperglycemia, hyperolesterinemia, artheriaslerosis, coronary artery disease, and other cardio-vascular disorders, and possess improved profile of side effects, connected with common RAPPs-gamma agonists.

EFFECT: obtaining compunds, which possess improved profile of side effects, connected with common RAPPs-gamma agonists.

22 cl, 38 ex, 2 tbl, 10 dwg

FIELD: chemistry.

SUBSTANCE: novel compounds are selected from group, consisting of: 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-hydroxymethyl-cyclopropylmethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopentylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl- 4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihudro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4;9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-ethyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide and 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methoxy-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraazabenzo[f]azulene-9-carbonyl)-benzylamide. Invention also relates to pharmaceutical composition and to application of compounds of general formula 1.

EFFECT: obtaining novel biologically active compounds and based on them pharmaceutical composition, possessing antagonistic activity with respect to vasopressin receptors.

60 cl, 153 ex

FIELD: chemistry.

SUBSTANCE: in general formula I

R1 is phenyl or 5-6-member heterocycle, containing one N atom and/or one O atom; R2 is imidazole or annelated imidazole, selected from group, including a), b), c), d) and e); and R3 stands for hydrogen, phenyl, 2,3-dihydrobenzo[1,4]dioxin-6-yl, benzo[b]thiophen-3-yl, 3-methylbenzo[b] thiophen-2-yl, thiophen-2-yl or thiophen-2-ylmethyl, R4 is hydrogen or lower alkyl, R5 is hydrogen, lower alkyl, halogen, morpholinyl, -NR'R", piperydinyl, optionally substituted with hydroxy-group, or is pyrrolidin-1-yl; R6 is hydrogen or -(CH2)nO-lower alkyl, R7 is hydrogen, -C(O)O-lower alkyl, -C(O)-C6H4-halogen, -C(O)-C6H4-lower alkyl, -C(O)-lower alkyl, -C(O)-cycloalkyl, -C(O)-NR'R", -C(O)-(CH2)nO-lower alkyl, -S(O)2-lower alkyl, -(CH2)nO-lower alkyl, -C(O)-pyridin-4-yl, whose ring can contain as substituents lower alkyl, halogen-lower alkyl or pyrrolidin-1-ylmethyl or is -(CH2)n-C(O)-NR'R"; R'/R" independently on each other stand for hydrogen, lower alkyl or -(CH2)n-tetrahydropyran-4-yl, X is -CH2-, -NR'''- or -O-; R''' is hydrogen, -C(O)-lower alkyl, -C(O)O-lower alkyl, -C(O)-C6H4CH3 or benzyl; n is 1 or 2.

EFFECT: increase of composition and treatment method efficiency.

14 cl, 56 ex

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: chemistry.

SUBSTANCE: in substituted with carbamate groups pyrazolpyridines of general formula (I): R1 stands for group -NR3C(=O)OR4, R2 stands for hydrogen atom or NH2, R3 stands for hydrogen atom or alkyl group with number of carbon atoms from one to four, R4 stands for alkyl group with number of carbon atoms from one to six, as well as to their salt, isomers and hydrates; to methods of their obtaining, medication based on them, as well as to application of said compounds for manufacturing medications for cardio-vascular diseases.

EFFECT: useful biological properties of compounds.

13 cl, 9 ex, 1 tbl

FIELD: chemistry.

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

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

25 cl, 28 tbl, 243 ex

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