Malononitryl derivatives and their application

FIELD: chemistry.

SUBSTANCE: invention relates to novel malononitryl derivatives of formula (I), which can be applied to fight pest insects. In formula (I) R1 represents hydrogen atom; R2 represents hydrogen atom; R represents hydrogen atom; R4 represents C1-C5-alkyl group substituted with at least one halogen atom, C2-C5-alkenyl group; R5 represents hydrogen atom, halogen atom, C1-C5-alkyl group; at least one of X1, X2 and X3 values represents CR6, the other represent nitrogen atoms; R represents hydrogen atom, halogen atom, cyanogroup, nitrogroup, formyl group, C1-C5-alkyl group optionally substituted with at least one halogen atom, C1-C5-alkyltiogroup, substituted with at least one halogen atom, C2-C6-alkylcarbonyl group substituted with at east one halogen atom, C2-C5-alkoxycarbonyl group or group (CH2)mQ, where m = 0, and Q stands for phenyl; and in case when one of R5 and R6 is bonded with two atoms in adjacent positions or two R6 are bonded with two atoms in adjacent positions, they can be bonded to each other in end positions with formation of C2-C6-alkandiyl group, or C4-C6-alkenediyl group. Invention also relates to composition and method used to fight pest-insects.

EFFECT: obtaining novel malononitryl derivatives of formula (I), which can be applied to fight pest-insects.

11 cl, 90 ex

 

The present invention relates to a derivative of malononitrile having the five-membered ring containing a nitrogen atom, and its application.

Developed and proposed for the practical application of compounds with pesticidal activity.

The purpose of this invention is to provide compounds with excellent activity against pests, pesticide composition comprising the said compound as an active ingredient, and a method of pest control application mentioned connection.

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

where in the formula

R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkinyl the th group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

or R3and R4are connected to each other in extreme positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom, or C4-C6-allendales group, optionally substituted by at least one halogen atom;

each of X1X2and X3represents a nitrogen atom or CR6;

each of R5and R6represents a halogen atom, a cyano, a nitro-group, a hydroxyl group, mercaptopropyl, formyl group, a group of SF5, carboxyl group, C1-C5-alkyl group, optionally substituted by at least one the volume of halogen, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C3-C6-alkenylacyl, optionally substituted by at least one halogen atom, C3-C6-alkyloxy, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, C3-C5-altertekhnogrupp, optionally substituted by at least one halogen atom, C3-C5-alinytjara, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C2-C6-alkylcarboxylic group, optionally substituted by at least one halogen atom, C2-C5-alkoxycarbonyl group, optionally substituted by at least one halogen atom, a group labeled

NR10R11the group designation is s(=X 5)NR12NR13, a group labeled (CH2)mQ, the group denoted by C(=NOR17R18or a hydrogen atom;

when one of R5and R6associated with two atoms in adjacent positions, or two R6associated with two atoms in adjacent positions they may be connected with each other in extreme positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom, or C4-C6-allendales group, and in this case, at least one methylene group specified alkadienes group or specified allendales group may be replaced by an oxygen atom or a sulfur atom or a group NR7;

R7represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C3-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C3-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, C2-C6-alkylcarboxylic group, optionally substituted by at least one halogen atom, C2-C5-alkoxycarbonyl group, optionally substituted by at least one the volume of halogen, or a hydrogen atom;

each of R10and R11represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C3-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C3-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, (C1-C5-alkoxygroup, optionally substituted by at least one halogen atom)-C1-C3-alkyl group, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C2-C6-alkylcarboxylic group, optionally substituted by at least one halogen atom, C2-C5-alkoxycarbonyl group, optionally substituted by at least one halogen atom, or a hydrogen atom;

each of R12and R13represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C3-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C3-C5-alkylamino group, optionally substituted by at least one the m a halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, a group labeled (CH2)mQ or a hydrogen atom;

or R12and R13are connected to each other in their limit positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom, or C4-C6-allendales group, optionally substituted by at least one halogen atom;

each of R17and R18represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C3-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C3-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, a group labeled (CH2)mQ or a hydrogen atom;

Q represents an aryl group, optionally substituted by at least one of R14;

each of R14represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted, m is Nisha least one halogen atom or at least one C1-C3 alkyl group, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, C3-C5-altertekhnogrupp, optionally substituted by at least one halogen atom, C3-C5-alinytjara, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one a halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C2-C6-alkylcarboxylic group, optionally substituted by at least one halogen atom, C2-C5-alkoxycarbonyl group, optionally substituted by at least one halogen atom, or halogen atom;

m is an integer from 0 to 5;

X5represents an oxygen atom or a sulfur atom.

The specified derived malononitrile called hereinafter "compound of the present invention". The present invention further provides a pesticide composition comprising an effective amount of the compounds of the present invention and a carrier, a method of combating pests comprising applying an effective amount of the compounds of the present invention to pests and is and habitats of pests, and the use of compounds of the present invention for pest control.

In the present invention albandeira group is a group having a free valence on two different carbon atoms contained in the saturated hydrocarbon chain and albandeira group is a group having a free valence on two different carbon atoms contained in the hydrocarbon chain, having one or two double bonds.

In the present invention the alkyl fluoride group is an alkyl group which is substituted by one or more fluorine atoms, the term "C1-C6" means the total number of carbon atoms, which contains every such Deputy.

In the compound of the present invention C1-C5-alkyl group, optionally substituted by at least one halogen atom represented by R1and R2includes, for example, C1-C3-alkyl group, optionally substituted by at least one halogen atom, such as methyl group, ethyl group, through the group, 1-mtilatila group (hereinafter may be referred to as ISO-propyl group), chloromethylene group, permetrina group, deformational group, triptorelin group, 2,2,2-triptorelin group and 1,1,2,2-tetrafluoroethylene group, and 1,1-dimethylethylene group (hereinafter m what may be called tert-butilkoi group);

C2-C5-Alchemilla group, optionally substituted by at least one halogen atom includes, for example, vinyl group, a 2,2-differenly group, 1,2,2-triptorelin group, 1-propenyloxy group and 2-propenyloxy group;

C2-C5-Alchemilla group, optionally substituted by at least one halogen atom includes, for example, etinilnoy group, 1-propenyloxy group, 2-propenyloxy group and 3,3,3-Cryptor-1-propenyloxy group.

C1-C5-Alkoxygroup, optionally substituted by at least one halogen atom represented by R2includes, for example, C1-C3-alkoxygroup, optionally substituted by at least one halogen atom, such as methoxy group, ethoxypropan, 1-methylethoxy, tripterocarpa, dipterocarp, 2,2,2-triftoratsetata and 1,1,2,2-tetracarboxylate; and butoxypropan.

C1-C5-Alkyl group, optionally substituted by at least one halogen atom represented by R3and R4includes, for example, methyl group, ethyl group, 1-methylamino group, 2-methylpropyloxy group, through the group, boutelou group, 3-methylbutyl group, 2,2-dimethylpropylene group, formeterol group, chloromethylene group, 2,2-deperately group, 2,2-dichloroethylene group, 3,3-deferrability group, 3,3-dichlorethylene is the Rupp, triptorelin group, trichlorethylene group, 2,2,2-triptorelin group, 2,2,2-trichlorethylene group, 3,3,3-triptorelin group, 3,3,3-trichloropropane group, 2,2-deferrability group, 3,3-deformational group, 1-bromo-2,2,2-triptorelin group, 1-chloro-2,2,2-triptorelin group, 1,2,2,2-tetrafluorethylene group, panafcortelone group, 2,2,3,3,3-pentafluoropropyl group, 1,1,2,2-tetrafluoroethylene group and 2,2,3,3-tetrafluoropropyl group;

C2-C5-Alchemilla group, optionally substituted by at least one halogen atom includes, for example, vinyl group, allyl group, 1-propenyloxy group, 3-butenyloxy group, 2-methyl-1-propenyloxy group, 3-methyl-2-butenyloxy group, 3-pentanediol group, 4-pentanediol group, 3-methyl-3-butenyloxy group, 4-methyl-3-pentanediol group, 1-chloraniline group, 2-chloraniline group, 1-forfinally group 2-forfinally group, 2,2-dichlorovinyl group, 2,2-dibromovinyl group, 2,2-differenly group, 1,2,2-triptorelin group, 1-(trifluoromethyl)vinyl group, 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-propenyloxy group, 2-(trifluoromethyl)-2-propenyloxy group, 2,3,3,3-titrator-1-propenyloxy group, 1,2,3,3,3-pendaftar-1-propenyloxy group is, 3,4,4-Cryptor-3-butenyloxy group, 3,4,4,4-titrator-2-butenyloxy group, 2,3,4,4,4-pendaftar-2-butenyloxy group and 4,5,5-Cryptor-4-pentanediol group;

C2-C5-Alchemilla group, optionally substituted by at least one halogen atom includes, for example, etinilnoy group, 1-propenyloxy group, 2-propenyloxy group, 1-butenyloxy group, 3-methyl-1-butenyloxy group, 2-chloro-1-propenyloxy group, 3-chloro-2-propenyloxy group, 3,3,3-Cryptor-1-propenyloxy group and 4,4,4-Cryptor-2-butenyloxy group;

C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group includes, for example, cyclopropyl group, 2,2-dichlorocyclopentane group, 2,2-divorcecelebration group, 2,2,3,3-tetrafluorochloroethane group, 2,2-dichlororesorcinol group, 2,2-diverticulitishow group, 2,2,3,3-tetrafluorochloroethane group, cyclobutyl group, cyclopentyl group and tsiklogeksilnogo group;

C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom includes, for example, 2-fluoro-2-cyclopentenyl group.

C2-C6-Alcantarilla group, optionally substituted by at least one halogen atom and formed by linking R3and R4includes, for example, ethylene group, a propyl is a new group, trimethylene group and tetramethylene group;

C4-C6-alcantarilla group, optionally substituted by at least one halogen atom and formed by linking R3and R4includes, for example, 2-butenylamine group and 2-pentesilea group.

The halogen atom represented by R5, R6and R14includes fluorine atom, chlorine atom, bromine atom and iodine atom.

C1-C5-Alkyl group, optionally substituted by at least one halogen atom and represented by R5, R6, R7, R10, R11, R12, R13, R14, R17and R18includes, for example, methyl group, ethyl group, 1-methylamino group, 1-ethylethylene group, 1,1-dimethylethylene group, n-sawn group, 1-methylpropyl group, 1-ethylpropyl group, 1,1-dimethylpropyl group, 2,2-dimethylpropyl group, 1,2-dimethylpropylene group, 1,1,2-trimethylpropyl group, n-boutelou group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, n-pentelow group, formeterol group, chloromethylene group, bromatology group, codmedicine group, deformational group, chlorodifluoromethyl group, bromodifluoromethyl group, triptorelin group, dichloromethylene group, trichlorethylene group, 1-chlorethylene group, 1-bromatology groups who, 1-codmedicine group, 1-foretelling group, 2-chloraniline group, 2-bromatology group, 2-codmedicine group, 2-foretelling group, 2,2-deperately group, 2,2,2-triptorelin group, 2,2,2-trichlorethylene group, panafcortelone group, 2,2,2-Cryptor-1-chlorethylene group, 3-forproperty group, 3-chloropropylene group, 1-fluoro-1-methylamino group, 1-chloro-1-methylamino group, 2-chloro-1,1-dimethylethylene group, 2-fluoro-1,1-dimethylethylene group, heptafluoropropyl group, a 1,1,2,2,3,3-hexaplar-n-through group, 4-chlorobutanol group, 4-terbutaline group, 5-chloraniline group and 5-formentino group.

C2-C5-Alchemilla group, optionally substituted by at least one halogen atom and represented by R5or R6includes, for example, vinyl group, 1-methylvinyl group, 1-propenyloxy group, 1-methyl-1-propenyloxy group, 2-methyl-1-propenyloxy group, 1,2-dimethyl-1-propenyloxy group, 2-propenyloxy group, 1-methyl-2-propenyloxy group, 2-methyl-2-propenyloxy group, 1,1-dimethyl-2-propenyloxy group, 1,2-dimethyl-2-propenyloxy group and 2,2-differenly group, 2-chloro-2-propenyloxy group, 2,2-dichloro-2-propenyloxy group, 2-bromo-2-propenyloxy group, 2,2-dibromo-2-propenyloxy group, 2-fluoro-2-propenyloxy group and 2,2-debtor-2-propenyloxy group.

C3-C5-Alchemilla group, n is necessarily substituted, at least one halogen atom and represented by R7, R10, R11, R12, R13, R17and R18includes, for example, 1-methylvinyl group, 1-propenyloxy group, 1-methyl-1-propenyloxy group, 2-methyl-1-propenyloxy group, 1,2-dimethyl-1-propenyloxy group, 2-propenyloxy group, 1-methyl-2-propenyloxy group, 2-methyl-2-propenyloxy group, 1,1-dimethyl-2-propenyloxy group, 1,2-dimethyl-2-propenyloxy group, 2-chloro-2-propenyloxy group, 2,2-dichloro-2-propenyloxy group 2-bromo-2-propenyloxy group, 2,2-dibromo-2-propenyloxy group, 2-fluoro-2-propenyloxy group and 2,2-debtor-2-propenyloxy group.

C2-C5-Alchemilla group, optionally substituted by at least one halogen atom and represented by R5or R6includes, for example, etinilnoy group, 1-propenyloxy group, 2-propenyloxy group and 3,3,3-Cryptor-1-propenyloxy group.

C3-C5-Alchemilla group, optionally substituted by at least one halogen atom and represented by R7, R10, R11, R12, R13, R17and R18includes, for example, 1-propenyloxy group, 2-propenyloxy group and 3,3,3-Cryptor-1-propenyloxy group.

C3-C6-Cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group and presents Rsup> 5, R6, R7, R10, R11, R12, R13, R14, R17and R18includes, for example, cyclopropyl group, 1-methylcyclopropyl group, 2,2-dichlorocyclopentane group, 2,2-dichloro-1-methylcyclopropyl group, 2,2-divorcecelebration group, 2,2-debtor-1-methylcyclopropyl group, cyclobutyl group, cyclopentyl group and tsiklogeksilnogo group.

C1-C5-Alkoxygroup, optionally substituted by at least one halogen atom and represented by R5, R6and R14includes, for example, a methoxy group, ethoxypropan, propoxylate, cryptometer, bromodifluoroacetate, dipterocarp, Hortiflorexpo, pentafluoropropyl, 2,2,2-triptracker and 1,1,2,2-tetrafluoroethoxy.

C3-C6-Alkenylacyl, optionally substituted by at least one halogen atom and represented by R5and R6includes, for example, 1-propenyloxy, 2-propenyloxy and 2,2-debtor-2-propenyloxy.

C3-C6-Alkyloxy, optionally substituted by at least one halogen atom and represented by R5and R6includes, for example, 2-propenyloxy, 2-butenyloxy and 3,3,3-Cryptor-1-propenyloxy.

(C1-C5-Alkoxygroup, optionally substituted by at least one atom of Galaga is a)C1-C3-alkyl group, presents R10and R11includes, for example, methoxymethyl group, ethoxymethyl group, 1-methoxyamino group, 1-ethoxyethylene group and triftormetilfullerenov group.

C1-C5-Allylthiourea, optionally substituted by at least one halogen atom and represented by R5, R6and R14includes, for example, methylthiourea, ethylthiourea, triptoreline, chlordiftormethane, bromodifluoromethane, dibrompropamidine, 2,2,2-triptoreline, 1,1,2,2-tetrafluorethylene and pentafluoropropyl.

C3-C5-Alchemistjoshua, optionally substituted by at least one halogen atom and represented by R5, R6and R14includes, for example, 1-PropertyGroup, 2-PropertyGroup and 2,2-debtor-2-PropertyGroup.

C3-C5-Alinytjara, optionally substituted by at least one halogen atom and represented by R5, R6and R14includes, for example, 2-propylthiourea, 2-BUSINESSEUROPE and 3,3,3-Cryptor-1-propylthiourea.

C1-C5-Alkylsulfonyl group, optionally substituted by at least one halogen atom and represented by R5, R6, R10, R11and R14includes, for example, methylsulfinyl group and trifloromethyl group.

C1-C5-Alkylsulfonyl the Naya group, optionally substituted by at least one halogen atom and represented by R5, R6, R10, R11and R14includes, for example, methylsulfonyl group and triftormetilfullerenov group.

C2-C6-Alkylcarboxylic group, optionally substituted by at least one halogen atom and represented by R5, R6, R7, R10, R11and R14includes, for example, acetyl group, propionyl group, 2,2-dimethylpropylene group and trifluoracetyl group.

C2-C5-Alkoxycarbonyl group represented by R5, R6, R7, R10, R11and R14includes, for example, methoxycarbonyl group, ethoxycarbonyl group, 1-methylethoxyethanol group and tert-butoxycarbonyl group.

In the case when R5and R6bound to atoms in adjacent positions, or two R6bound to atoms in adjacent positions, they are connected to each other at the end of their positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom and includes, for example, propylene group, trimethylene group and tetramethylene group; C4-C6-allendales group, optionally substituted by at least one halogen atom and includes, for example, 2-butenylamine group and pentesilea group.

C2-C6-Alcantarilla group, optionally substituted by at least one halogen atom and represented by the combination of R12and R13includes, for example, ethylene group, propylene group, trimethylene group and tetramethylene group; C4-C6-alcantarilla group, optionally substituted by at least one halogen atom includes, for example, 2-butenylamine group and 2-pentesilea group.

Compounds of the present invention include, for example, the following connections:

derived malononitrile formula (I)in which R1represents a hydrogen atom;

derived malononitrile formula (I)in which R2represents a methyl group;

derived malononitrile formula (I)in which R1and R2represent hydrogen atoms;

derived malononitrile formula (I)in which R1represents a hydrogen atom and R2represents a methyl group;

derived malononitrile formula (I)in which R3represents a hydrogen atom;

derived malononitrile formula (I)in which R4represents a C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom;

derived malononitrile formula (I)in which R4represents a vinyl group;

derived malononitrile formula (I)in which R4is a 2-propenyloxy group;

derived malononitrile formula (I)in which R4represents 2,2-differenly group;

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

derived malononitrile formula (I)in which R4represents 3,3-debtor-2-propenyloxy group;

derived malononitrile formula (I)in which R4is a 2,3,3-Cryptor-2-propenyloxy group;

derived malononitrile formula (I)in which R4is a 3,3,3-Cryptor-1-propenyloxy group;

derived malononitrile formula (I)in which R4represents a C2-C5-halogenalkyls group, optionally substituted by at least one halogen atom;

derived malononitrile formula (I)in which R4represents a C1-C5-alkyl fluoride group;

derived malononitrile formula (I)in which R4represents pharmacylow group;

derived malononitrile formula (I)in which R4represents 2,2-deperately group;

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

derived malononitrile of formula I, in which R4represents panafcortelone group;

derived malononitrile formula (I)in which R4is a 3,3,3-triptorelin group;

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

derived malononitrile formula (I)in which R4represents C3-C6-cycloalkyl group;

derived malononitrile formula (I)in which R4represents 2,2-dichlorocyclopentane group;

derived malononitrile formula (I)in which R4represents cyclopropyl group;

derived malononitrile formula (I)in which R4represents cyclobutyl group;

derived malononitrile formula (I)in which R3represents a hydrogen atom and R4represents a vinyl group and a 2-propenyloxy group;

derived malononitrile formula (I)in which R3represents a hydrogen atom and R4represents 2,2-differenly group, 1-(trifluoromethyl)vinyl group, 3,3-debtor-2-propenyloxy group, 2,3,3-Cryptor-2-propenyloxy group or 3,3,3-Cryptor-1-propenyloxy group;

derived malononitrile formula (I)in which R3represents a hydrogen atom and R4is format the optimum group, 2,2-deperately group, 2,2,2-triptorelin group, 1,1,2,2,2-panafcortelone group, 3,3,3-triptorelin group or 2,2,3,3,3-pentafluoropropyl group;

derived malononitrile formula (I)in which R3represents a hydrogen atom and R4represents cyclopropyl group, cyclobutyl group or 2,2-dichlorocyclopentane group;

derived malononitrile formula (I)in which R1, R2and R3represent hydrogen atoms, and R4represents a vinyl group or a 2-propenyloxy group;

derived malononitrile formula (I)in which R1, R2and R3represent hydrogen atoms, and R4represents 2,2-differenly group, 1-(trifluoromethyl)vinyl group, 3,3-debtor-2-propenyloxy group, 2,3,3-Cryptor-2-propenyloxy group or 3,3,3-Cryptor-1-propenyloxy group;

derived malononitrile formula (I)in which R1and R3represent hydrogen atoms, R2represents a methyl group and R4represents 2,2-differenly group or 1-(trifluoromethyl)vinyl group, 3,3-debtor-2-propenyloxy group, 2,3,3-Cryptor-2-propenyloxy group or 3,3,3-Cryptor-1-propenyloxy group;

derived malononitrile formula (I)in which R1, R2and R3represent the volumes of hydrogen and R 4represents pharmacylow group, 2,2-deperately group, 2,2,2-triptorelin group, panafcortelone group, 3,3,3-triptorelin group or 2,2,3,3,3-pentafluoropropyl group;

derived malononitrile formula (I)in which R1and R3represent hydrogen atoms, R2represents a methyl group and R4represents pharmacylow group, 2,2-deperately group, 2,2,2-triptorelin group, panafcortelone group, 3,3,3-triptorelin group or 2,2,3,3,3-pentafluoropropyl group;

derived malononitrile formula (I)in which R1, R2and R3represent hydrogen atoms, and R4represents cyclopropyl group, cyclobutyl group or 2,2-dichlorocyclopentane group;

derived malononitrile formula (I), in which each of X1X2and X3represents CR6;

derived malononitrile formula (I)in which X1represents a nitrogen atom and each of X2and X3represents CR6;

derived malononitrile formula (I)in which X2represents a nitrogen atom and each of X1and X3represents CR6;

derived malononitrile formula (I)in which X3represents a nitrogen atom and each IZH 1and X2represents CR6;

derived malononitrile formula (I)in which X1and X2represent nitrogen atoms and X3represents CR6;

derived malononitrile formula (I)in which X1and X3represent nitrogen atoms and X2represents CR6;

derived malononitrile formula (I)in which X1X2and X3are nitrogen atoms;

derived malononitrile formula (I)in which X3represents CR6and

R6represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted atom(s), halogen, or C2-C5-alkylamino group, optionally substituted by at least one halogen atom;

derived malononitrile formula (I)in which X3represents CR6and

R6represents an ethyl group;

derived malononitrile formula (I)in which X3represents CR6and

R6is a 1-methylamino group;

derived malononitrile formula (I)in which X3represents CR6and

R6represents a 1,1-dimethylethylene group;

derived malononitrile formula is (I), in which X3represents CR6and

R6represents 2,2-dimethylpropylene group;

derived malononitrile formula (I)in which X3represents CR6and

R6represents triptorelin group;

derived malononitrile formula (I)in which X3represents CR6and

R6represents panafcortelone group;

derived malononitrile formula (I)in which X3represents CR6and

R6is a 1-methylvinyl group;

derived malononitrile formula (I)in which X3represents CR6and

R6represents etinilnoy group;

derived malononitrile formula (I)in which X3represents CR6and

R6represents C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom;

derived malononitrile formula (I)in which X3represents CR6and

R6represents cyclopropyl group;

derived malononitrile formula (I)in which X3represents CR6and

R6is a 1-methylcyclopropyl group;

derived malononitrile formula (I)in which X3is the th CR 6and

R6represents a C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C3-C6-alkenylacyl, optionally substituted by at least one halogen atom, or a C3-C6-alkyloxy, optionally substituted by at least one halogen atom;

derived malononitrile formula (I)in which X3represents CR6and

R6is propargyloxy;

derived malononitrile formula (I)in which X3represents CR6and

R6is a 2-butenyloxy;

derived malononitrile formula (I)in which X3represents CR6and

R6is a 3-butenyloxy;

derived malononitrile formula (I)in which X3represents CR6and

R6represents a C1-C5-allylthiourea, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted atom(s), halogen, or C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom;

derived malononitrile formula (I)in which X3represents CR6and

R6is methylthiourea;

derived malonamic the La formula (I), in which X3represents CR6and

R6is triptoreline;

derived malononitrile formula (I)in which X3represents CR6and

R6is propargylation;

derived malononitrile formula (I)in which X3represents CR6and

R6represents methylsulfinyl group;

derived malononitrile formula (I)in which X3represents CR6and

R6represents trifloromethyl group;

derived malononitrile formula (I)in which X3represents CR6and

R6represents methylsulfonyl group;

derived malononitrile formula (I)in which X3represents CR6and

R6represents cyano;

derived malononitrile formula (I)in which X3represents CR6and

R6represents a halogen atom;

derived malononitrile formula (I)in which X3represents CR6and

R6represents a bromine atom;

derived malononitrile formula (I)in which X3represents CR6and

R6represents a chlorine atom;

derived malononitrile of formula I, in which X3represents CR6and

R6represents a fluorine atom;

derived malononitrile formula (I)in which X3represents CR6and

R6is a nitro-group;

derived malononitrile formula (I)in which R1represents a hydrogen atom and R2represents C1-C3-alkyl group, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile formula (I)in which R1represents C1-C3-alkyl group, optionally substituted by at least one halogen atom, or hydrogen atom, and R2represents C1-C3-alkyl group, optionally substituted by at least one halogen atom, C1-C3-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

derived malononitrile formula (I), in which each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted, n is at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, or R3and R4are connected to each other in their limit positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom;

derived malononitrile formula (I)in which R1represents a hydrogen atom, R2represents C1-C3-alkyl group, optionally substituted by at least one halogen atom, or a hydrogen atom, each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, or R3and R4are connected to each other in their limit positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom,

derived malononitrile formula (I)in which R1represents C1-C3-alkyl group, optionally substituted by at least one halogen atom, or a hydrogen atom, R2represents C1-C3-alkyl group, optionally substituted by at least one halogen atom, C1-C3-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom, each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, or R3and R4are connected to each other in their limit positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom;

derived malononitrile formula (I)in which R3not only is em a hydrogen atom, R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or R3and R4are connected to each other in their limit positions with the formation of C2-C6-alkadienes group;

derived malononitrile formula (I)in which R1represents a hydrogen atom, R2represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, or a hydrogen atom, R3represents a hydrogen atom, R4represents C1-C3-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or R3and R4are connected to each other in their limit positions with the formation of C2-C6-alkadienes group;

derived malononitrile formula (I)in which R1represents C1-C3-alkyl group, optionally substituted by at least one halogen atom, or a hydrogen atom, R2is own the th C1-C3-alkyl group, optionally substituted by at least one halogen atom, C1-C3-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, cyano or a hydrogen atom, R3represents a hydrogen atom, R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or R3and R4are connected to each other in their limit positions with the formation of C2-C6-alkadienes group;

derived malononitrile represented by formula (I-1),

where in the formula

R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, n is necessarily substituted, at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

or R3and R4are connected to each other in their limit positions with the formation of C4-C6-alkadienes group, optionally substituted by at least one halogen atom, or C4-C6-allendales group, optionally substituted by at least one halogen atom;

each of R5and R6-1represents a halogen atom, a cyano, a nitro-group, hydroximino the group, mercaptopropyl, formyl group, a group of SF5, carboxyl group, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C3-C6-alkenylacyl, optionally substituted by at least one halogen atom, C3-C6-alkyloxy, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, C3-C5-altertekhnogrupp, optionally substituted by at least one halogen atom, C3-C5-alinytjara, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C2-C6-alkylcarboxylic group, optionally substituted by at least one halogen atom is, C2-C5-alkoxycarbonyl group, optionally substituted by at least one halogen atom, phenyl group, or a hydrogen atom;

derived malononitrile formula (I-1), in which R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted, less is th least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

or R3and R4are connected to each other in their limit positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom or C4-C6-allendales group, optionally substituted by at least one halogen atom;

R5represents a hydrogen atom;

and R6-1represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile formula (I-1), in which R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted, at the ore, one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

R5represents a hydrogen atom;

and R6-1represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile (I-1), in which R1, R2, R3and R5represent hydrogen atoms;

R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, or a C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom;

and R6-1represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile formula (I-1), in which R1, R2, R3and R5represent hydrogen atoms;

R4represents a 2,2,2-triptorelin group or vinyl group;

and R6-1represents a hydrogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile represented by formula (I-2),

where in the formula

R1is particularly the C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

or R3and R4connect drugs other in their limit positions with the formation of C4-C6-alkadienes group, optionally substituted by at least one halogen atom, or C4-C6-allendales group, optionally substituted by at least one halogen atom;

each of R5and R6-1and R6-2represents a halogen atom, a cyano, a nitro-group, a hydroxyl group, mercaptopropyl, formyl group, a group

SF5, carboxyl group, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C3-C6-alkenylacyl, optionally substituted by at least one halogen atom, C3-C6-alkyloxy, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, C3-C5-altertekhnogrupp, optionally substituted by at least one halogen atom, C3-C5-alinytjara, optionally substituted by at least one atom of GoLoG is on, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C2-C6-alkylcarboxylic group, optionally substituted by at least one halogen atom, C2-C5-alkoxycarbonyl group, optionally substituted by at least one halogen atom, phenyl group, or a hydrogen atom;

derived malononitrile formula (I-2), in which

R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optional what about substituted, at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

or R3and R4are connected to each other in their limit positions with the formation of C4-C6-alkadienes group, optionally substituted by at least one halogen atom, or C4-C6-allendales group, optionally substituted by at least one halogen atom;

R5represents a hydrogen atom;

and each of R6-1and R6-2represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile formula (I-2), in which

R1represents a C1-C5-alkyl group, optionally substituted by at measures which, one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

R5represents a hydrogen atom;

and each of R6-1and R6-2PR is dstanley a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile formula (I-2), in which

R1, R2, R3and R5represent hydrogen atoms;

R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, or a C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom,

and each of R6-1and R6-2represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile formula (I-2), in which

R1, R2, R3and R5represent hydrogen atoms;

R4represents a 2,2,2-triptorelin group or vinyl group;

and each of R6-1and R6-2represents a halogen atom, C1-C5-alkyl group, optionally zameshano is, at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile represented by formula (I-3),

where in the formula

R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one atom of GoLoG is on, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

or R3and R4are connected to each other in their limit positions with the formation of C4-C6-alkadienes group, optionally substituted by at least one halogen atom, or C4-C6-allendales group, optionally substituted by at least one halogen atom;

each of R5and R6-1and R6-2represents a halogen atom, a cyano, a nitro-group, a hydroxyl group, mercaptopropyl, formyl group, a group

SF5, carboxyl group, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, C1-C5-alkoxygroup, optionally substituted, minicamera, one halogen atom, C3-C6-alkenylacyl, optionally substituted by at least one halogen atom, C3-C6-alkyloxy, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, C3-C5-altertekhnogrupp, optionally substituted by at least one halogen atom, C3-C5-alinytjara, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted, least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C2-C6-alkylcarboxylic group, optionally substituted by at least one halogen atom, C2-C5-alkoxycarbonyl group, optionally substituted by at least one halogen atom, phenyl group, or a hydrogen atom;

derived malononitrile represented by formula (I-3), in which

R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2present is employed, a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

or R3and R4are connected to each other in their limit positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom, or C4-C6-allendales group, optionally substituted by at least one halogen atom;

R5represents a hydrogen atom;

and each of R6-1and R6-2 represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile represented by formula (I-3), in which

R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

R5represents a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one atom of GoLoG is on, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom;

and each of R6-1and R6-2represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile formula (I-3), in which

R1, R2, R3and R5represent hydrogen atoms;

R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, or a C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom;

and each of R6-1and R6-2represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxy is the SCP, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile formula (I-3), in which

R1, R2, R3and R5represent hydrogen atoms;

R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, or a C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom;

R6-1represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

and R6-2represents a halogen atom or a hydrogen atom;

derived malononitrile formula (I-3), in which

R1, R2, R3and R5represent hydrogen atoms;

R4represents a 2,2,2-triptorelin group or vinyl group;

and each of R6-1and R6-2represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, not battelino substituted, at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile formula (I-3), in which

R1, R2, R3and R5represent hydrogen atoms;

R4represents a 2,2,2-triptorelin group or vinyl group;

R6-1represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

and R6-2represents a halogen atom or a hydrogen atom;

derived malononitrile represented by formula (I-4)

where in the formula

R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-who 5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

or R3and R4are connected to each other in their limit positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom, or C4-C6-allendales group, optionally substituted by at least one halogen atom;

each of R5, R6-1and R6-2represents a halogen atom, a cyano, a nitro-group, a hydroxyl group, mercaptopropyl, formyl group, group is the

SF5, carboxyl group, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C3-C6-alkenylacyl, optionally substituted by at least one halogen atom, C3-C6-alkyloxy, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, C3-C5-altertekhnogrupp, optionally substituted by at least one halogen atom, C3-C5-alinytjara, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C2-C6-alkylcarboxylic group, optionally substituted by at least one halogen atom, C2-C5-alkoxycarbonyl group, it is certainly substituted, at least one halogen atom, phenyl group, or a hydrogen atom;

derived malononitrile represented by formula (I-4), in which

R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at ENISA least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

or R3and R4are connected to each other in their limit positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom, or C4-C6-allendales group, optionally substituted by at least one halogen atom;

R5represents a hydrogen atom;

and each of R6-1and R6-2represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile represented by formula (I-4), in which

R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted, Melsheimer, one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, a cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R5represents a hydrogen atom;

and each of R6-1and R6-2represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

the production is the same of malononitrile formula (I-4), in which

R1, R2, R3and R5represent hydrogen atoms;

R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, or a C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom;

and each of R6-1and R6-2represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom;

derived malononitrile formula (I-4), in which

R1, R2, R3and R5represent hydrogen atoms;

R4represents a 2,2,2-triptorelin group or vinyl group;

and each of R6-1and R6-2represents a halogen atom, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, or a hydrogen atom.

In representations of the compounds of formula (I-1) to formula (I-4) represented

R6-1or R 6-2the halogen atom includes, for example, fluorine atom, chlorine atom and bromine atom;

C1-C5-alkyl group, optionally substituted by at least one halogen atom includes, for example, C1-C5-alkyl fluoride group, such as triptorelin group, 2,2,2-triptorelin group and the like, and alkyl group, which has a branched in the 1-position, such as ISO-propyl group, tert-bucilina group, 1,1-dimethylpropylene group and the like;

C1-C5-alkoxygroup, optionally substituted by at least one halogen atom includes, for example, a methoxy group, ethoxypropan, 1-methylethoxy and the like;

C1-C5-allylthiourea, optionally substituted by at least one halogen atom includes, for example, methylthiourea, ethylthiourea, 1-metilethylchlorophos and the like.

Next will be described a method of obtaining compounds of the present invention.

The compound of the present invention can be obtained, for example, according to the following methods (a method for 1), (getting 2).

(Method of obtaining 1)

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

where in formulas

R1represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol g is the SCP, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, or a hydrogen atom;

R2represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, cyano or a hydrogen atom;

each of R3and R4represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C5-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, C4-C5-cycloalkenyl group, optionally substituted by at least one halogen atom, or a hydrogen atom,

or R3and R4are connected to each other in extreme positions with the formation of C2-C6-alkadienes group, optional C is displaced, at least one halogen atom, or C4-C6-allendales group, optionally substituted by at least one halogen atom;

each of X1X2and X3represents a nitrogen atom or CR6;

each of R5and R6represents a halogen atom, a cyano, a nitro-group, a hydroxyl group, mercaptopropyl, formyl group, a group of SF5, carboxyl group, C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C2-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C3-C6-alkenylacyl, optionally substituted by at least one halogen atom, C3-C6-alkyloxy, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, C3-C5-altertekhnogrupp, optionally substituted by at least one halogen atom, C1-C5-alinytjara, not necessarily for sennou, at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C2-C6-alkylcarboxylic group, optionally substituted by at least one halogen atom, C2-C5-alkoxycarbonyl group, optionally substituted by at least one halogen atom, a group labeled

NR10R11the group denoted by C(=X5)NR12NR13, a group labeled (CH2)mQ, the group denoted by C(=NOR17R18or a hydrogen atom;

when one of R5and R6or two R6associated with two atoms in adjacent positions they may be connected with each other in extreme positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom, or C4-C6-allendales group. And in this case, at least one methylene group specified alkadienes group or specified allendales group may be replaced by an oxygen atom or a sulfur atom or a group NR7;

R7represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C3-C5-alkenylphenol group, not necessarily samewe the ing, at least one halogen atom, C3-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, C2-C6-alkylcarboxylic group, optionally substituted by at least one halogen atom, C2-C5-alkoxycarbonyl group, optionally substituted by at least one halogen atom, or a hydrogen atom;

each of R10and R11represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C3-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C3-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3-alkyl group, (C1-C5-alkoxygroup, optionally substituted by at least one halogen atom)-C1-C3-alkyl group, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C2-C6-alkylcarboxylic group, optional Zam is pregnant at least one halogen atom, C2-C5-alkoxycarbonyl group, optionally substituted by at least one halogen atom, or a hydrogen atom;

each of R12and R13represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C3-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C3-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, a group labeled (CH2)mQ or a hydrogen atom;

or R12and R13are connected to each other at the end of their positions with the formation of C2-C6-alkadienes group, optionally substituted by at least one halogen atom, or C2-C6-allendales group, optionally substituted by at least one halogen atom;

each of R17and R18represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C3-C5-alkenylphenol group, optionally substituted by at least one halogen atom, C3-C5-alkylamino group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl is inuu group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, a group labeled (CH2)mQ or a hydrogen atom;

Q represents an aryl group, optionally substituted by at least one of R14;

each of R14represents a C1-C5-alkyl group, optionally substituted by at least one halogen atom, C3-C6-cycloalkyl group, optionally substituted by at least one halogen atom or at least one C1-C3 alkyl group, C1-C5-alkoxygroup, optionally substituted by at least one halogen atom, C1-C5-allylthiourea, optionally substituted by at least one halogen atom, C3-C5-altertekhnogrupp, optionally substituted by at least one atom of halogen, C3-C5-alinytjara, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C1-C5-alkylsulfonyl group, optionally substituted by at least one halogen atom, C2-C6-alkylcarboxylic group, optionally substituted by at least one halogen atom, C2-C5-alkoxycarbonyl group, optionally substituted by at least one halogen atom, or atom halog is on;

m is an integer from 0 to 5;

X5represents an oxygen atom or a sulfur atom;

E1represents a leaving group such as chlorine atom, bromine atom, iodine atom, methanesulfonyl group, trifloromethyl group, toluensulfonyl group, methysulfonylmethane, triftormetilfullerenov and toluensulfonate and the like.

The reaction is usually carried out in a solvent and in the presence of a base.

The solvent used for the reaction includes, for example, acid amides such as N,N-dimethylformamide and the like; ethers such as diethyl ether, tetrahydrofuran and the like, organic sulfur compounds such as dimethylsulfoxide, sulfolane and the like, halogenated hydrocarbons such as 1,2-dichloroethane, chlorobenzene and the like, aromatic hydrocarbons such as toluene, xylene and the like, and mixtures thereof.

Used for the reaction includes, for example, inorganic bases such as sodium hydride, sodium carbonate, potassium carbonate and the like, alkoxides of alkali metals, such as tert-piperonyl potassium and the like, amides of alkali metals, such as diisopropylamide lithium and the like, and organic bases, such as 4-(dimethylamino)pyridine, 1,4-diazabicyclo[2.2.2]octane 1,8-diazabicyclo[5.4.0]-7-undecene and the like.

The amount of base used for the reaction is usually 1 to 10 mol per 1 mol of compound (a).

The amount of compound (b)used for the reaction is usually 1 to 10 mol per 1 mol of compound (a).

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

After completion of the reaction the compound of the present invention represented by the formula (I), can be identified by carrying out the subsequent processing of the reaction mixture, such as pouring the reaction mixture into water, extraction with an organic solvent followed by concentration of the extract. A dedicated connection of the present invention represented by the formula (I)can, if required, clear, chromatography, recrystallization and the like.

(Method of obtaining 2)

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

where in the formula E1, R1, R2, R3, R4, R5X1X2and X3have the same meanings as described above.

The reaction is usually carried out in a solvent and in the presence of a base.

The solvents used for the reaction include, for example, acid amides such as N,N-dimethylformamide and the like; ethers such as diethyl ether, tetrahydro the furan and the like, organic sulfur compounds such as dimethylsulfoxide, sulfolane and the like, halogenated hydrocarbons such as 1,2-dichloroethane, chlorobenzene and the like, aromatic hydrocarbons such as toluene, xylene and the like, and mixtures thereof.

Used for the reaction includes, for example, inorganic bases such as sodium hydride, sodium carbonate, potassium carbonate and the like, alkoxides of alkali metals, such as tert-piperonyl potassium and the like, amides of alkali metals, such as diisopropylamide lithium and the like, and organic bases, such as 4-(dimethylamino)pyridine, 1,4-diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]-7-undecene and the like.

The amount of base used for the reaction is usually 1 to 10 mol per 1 mol of compound (C).

The number of compounds (d)used for the reaction is usually 1 to 10 mol per 1 mol of compound (C).

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

After completion of the reaction the compound of the present invention represented by the formula (I), can be identified by carrying out the subsequent processing of the reaction mixture, such as pouring the reaction mixture into water, extraction by organic solvent with subsequent conc the requirement of the extract. A dedicated connection of the present invention represented by the formula (I)can, if required, clear, chromatography, recrystallization and the like.

Then you will learn how to obtain the intermediate compound as a reference retrieval method.

(Reference method of obtaining 1)

where in the formula, R1, R2, R5X1X2and X3have the same meanings as described above.

(The first stage)

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

The reaction is usually conducted in a solvent. The solvents used for the reaction include, for example, acid amides such as N,N-dimethylformamide and the like, ethers such as diethyl ether, tetrahydrofuran and the like, halogenated hydrocarbons such as chloroform, 1,2-dichloroethane, chlorobenzene and the like, aromatic hydrocarbons such as toluene, xylene and the like, alcohols such as methanol, ethanol, isopropanol and the like, and mixtures thereof.

The reaction, if required, is carried out in the presence of a base, and the base used for the reaction include, for example, tetrabutylammonium hydroxide and the like.

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

<> The number of malononitrile used for the reaction is usually 1 to 10 mol per 1 mol of compound (e).

The reaction temperature is usually in the range from -20 to 100°C., and the reaction time is usually in the range from 1 to 24 hours.

The reaction, if necessary, can be performed with removal of water formed during the reaction, from the reaction system.

After completion of the reaction, the compound (f) can be distinguished by carrying out the subsequent processing of the reaction mixture, such as pouring the reaction mixture into water, extraction with an organic solvent followed by concentration of the extract. Compound (f) can, if required, clear, chromatography, recrystallization and the like.

(Second stage)

(1) the Case when R2represents C1-C5-alkyl group, optionally substituted by at least one halogen atom, C2-C5-alkenylphenol group, optionally substituted by at least one halogen atom, or alkylamino group, optionally substituted by at least one halogen atom.

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

Communication is usually carried out in a solvent.

The solvent used in the reaction includes, for example, ethers such as diethyl ether, tetrahydrofuran and so on is one, aromatic hydrocarbons, such as toluene, xylene and the like, and mixtures thereof.

ORGANOMETALLIC compounds used for the reaction include, for example, organic compounds of magnesium, such as methylmagnesium, ethylaniline, isopropylacrylamide, vinylmania, ethnicminority, dimethylamine and the like, organic compounds of lithium, such as motility and the like, organic zinc compounds such as diethylzinc and the like, and organic compound of copper, such as tricornered and the like.

The amount of ORGANOMETALLIC compound used for the reaction is usually 1 to 10 mol per mol of compound (f).

The reaction, if necessary, can be carried out in the presence of a salt of copper. Salts of copper used for the reaction include, for example, iodide copper(I)bromide copper(I) and the like. The amount of salt of copper used for the reaction is usually 0.05 to 1 mol per 1 mol of compound (f).

The reaction temperature is usually in the range from -20 to 100°C., and the reaction time is usually in the range from 1 to 24 hours.

After completion of the reaction, the compound (a) can be distinguished by carrying out the subsequent processing of the reaction mixture, such as pouring the reaction mixture into water, extraction with an organic solvent followed by concentration of the extract is. Compound (a) can, if required, clear, chromatography, recrystallization and the like.

(2) the Case when R2represents a hydrogen atom.

The compound (a) can be obtained by transformation of a compound (f) by a redox reaction.

The reduction is usually carried out in a solvent.

Solvents used for this reaction include, for example, ethers such as diethyl ether, tetrahydrofuran and the like, aromatic hydrocarbons such as toluene, xylene and the like, alcohols such as methanol, ethanol, isopropanol and the like, water and mixtures thereof.

Reducing agent used for the reaction includes, for example, borohydride sodium.

The amount of reducing agent used for the reaction, usually 0.25-2 mol per 1 mol of compound (f).

The reaction temperature is usually in the range 0-50°C, and the reaction time is usually in the range from instant to 24 hours.

After completion of the reaction, the compound (a) can be distinguished by carrying out the subsequent processing of the reaction mixture, such as pouring the reaction mixture into water, extraction with an organic solvent followed by concentration of the extract. Compound (a) can, if required, to clear chromatography, paracrystalline the Oia and the like.

(3) the Case when R2represents cyano.

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

The reaction is usually conducted in a solvent.

The solvents used for the reaction include, for example, ethers such as diethyl ether, tetrahydrofuran and the like, aromatic hydrocarbons such as toluene, xylene and the like, and mixtures thereof.

Cyanide compounds used for the reaction include, for example, tetrabutylammonium cyanide.

The amount of cyanide compounds used for the reaction is usually 1 to 10 mol per 1 mol of compound (f).

The reaction temperature is usually in the range from -20 to 100°C., and the reaction time is usually in the range from 1 to 24 hours.

After completion of the reaction, the compound (a) can be distinguished by carrying out the subsequent processing of the reaction mixture, such as pouring the reaction mixture into water, extraction with an organic solvent followed by concentration of the extract. Compound (a) can, if required, clear, chromatography, recrystallization and the like.

(Reference example obtaining 2)

The compound (d) can be obtained by the interaction of the compounds (b) with malononitrile.

where in the formula E1, R3and R4they shall have the same meanings, as explained above.

The reaction is usually carried out in a solvent and in the presence of a base.

The solvents used for the reaction include, for example, acid amides such as N,N-dimethylformamide and the like; ethers such as diethyl ether, tetrahydrofuran and the like, organic sulfur compounds such as dimethylsulfoxide, sulfolane and the like, halogenated hydrocarbons such as 1,2-dichloroethane, chlorobenzene and the like, aromatic hydrocarbons such as toluene, xylene and the like, and mixtures thereof.

Used for the reaction includes, for example, inorganic bases such as sodium hydride, sodium carbonate, potassium carbonate and the like, alkoxides of alkali metals, such as tert-piperonyl potassium and the like, amides of alkali metals, such as diisopropylamide lithium and the like, and organic bases, such as dimethylaminopyridine, 1,4-diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]-7-undecene and the like.

The amount of base used for the reaction is usually 1 to 10 mol per 1 mol of compound (b).

The number of malononitrile used for the reaction is usually 1 to 10 mol per 1 mol of compound (b).

The reaction temperature is usually in the range from -20 to 100°C., and the reaction time is usually in the range from 1 is about 24 hours.

After completion of the reaction, the compound (d) can be distinguished by carrying out the subsequent processing of the reaction mixture, such as pouring the reaction mixture into water, extraction with an organic solvent followed by concentration of the extract. Compound (d) can, if required, clear, chromatography, recrystallization and the like.

(Reference method for the preparation of 3)

The compound (d) can be obtained as follows.

where in the formula, R3and R4have the same meanings as described above.

(The first stage)

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

The reaction is usually conducted in a solvent. The solvents used for the reaction include, for example, acid amides such as N,N-dimethylformamide and the like; ethers such as diethyl ether, tetrahydrofuran and the like, halogenated hydrocarbons such as chloroform, 1,2-dichloroethane, chlorobenzene and the like, aromatic hydrocarbons such as toluene, xylene and the like, alcohols such as methanol, ethanol, isopropanol and the like, and mixtures thereof.

The reaction, if required, is carried out in the presence of a base. The base used for the reaction include, for example, tetrabutylammonium hydroxide and the like.

The number is on the base, used for the reaction is usually from 0.01 to 0.5 mol per 1 mol of compound (g).

The number of malononitrile used for the reaction is usually 1 to 10 mol per 1 mol of compound (g).

The reaction temperature is usually in the range from -20 to 100°C., and the reaction time is usually in the range from 1 to 24 hours.

The reaction, if necessary, can be performed along with removing from the reaction system, the water formed during the reaction.

After completion of the reaction, the compound (h) can be distinguished by carrying out the subsequent processing of the reaction mixture, such as pouring the reaction mixture into water, extraction with an organic solvent followed by concentration of the extract. Compound (h) can, if required, clear, chromatography, recrystallization and the like.

(Second stage)

The compound (d) can be obtained by transformation of a compound (h) by interacting with the regenerating agent.

The reduction is usually carried out in a solvent.

Solvents used for this reaction include, for example, alcohols such as methanol, ethanol, isopropyl alcohol, tert-butyl alcohol and the like, ethers such as diethyl ether, tetrahydrofuran and the like, halogenated hydrocarbons such as 1,2-dichloroethane, chlorobenzene and the like, aromatice the Kie hydrocarbons, such as toluene, xylene and the like, and mixtures thereof.

Reducing agent used for the reaction includes, for example, borohydride sodium, borohydride lithium, diisobutylaluminium and the like.

The amount of reducing agent used for the reaction depends on the type used for the reaction of the reducing agent, it is usually 0.25 to 5 mol per 1 mol of compound (h).

The reaction temperature is usually in the range from -20 to 100°C., and the reaction time is usually in the range from 1 to 24 hours.

After completion of the reaction, the compound (d) can be distinguished by carrying out the subsequent processing of the reaction mixture, such as pouring the reaction mixture into water, extraction with an organic solvent followed by concentration of the extract. Compound (d) can, if required, clear, chromatography, recrystallization and the like.

(Reference method 4)

The compound (C-1), in which R2represents a hydrogen atom in the compound (C)can be obtained as follows.

where in the formula E1, R1, R5X1X2and X3have the same meanings as described above.

(The first stage)

The compound (j-1) can be obtained by the interaction of the compound (k) with R1-CHO.

The reaction Prov is car Ried out in the presence or absence of a solvent. When the reaction is carried out in the presence of a solvent, the solvent used for the reaction include, for example, aromatic hydrocarbons such as toluene, benzene and the like, halogenated hydrocarbons such as chlorobenzene and the like, and mixtures thereof.

The reaction, if required, is carried out in the presence of a base. When the reaction is carried out in the presence of a base, the base used for the reaction include, for example, organic bases such as triethylamine, ethyldiethanolamine and the like, and the amount of base used for the reaction is usually 0.5 to 5 mol per 1 mol of compound (k).

The number R1CHO used for the reaction is usually 1 to 10 mol per 1 mol of compound (k).

The reaction temperature is usually in the range of 50-150°C., and the reaction time is usually in the range of 1-24 hours.

After completion of the reaction, the compound (j-1) can be distinguished by carrying out the subsequent processing of the reaction mixture, such as adding organic solvents, including acetone to the reaction mixture, if desired, and filtering the reaction mixture, and then concentrating the filtrate. A dedicated connection (j-1) can, if required, clear, chromatography, recrystallization and the like.

(Second stage)

The compound (C-1) the floor is given by halogenoalkanes connection (j-1), for example, the interaction of the compound (j-1) with a halogenation agent such as thionyl chloride, phosphorus oxychloride, and the like; or sulfonyloxy esterification, such as the interaction of the compound (j-1) with a sulfonic acid anhydride or sulphonylchloride, such as the anhydride triftormetilfullerenov acid, methanesulfonate, toluensulfonate and the like.

Among the compounds (C), (e), (k) and (j-1) a compound in which X1X2and X3represent CR6be synthesized according to the method described in Houben-Weyl, Methods der Organischen Chemi, Hetarene I, Teil. 1, p. 556-779.

Among the compounds (C), (e), (k) and (j-1) a compound in which X1represents a nitrogen atom and X2and X3represent nitrogen atoms, can be synthesized according to the method described in Houben-Weyl, Methods der Organischen Chemi, Hetarene III, Teil. 3, p. 399-710.

Among the compounds (C), (e), (k) and (j-1) a compound in which X2represents a nitrogen atom and X1and X3represent CR6be synthesized according to the method described in Houben-Weyl, Methods der Organischen Chemi, Hetarene III, Teil. 3, p. 1-192.

Among the compounds (C), (e), (k) and (j-1) a compound in which X1and X2represent nitrogen atoms and X3represents CR6be synthesized according to the method described in Houben-Weyl, Methods der Organischen Chemi, Hetaree III, Teil. 4, p. 305-389.

Among the compounds (C), (e), (k) and (j-1) a compound in which X1and X3represents a nitrogen atom and X2represents CR6be synthesized according to the method described in Houben-Weyl, Methods der Organischen Chemi, Hetarene III, Teil. 4, p. 479-586.

Among the compounds (C), (e), (k) and (j-1) a compound in which X1X2and X3represent nitrogen atoms, can be synthesized according to the method described in Houben-Weyl, Methods der Organischen Chemi, Hetarene I, Teil. 4, p. 664-777.

Pests of, in the struggle with which the compounds of the present invention have activity may include, for example, arthropod pests, such as insects and mites-pests and the like, and nematode pests. Specific examples of them are listed below:

Hemiptera (Heteroptera insects):

Delphacidae, such as Laodelphax striatellus, Nilaparvata lugens, Sogatella furcifera, and the like,

Deltocephalidae, such as Nephotettix cincticeps, Nephotettix virescens and the like,

Aphididae, such as Aphis gossypii, Myzus persicae, and the like,

Pentatomidae, such as Nezara antennata, Riptortus clavetus, Eysarcoris lewisi, Eysarcoris parvus, Plautia stali, Halyomorpha mista and the like,

Aleyrodidae, such as Trialeurodes vaporariorum, Bemisia argentifolii, and the like,

Coccidae such as Aonidiella aurantii, Comstockaspis perniciosa, Unaspis citri, Ceroplastes rubens, Icerya purchasi and the like,

Tingidae,

Psyllidae, and the like;

Lepidoptera (Lepidoptera insects):

Pyralidae, t is such as Chilo suppressalis, Cnaphalocrocis medinalis, Notarcha derogata, Plodia interpunctella and the like,

Noctuidae such as Spodoptera litura, Pseudaletia separata, Thoricoplusia spp., Heliothis spp., Helicoverpa spp. and the like,

Pieridae such as Pieris rapae and the like,

Tortricidae such as Adoxophyes spp., Grapholita molesta, Cydia pomonella, and the like,

Carposinidae such as Carposina niponensis and the like,

Lyonetiidae, such as Lyonetia spp. and the like,

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

Yponomeutidae such as Plutella xylostella, and the like,

Gelechiidae such as Pectinophora gossypiella and the like,

Arctiidae such as Hyphantria cunea and the like,

Tineidae such as Tinea translucens, Tineola bisselliella, and the like;

Diptera (two-winged insects):

Calicidae, such as Culex pipiens pallens, Culex tritaeniorhynchus, Culex quinquefasciatus, and the like,

Aedes spp., such as Aedes aegypti, Aedes albopictus, and the like,

Anopheles spp., such as Anopheles sinensis and the like,

Chironomidae,

Muscidae such as Musca domestica, Muscina stabulans, and the like,

Calliphoridae,

Sarcophagidae,

Fanniidae,

Anthomyiidae such as Delia platura, Delia antiqua, and the like,

Tephritidae,

Drosophilidae,

Psychodidae,

Tabanidae,

Simuliidae,

Stomoxyidae,

Agromyzidae, and the like;

Coleoptera (beetles):

Diabrotica spp., such as Diabrotica virgifera virgifera, Diabrotica undecimpunctata howardi, and the like,

Scarabaeidae such as Anomala cuprea, Anomala rufocuprea, and the like,

Curculionidae, such as Sitophilus zeamais, Lissorhoptrus oryzophilus, Callosobruchuys chienensis and so on is one,

Tenebrionidae, such as Tenebrio molitor, Tribolium castaneum, and the like,

Chrysomelidae, such as Oulema oryzae, Aulacophora femoralis, Phyllotreta striolata, Leptinotarsa decemlineata, and the like,

Anobiidae,

Epilachna spp., such as Epilachna vigintioctopunctata and the like,

Lyctidae,

Bostrychidae,

Cerambycidae,

Paederus fuscipes;

Blattodea (such relic species of insects):

Blattella germanica, Periplaneta fuliginosa, Periplaneta americana, Periplaneta brunnea, Blatta orientalis, and the like;

Thysanoptera (Puzanova insects):

Thripspalmi, Thrips tabaci, Frankliniella occidentalis, Frankliniella intonsa, and the like;

Hymenoptera (Hymenoptera insects):

Formicidae, Vespidae, bethylid wasp, Tenthredinidae, such as Athalia japonica, and the like;

Orthoptera insects):

Gryllotalpidae, Acrididae, and the like;

Aphaniptera:

Ctenocephalides felis, Ctenocephalides canis, Pulex irritans, Xenopsylla cheopis, and the like;

Anoplura (lice):

Pediculus humanus corporis, Phthirus pubis, Haematopinus eurysternus, Dalmalinia ovis and the like;

Isoptera (termites):

Reticulitermes speratus, Coptotermes formosanus, and the like;

Acarina (mites):

Tetranychidae such as Tetranychus urtlcae, Tetranychus kanzawai, Panonychus citri, Panonychus ulmi, Oligonychus spp. and the like,

Eriophyidae such as Aculops pelekassi, Aculus schlechtendali, and the like,

Tarsonemidae such as Polyphagotarsonemus latus and the like,

Tenuipalpidae,

Tuckerellidae,

Ixodidae such as Haemaphysalis longicornis, Haemaphysalis flava, Dermacentor taiwanicus, Ixodes ovatus, Ixodes persulcatus, Boophilus microplus, and the like,

Acaridae such as Tyrophagus putrescentiae, and the like,

Epidermoptidae, such as Dermatophagoides fainae, Dermatophagoides ptrenyssnus and the like,

Cheyletidae such Cheyletus eruditus, Cheyletus malaccensis, and Cheyletus moorei, and the like,

Dermanyssidae;

Araneae (spiders):

Chiracanthium japonicum, Latrodectus hasseltii, and the like;

Chilopoda (Gubanova insects):

Thereuonema hilgendorfi, Scolopendra subspinipes, and the like;

Diplopoda (duparinova):

Oxidus gracilis, Nedyopus tambanus and the like;

Isopoda:

Armadillidium vulgare and the like;

Gastropoda (gastropods):

C limax vaginal marginatus, C limax vaginal flavus and the like;

Nematoda (nematodes):

Pratylenchus coffeae, Pratylenchus fallax, Heterodera glycines, Globodera rostochiensis, Meloidogyne hapla, Meloidogyne incognita, and the like.

The pesticide composition of the present invention contains an effective amount of the compounds of the present invention and an inert carrier. Usually it is a preparation obtained by mixing the compounds of the present invention and a carrier, such as a solid carrier, liquid carrier and/or gaseous media, and, if necessary, adding a surfactant and other additives to the drug. The drug includes, for example, emulsifiable concentrate, oil solution, the drug is in the form of a shampoo, loose powder, dust, wettable powder, granules, the product in paste form, microcapsules, foam, aerosol, drug with gaseous carbon dioxide, tablets and the drug in the resin. These drugs can be transformed for use in poisoned bait, FR is moskitoo spiral, electric mosquito Mat, agent for fumigation, fumigant or floor.

In the pesticide composition of the present invention, the compound of the present invention is usually contained in an amount of 0.1-95 wt.%.

Solid carriers for drug include, for example, fine powder or granules of clays (e.g. kaolin, diatomaceous earth, bentonite, Fubasami clay, acid clay, etc), synthetic hydrated silicon oxide, talc, ceramics, other inorganic materials (e.g., sericite, quartz, sulfur, activated carbon, calcium carbonate, hydrated silica) or chemical fertilizers (e.g. ammonium sulfate, ammonium phosphate, ammonium nitrate, ammonium chloride, urea).

Liquid carriers for drug include, for example, aromatic or aliphatic hydrocarbons (e.g. xylene, toluene, alkylnaphthalene, phenylxylylethane, kerosene, light oil, hexane, cyclohexane), halogenated hydrocarbons (e.g. chlorobenzene, dichloromethane, dichloroethane, dichloromethane), alcohols (e.g. methanol, ethanol, isopropyl alcohol, butanol, hexanol, ethylene glycol), ethers (e.g. diethyl ether, dimethyl ether of ethylene glycol, onomatology ether of diethylene glycol, monotropy ether of diethylene glycol, onomatology ether of propylene glycol, tetrahydrofuran, dioxane), complex EPE is s (e.g., ethyl acetate, butyl acetate), ketones (e.g. acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone), NITRILES (e.g. acetonitrile, isobutyronitrile), sulfoxidov (e.g., dimethylsulfoxide), acid amides (e.g. N,N-dimethylformamide, N,N-dimethylacetamide), vegetable oils (e.g. soybean oil, cotton seed oil), vegetable oils (for example, orange oil, hyssop, lemon oil) and water.

Gaseous carriers for drug include, for example, gaseous butane, chlorofluorocarbons, liquefied petroleum gas (LPG), dimethyl ether, carbon dioxide, and the like.

Surfactants include, for example, alkylsulfate salts, alkylsulfonic acids, salts alkylarylsulfonate acids, alkylsilane ethers and their polyoxyethylenated, ethers of glycols, esters of polyhydric alcohols and derivatives of alcohols of a number of sugars.

Other additives to the drug include binders, dispersing agents, stabilizers and the like, in particular, for example, casein, gelatin, polysaccharides (e.g. starch, Arabic gum, cellulose derivatives, alginic acid), lignin derivatives, bentonite, sugars, synthetic water-soluble polymers (e.g. polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic Ki the lot) 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 basis for the drug in the resin include, for example, a copolymer based on polyvinyl chloride, polyurethane and the like. To these basics, if you want, you can add a plasticizer such as phthalate (for example, dimethylphthalate, dioctylphthalate), adipate and stearates. The drug in the resin can be obtained by mixing such compounds in the basis using a known kneader machine, and then the molding molding molding, extrusion molding, press molding and the like, and, furthermore, if necessary, by way of molding, cutting and the like, the drug in the resin can be converted into such a form of the drug in the resin, as a panel, film, tape, mesh, cord and the like. These drugs in the resin can be converted, for example, in the collar or clamp for animal ear tags for animals, the drug is in the form of a sheet, cord stool, props for gardening.

The basis for the use of poison baits include, for example, flour of cereals, vegetable oil, sugar and crystalline cellulose, and, in addition, if necessary, to the base can be added antioxidants, such as dibutylaminoethanol and notigi requiredby acid, preservatives such as dehydroacetic acid, agents for preventing eating the bait by children and Pets, such as powder of pepper burning, and luring insects aromatic additives such as an additive cheese smell, additive onion smell and peanut butter.

Pests can be controlled by applying effective amounts of the compounds of the present invention directly on the pests and/or habitats of pests (e.g., plants, animals, soil). The drug pesticide composition of the present invention is usually used as a method of pest control in accordance with the present invention.

When the pesticidal composition of the present invention is used for pest control in agriculture and forestry, the damage amount is typically about 1-10000 g/ha, preferably 10-1000 g/ha active ingredient. Preparations in the form of emulsifiable concentrates, wettable powders, flowable formulations and microcapsules is usually applied after dilution with water to have a concentration of active ingredient 1-10000 ppm, whereas dusty and pellets are usually applied as such. These drugs can be sprayed directly on the plant, which protects against pests. Pests living in the soil can be controlled by tillage this is mi drugs, and drugs can also be used for the treatment beds before planting or processing of planting holes or the bottom of the plants when planting. In addition, the drug in the form of sheets pesticide composition of the present invention can be applied in such a way as wrapping them around the plants, stretch near the plants and covering the soil surface at the lower parts of plants.

When the pesticidal composition of the present invention is used during the epidemic period, the applicable amount is usually 0.001 to 10 mg/m3as the active ingredient in the case of applications for open space and 0.001-100 mg/m2as the active ingredient in the case of coating on the surface of plants. Preparations in the form of emulsifiable concentrates, wettable powders, flowable formulations and microcapsules is usually applied after dilution with water to have a concentration of active ingredient is from 0.01 to 10000 ppm, whereas oil solutions, aerosols, agents for fumigation and the use of poison baits used as such.

When the pesticidal composition of the present invention is used for combating parasites, living on the outside of livestock such as cow, horse, pig, sheep, goat and chicken, and a small animal, such as dog, cat, rat and mouse, the pesticide composition may amosite specified animal method, known in veterinary medicine. In particular, for the system fight the pesticide composition is administered by means of, for example, tablets, mix with food, suppository or injection (e.g., intramuscular, subcutaneous, intravenous, intraperitoneal) and for non-systemic struggle it is used in such a way that the spray oil solution or aqueous liquid preparation, processing, brandy or processing spots, wash the specified animal drug in the form of a shampoo, the attachment of the drug in the resin to the specified animal in the form of a collar or collar or ear tag, and the like. When the compound of the present invention is administered to an animal, it usually is in the range of 0.1-1000 mg/kg animal body weight.

The pesticide composition of the present invention can also be used in mixture or in combination with other insecticides, nematicides, acaricides, fungicides, herbicides, plant growth regulators, synergists, fertilizers, builders, fodder for animals and the like.

Active ingredients such other insecticide and acaricide include, for example, PYRETHROID compounds such as allethrin, tetramethrin, prallethrin, phenothrin, resmethrin, cyphenothrin, permethrin, cypermethrin, alpha-cypermethrin, Zeta-cypermethrin, deltamethrin, tralomethrin, cyfluthrin, beta-C is fluten, cigalotrin, lambda cigalotrin, flumethrin, imiprothrin, etofenprox, fenvalerate, esfenvalerate, fenpropathrin, selflove, bifenthrin, transfluthrin, flucythrinate, Tau-fluvalinate, acrinathrin and tefluthrin; organophosphorus compounds such as dichlorvos, fenitrothion, cyanophos, 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, bentaleb, oxamyl, aldicarb and methiocarb; derivative benzoylferrocene, such as lufenuron, chlorfluazuron, hexaflumuron, diflubenzuron, triflumuron, diflubenzuron, flufenoxuron, fluazuron, novaluron and treasure; such juvenile hormone agents such as pyriproxyfen, methoprene, hydroprene and fenoxycarb; neonicotinoid compounds such as acetamiprid, nitenpyram, thiacloprid, thiamethoxam and dinotefuran; derivatives of N-phenylhydrazine, such as acetool and ethiprole; derivatives benzoylhydrazone, such as tebufenozide, chromafenozide, methoxyfenozide and halogenated; diafenthiuron; piperazin; flonicamid; triazamate; buprofezin; spinosad; emamectin benzoate; chlorfenapyr; indoxacarb Mr; pyridalyl; cyromazine; fenpyroximate; teba is inpired; elfenberg; pyridaben; pyrimidifen; flociprin; etoxazole; finishin; achiezer; hexythiazox; clofentezine; fenbutatin oxide; dicofol, propargite; abamectin; milbemectin; amitraz; cartap; bensultap; thiocyclam; endosulfan; spirodiclofen; spiromesifen and azadirachtin.

Active ingredients such other fungicide include, for example, strobilurin compounds such as AZOXYSTROBIN; organophosphorus compounds such as tolclofos-methyl; derivative azole, such as triflumizole, perforated and difenoconazole; phtalic; flutolanil; validamycin; provenzal; declomycin; pencycuron; dazomet, kasugamycin; IBP; pyroquilon; oxolinic acid, tricyclazole; parison; mepronil; EDDP; isoprothiolane; carprofen; declocked; formerip; fludyoksonil; procymidon and dietphenterm.

EXAMPLES

The present invention is described in more detail included in the description of examples of the preparation, sample preparations, examples, tests and the like, which should not be construed as limiting the invention.

The present invention is illustrated by the following examples of the preparation of compounds of the present invention.

Example obtain 1

0,76 g of the Hydrochloride of 1-(chloromethyl)-1H-pyrazole and 0.81 g of (3,3,3-cryptochromes)malononitrile dissolved in 10 ml of N,N-dimethylformamide. To the solution while cooling l the house added under stirring to 1.38 g of potassium carbonate, followed by stirring the mixture at room temperature for 5 hours. To the reaction mixture, water is added and the mixture is then extracted with a simple methyl tert-butyl ether (hereinafter referred to MTBE). The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is recrystallized from a mixture of hexane-ethyl acetate, thus obtaining 0.36g (1H-pyrazole-1-ylmethyl)(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (1) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,21-of 2.27 (2H, m), 2,47 at 2.59 (2H, m), was 4.76 (2H, s), 6.42 per (1H, t), 7,63-to 7.64 (2H, m).

Example of getting 2

of 0.77 g of the Hydrochloride of 3-isopropyl-1-(chloromethyl)-1H-pyrazole and 0.64 g of (3,3,3-cryptochromes)malononitrile dissolved in 8 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.54 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel and then recrystallized from a mixture of hexane-ethyl acetate, thus obtaining 0,42 g [(3-isopropyl-1H-pyrazole-1-yl)methyl]-(3,3,3-crypto is propyl)malononitrile (hereinafter referred to compound (2) of the present invention), the formula which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,24 (6N, e), 2,20-of 2.24 (2H, m), 2,47-of 2.58 (2H, m), 2,93-3,00, (1H, m), 4,34 (2H, s), of 6.20 (1H, d), to 7.50 (1H, d).

Example of getting 3

of 1.16 g of the Hydrochloride of 3-tert-butyl-1-(chloromethyl)-1H-pyrazole and 0.98 g of (3,3,3-cryptochromes)malononitrile dissolved in 17 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.54 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,63 g [(3-tert-butyl-1H-pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (hereinafter referred to compound (3) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 1.28 (in N, C), 2,19-of 2.24 (2H, m), 2,48-to 2.57 (2H, m), with 4.64 (2H, s), 6,23 (1H, d), 7,49 (1H, d).

Example 4

1.24 g of the Hydrochloride of 3-tert-butyl-1-(chloromethyl)-1H-pyrazole and 0.63 g of allylmalonate dissolved in 18 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.63 g of potassium carbonate followed the m by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,38 g of allyl-[(3-tert-butyl-1H-pyrazole-1-yl)methyl]malononitrile (hereinafter referred to compound (4) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,30 (N, C)2,69 (2H, DD), 4,58 (2H, s), the 5.45 the 5.51 (2H, m), 5,88 of 5.99 (1H, m), 6,21 (1H, d), of 7.48 (1H, d).

Example of getting 5

of 0.58 g of the Hydrochloride of 2-(chloromethyl)-6,6-dimethyl-2,4,5,6-tetrahydrocyclopent[c]pyrazole and 0.43 g of (3,3,3-cryptochromes)malononitrile dissolved in 8 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 0.73 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0.27 g [(6,6-dimethyl-5,6-dihydrocyclopenta[c]pyrazole-2(4H)-yl)ethyl]-(3,3,3-cryptochromes)malononitrile (hereinafter referred to compound (5) is altoadige of the invention), the formula which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,24 (6N, (C), 2,15-of 2.23 (4H, m), 2,42-to 2.65 (4H, m), 5,97 (2H, s), to 7.15 (1H, s).

An example of obtaining 6

1.44 g of 1-(Chloromethyl)-3-(trifluoromethyl)-1H-pyrazole and of 1.30 g of (3,3,3-cryptochromes)malononitrile dissolved in 16 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 2.21 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to recrystallization from a mixture of hexane-ethyl acetate, thus obtaining 0.87 g {[3-(trifluoromethyl)-1H-pyrazole-1-yl]methyl}-(3,3,3-cryptochromes)malononitrile (hereinafter referred to compound (6) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,25-to 2.29 (2H, m), 2,50-2,61 (2H, m), and 4.75 (2H, s)6,70 (1H, s), 7,72 (1H, s).

Example of getting 7

of 1.33 g of 1-(Chloromethyl)-3-(trifluoromethyl)-1H-pyrazole and 0,76 g allylmalonate dissolved in 21 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.99 g of potassium carbonate, followed by stirring the mixture at ControlTemplate during the night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is recrystallized from a mixture of hexane-ethyl acetate, thus obtaining 0,57 g allyl-{[3-(trifluoromethyl)-1H-pyrazole-1-yl]methyl}malononitrile (hereinafter referred to compound (7) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,74 (2H, d), 4,69 (2H, s), 5,49 is 5.54 (2H, m), by 5.87 is 5.98 (1H, m), to 6.67 (1H, s), 7,71 (1H, s).

Example obtain 8

of 1.57 g of the Hydrochloride of 1-chloromethyl-3-formylpyrazole and 1.52 g of (3,3,3-cryptochromes)malononitrile dissolved in 30 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 2.76 g of potassium carbonate, followed by stirring the mixture at room temperature for 5 hours. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0.05 g of [(3-formyl-1H-pyrazole-1-yl]methyl]-(3,3,3-cryptochromes)malononitrile (hereinafter referred to compound (8) of the present invention), the formula of which is shown below.

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1H-NMR (CDCl3, TMS, δ (ppm)): 2,28-of 2.34 (2H, m), 2,52-2,63 (2H, m), of 4.77 (2H, s), 6,93 (1H, s), of 7.70 (1H, s), 9,99 (1H, s).

Example of getting 9

to 1.00 g of 1-(Chloromethyl)-3-cyano-1H-pyrazole, and 1.15 g of (3,3,3-cryptochromes)malononitrile dissolved in 21 ml of N,N-dimethylformamide. To the solution while cooling with ice added under stirring to 1.96 g of potassium carbonate, followed by stirring the mixture at room temperature for 5 hours. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1,11 g [(3-cyano-1H-pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (hereinafter referred to compound (9) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,23-of 2.27 (2H, m), 2,49-2,60 (2H, m), and 4.75 (2H, s), 7,60 (1H, s), 7,66 (1H, s).

Example 10

a 2.01 g of the Hydrochloride of 1-(chloromethyl)-3-phenyl-1H-pyrazole and 1.42 g of (3,3,3-cryptochromes)malononitrile dissolved in 27 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing 2,43 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To R the promotional mix water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0.66 g [(3-phenyl-1H-pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (hereinafter referred to compound (10) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,33-is 2.37 (2H, m), 2,53-2,62 (2H, m), to 4.73 (2H, s)6,70 (1H, d), 7,33-7,44 (3H, m), of 7.64 (1H, d), 7,87-7,80 (2H, m).

Example of getting 11

to 1.38 g of the Hydrochloride of 4-bromo-3-isopropyl-1-(chloromethyl)-1H-pyrazole and 0.81 g of (3,3,3-cryptochromes)malononitrile dissolved in 15 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.38 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,91 g [(4-bromo-3-isopropyl-1H-pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (also called connection (11) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,25 (6N, e), 2,20-to 2.29 (2H, m), of 2.51-of 2.58 (2H, m), 3.00 and-a 3.06 (1H, m), 4,60 (2H, s), 7,56 (1H, s).

Example 12

1.85 g of the Hydrochloride of 4-bromo-3-tert-butyl-1-(chloromethyl)-1H-pyrazole and 1.18 g of (3,3,3-cryptochromes)malononitrile dissolved in 21 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing 2,02 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1,91 g [(4-bromo-3-tert-butyl-1H-pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (hereinafter referred to compound (12) of the present invention), the formula of which is shown below.

1H-NMR (Dl3, TMS, δ (ppm)): 1,38 (N, C), 2,20-of 2.23 (2H, m), 2,49-2,61 (2H, m), of 4.57 (2H, s), EUR 7.57 (1H, s).

Example of getting 13

0,98 g of the Hydrochloride of 4-chloro-3-tert-butyl-(1-chloromethyl)-1H-pyrazole and 0.65 g of (3,3,3-cryptochromes)malononitrile dissolved in 12 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.11 g of potassium carbonate, followed by stirring the mixture at room temperature is f during the night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0.40 g of [(4-chloro-3-tert-butyl-1H-pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (hereinafter referred to compound (13) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,36 (N, C), 2,20-of 2.24 (2H, m), 2,49-2,61 (2H, m), 4,56 (2H, s), 7,54 (1H, s).

Example of getting 14

1.84 g of the Hydrochloride of 4-bromo-3-tert-butyl-1-(chloromethyl)-1H-pyrazole and 0.77 g of allylmalonate dissolved in 21 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing 2,02 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0.84 g allyl-[(4-bromo-3-tert-butyl-1H-pyrazole-1-yl)methyl]malononitrile (hereinafter referred to compound (14) of the present invention), the formula of which is shown the lower is.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,40 (N, C), a 2.71 (2H, d), 4,51 (2H, s), 5,43-5,52 (2H, m), by 5.87 is 5.98 (1H, m), 7,56 (1H, s).

Example get 15

1,67 g of 4-Bromo-1-(chloromethyl)-3-trifluoromethyl-1H-pyrazole and 1.03 g of (3,3,3-cryptochromes)malononitrile dissolved in 18 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.74 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0.97 g allyl-[(4-bromo-3-trifluoromethyl-1H-pyrazole-1-yl)methyl]-(3,3,3-trifluoromethyl)malononitrile (hereinafter referred to compound (15) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,25-of 2.30 (2H, m), 2,49-2,62 (2H, m), 4,70 (2H, s), to 7.77 (1H, s).

Example 16

1,67 g of 4-Bromo-1-(chloromethyl)-3-(trifluoromethyl)-1H-pyrazole and 0.67 g of allylmalonate dissolved in 18 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.74 g of potassium carbonate, followed by stirring the mixture at room temperature for whom the night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,90 g allyl-{[4-bromo-(3-trifluoromethyl)-1H-pyrazole-1-yl]methyl}malononitrile (hereinafter referred to compound (16) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,75 (2H, d), 4,63 (2H, s), 5,50-of 5.55 (2H, m), 5,86-5,97 (1H, m), 7,76 (1H, s).

Example of getting 17

0,93 g of the Hydrochloride of 1-(chloromethyl)for 3,5-dimethyl-1H-pyrazole and 0.81 g of (3,3,3-cryptochromes)malononitrile dissolved in 15 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.38 g of potassium carbonate, followed by stirring the mixture at room temperature for 4 hours. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0.45 g of compound (hereinafter referred to compound (17) of the present invention), the formula of which is shown below.

1Mr. YAM is (CDCl 3, TMS, δ (ppm)): of 2.23 (3H, s), is 2.37 (3H, s), 2,41-2,61 (4H, m)to 4.52 (2H, s), 5,91 (1H, s).

Example of getting 18

of 1.46 g of the Hydrochloride of 1-(chloromethyl)-4-methyl-1H-pyrazole and 1.42 g of (3,3,3-cryptochromes)malononitrile dissolved in 30 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 2.40 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,83 g of compound (hereinafter referred to compound (18) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,11 (3H, s), 2,20-of 2.24 (2H, m), 2,46-of 2.58 (2H, m), with 4.64 (2H, s), 7,38 (1H, s), 7,42 (N, C).

Example of getting 19

1.44 g of the Hydrochloride of 4-chloro-1-(chloromethyl)-1H-pyrazole and 1.56 g of (3,3,3-cryptochromes)malononitrile dissolved in 30 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 2.76 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with the ode, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1.73 g of [(4-chloro-1H-pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (hereinafter referred to compound (19) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,17-2,31 (2H, m), 2,46-2,60 (2H, m), with 4.64 (2H, s), EUR 7.57 (1H, s), 7,63 (1H, s).

Example of getting 20

1,43 g of the Hydrochloride of 4-chloro-1-(chloromethyl)-1H-pyrazole and 1.01 g of allylmalonate dissolved in 30 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 2.76 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1.22 g allyl-[(4-chloro-1H-pyrazole-1-yl)methyl]malononitrile (also called connection (20) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,72 (2H, d), 4,58 (2H, s), 5,46-5,52 (2H, m), by 5.87 is 5.98 (1H, m), EUR 7.57 (1H, s), 7,63 (1H, s).

the example of obtaining 21

of 3.27 g of the Hydrochloride of 4-bromo-1-(chloromethyl)-1H-pyrazole and to 2.29 g of (3,3,3-cryptochromes)malononitrile dissolved in 28 ml of N,N-dimethylformamide. To the solution while cooling with ice added under stirring to 3.89 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 3.28 g of [(4-bromo-1H-pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (also called connection (21) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,17-of 2.27 (2H, m), 4,48-2,60 (2H, m), of 4.66 (2H, s), 7,60 (1H, s), the 7.65 (1H, s).

Example of getting 22

of 0.60 g of 1-(Chloromethyl)-4-(trifluoromethyl)-1H-pyrazole and 0.54 g of (3,3,3-cryptochromes)malononitrile dissolved in 10 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 0.99 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel and then recrystallized from a mixture of hexane-chloroform, while receiving 0,19 g {[4-(trifluoromethyl)-1H-pyrazole-1-yl]methyl}-(3,3,3-cryptochromes)malononitrile (also called connection (22) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,28 of-2.32 (2H, m), 2,53-to 2.57 (2H, m), 4,71 (2H, s), a 7.85 (1H, s), to 7.93 (1H, s).

An example of retrieving 23

to 0.80 g of 1-(Chloromethyl)-4-methoxycarbonyl-1H-pyrazole and 0.75 g of (3,3,3-cryptochromes)malononitrile dissolved in 15 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.27 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel and then recrystallized from a mixture of hexane-chloroform, while receiving 0,48 g [{4-(methoxycarbonyl)-1H-pyrazole-1-yl}methyl]-(3,3,3-cryptochromes)malononitrile (also called connection (23) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, who (ppm)): 2,27 of-2.32 (2H, m), 2,47-2,62 (2H, m), 3,86 (3H, s), 4,71 (2H, s), 8,03 (1H, s)to 8.12 (1H, s).

Example of getting 24

0,79 g of 1-(Chloromethyl)-4-methoxycarbonyl-1H-pyrazole and 0.49 g of allylmalonate dissolved in 15 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.26 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel and then recrystallized from a mixture of hexane-chloroform, thus obtaining 0.50 g allyl-[{4-(methoxycarbonyl)-1H-pyrazole-1-yl}methyl]malononitrile (also called connection (24) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): was 2.76 (2H, d), of 3.85 (3H, s), with 4.64 (2H, s), 5,47 is 5.54 (2H, m), 5,85 of 5.99 (1H, m), 8,02 (1H, s), 8,11 (1H, s).

Example get 25

1.13 g of 1-(Chloromethyl)-3-(trifluoromethyl)-4-etoxycarbonyl-1H-pyrazole and 0.71 g of (3,3,3-cryptochromes)malononitrile dissolved in 13 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.22 g of potassium carbonate, followed by stirring the mixture at room temperature during the night is. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,30 g {[4-etoxycarbonyl-3-(trifluoromethyl)pyrazole-1H-yl]methyl}-(3,3,3-cryptochromes)malononitrile (also called connection (25) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.37 (3H, t), 2,30-of 2.34 (2H, m), 2,52-2,63 (2H, m), 4,35 (2H, square), to 4.73 (2H, s), 8,24 (1H, s).

Example of getting 26

to 1.25 g of 1-(Chloromethyl)-3-(trifluoromethyl)-4-etoxycarbonyl-1H-pyrazole and 0.52 g of allylmalonate dissolved in 15 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.35 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel and then recrystallized from hexane, to thereby obtain 0.14 g of the allyl-{[4-etoxycarbonyl-3-(trifluoromethyl)pyrazole-1H-yl]methyl}malononitrile, " what about the next connection (26) of the present invention), the formula which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.36 (3H, t), 2,80 (2H, d), 4,30 (2H, square), and 4.68 (2H, s), 5,46-to 5.56 (2H, m), 5,88 is 5.98 (1H, m), 8,24 (1H, s).

Example of getting 27

of 0.77 g of the Hydrochloride of 1-(chloromethyl)-1H-1,2,4-triazole and 0.81 g of (3,3,3-cryptochromes)malononitrile dissolved in 15 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.38 g of potassium carbonate, followed by stirring the mixture at room temperature for 7 hours. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is recrystallized, while receiving 0,42 g [(1H-1,2,4-triazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (hereinafter referred to compound (27) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,31-is 2.37 (2H, m), 2,52-2,63 (2H, m), of 4.77 (2H, s), of 8.09 (1H, s), with 8.33 (1H, s).

Example of getting 28

0,78 g of the Hydrochloride of 3-isopropyl-1-(chloromethyl)-1H-1,2,4-triazole and 0.65 g of (3,3,3-cryptochromes)malononitrile dissolved in 12 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.10 g of potassium carbonate, followed by stirring the mixture at on the th temperature during the night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is recrystallized from a mixture of hexane-MTBE, while receiving 0.31 g [(3-isopropyl-1H-1,2,4-triazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (also called connection (28) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,32 (6N, e), 2,31 to 2.35 (2H, m), a 2.45-2.63 in (2H, m), 3,06-3,13 (1H, m), and 4.68 (2H, s), 8,19 (1H, s).

An example of obtaining 29

of 1.61 g of the Hydrochloride of 3-tert-butyl-1-(chloromethyl)-1H-1,2,4-triazole and 1.24 g of (3,3,3-cryptochromes)malononitrile dissolved in 22 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 2.13 g of potassium carbonate, followed by stirring the mixture at room temperature for 4 hours. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is recrystallized from a mixture of hexane-MTBE, while receiving 0,77 g [(3-tert-butyl-1H-1,2,4-triazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (29) of the present invention), the formula of which is shown on below.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,37 (N, C), 2,31-of 2.34 (2H, m), of 2.51 2.63 in (2H, m), of 4.67 (2H, s), 8,18 (1H, s).

Example 30

0,98 g of the Hydrochloride of 3-(1,1-dimethylpropyl)-1-(chloromethyl)-1H-1,2,4-triazole and 0.65 g of (3,3,3-cryptochromes)malononitrile dissolved in 12 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.11 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is recrystallized from a mixture of hexane-MTBE, while receiving 0,29 g {[3-(1,1-dimethylpropyl)-1H-1,2,4-triazole-1-yl]methyl}-(3,3,3-cryptochromes)malononitrile (denoted hereinafter by a connection (30) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 0,72 (3H, t), 1,33 (6N, (C), was 1.69 (2H, HF), 2,31 to 2.35 (2H, m), of 2.51 2.63 in (2H, m), and 4.68 (2H, s), 8,19 (1H, s).

An example of retrieving 31

1.28 g of the Hydrochloride of 1-(chloromethyl)-3-tert-butyl-1H-1,2,4-triazole and 0.77 g of allylmalonate dissolved in 21 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 1.01 g of potassium carbonate, followed by stirring a mixture of PR is room temperature for 4 hours. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is recrystallized from a mixture of hexane-MTBE, while receiving 0.16 g allyl-[(3-tert-butyl-1H-1,2,4-triazole-1-yl)methyl]malononitrile (also called connection (31) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,38 (N, C), and 2.79 (2H, d), br4.61 (2H, s), 5,50 is 5.54 (2H, m), of 5.89-6,00 (1H, m), 8,16 (1H, s).

Example of getting 32

2,03 g of the Hydrochloride of 5-bromo-3-tert-butyl-1-(chloromethyl)-1H-1,2,4-triazole and of 1.30 g of (3,3,3-cryptochromes)malononitrile dissolved in 24 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 2.21 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,76 g [(5-bromo-3-tert-butyl-1H-1,2,4-triazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (also called connection (32) of the present invention), the formula for which the CSO is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,34 (N, C), 2,40 at 2.45 (2H, m), of 2.51-of 2.64 (2H, m), to 4.62 (2H, s).

An example of obtaining 33

1.56 g of 1-(Chloromethyl)-3-(trifluoromethyl)-1H-1,2,4-triazole and 1.38 g of (3,3,3-cryptochromes)malononitrile dissolved in 25 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 2.35 g of potassium carbonate, followed by stirring the mixture at room temperature for 4 hours. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is recrystallized from a mixture of hexane-MTBE, while receiving 0.15 g {[3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl]methyl}-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (33) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,34-of 2.38 (2H, m), of 2.51-to 2.65 (2H, m), 4,82 (2H, s), to 8.45 (1H, s).

An example of retrieving 34

of 1.74 g of 1-(Chloromethyl)-3-(pentafluoroethyl)-1H-1,2,4-triazole and 1.20 g of (3,3,3-cryptochromes)malononitrile dissolved in 21 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing 2,04 g of potassium carbonate, followed by stirring the mixture at room temperature for 4 hours. To react the Onna mixture is added water and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is recrystallized from a mixture of hexane-MTBE, while receiving 0.25 g {[3-(pentafluoroethyl)-1H-1,2,4-triazole-1-yl]methyl}-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (34) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,32-of 2.36 (2H, m), 2,52-of 2.64 (2H, m), 4,84 (2H, s), of 8.47 (1H, s).

Example of getting 35

2.24 g of 1-(Chloromethyl)-3-(pentafluoroethyl)-1H-1,2,4-triazole and 1,02 g allylmalonate dissolved in 28 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 2.76 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, and then subjected to preparative high performance liquid chromatography, thus obtaining 0,54 g allyl-{[3-(pentafluoroethyl)-1H-1,2,4-triazole-1-yl]methyl}malononitrile (denoted hereinafter compound (35) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,81 (2H, d), was 4.76 (2H, s), of 5.53-5,59 (2H, m), 5,88-5,97 (1H, m), to 8.45 (1H, s).

Example of getting 36

a 2.01 g of 1-(Chloromethyl)-3-(pentafluoroethyl)-1H-pyrazole and 1.39 g (3,3,3-cryptochromes)malononitrile dissolved in 25 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 2.38 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1,31 g {[3-(pentafluoroethyl)-1H-pyrazole-1-yl]methyl}-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (36) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,23-of 2.27 (2H, m), 2.49 USD at 2.59 (2H, m), of 4.77 (2H, s), 6,72 (1H, d), of 7.75 (1H, d).

An example of retrieving 37

at 6.84 g of 4-Bromo-1-(chloromethyl)-3-(pentafluoroethyl)-1H-pyrazole and of 3.54 g of (3,3,3-cryptochromes)malononitrile dissolved in 60 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing between 6.08 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture is added water and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 7,15 g [(4-bromo-3-(pentafluoroethyl)-1H-pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (37) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,24-to 2.29 (2H, m), 2,49-2,61 (2H, m), and 4.75 (2H, s), 7,81 (1H, s).

An example of retrieving 38

2,90 g of the Hydrochloride of 1-(chloromethyl)-4-(trifluoromethyl)-1H-imidazole and 2,11 g of (3,3,3-cryptochromes)malononitrile dissolved in 39 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing 3,59 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1.12 g {[4-(trifluoromethyl)-1H-imidazol-1-yl]methyl}-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (38) of the present invention), the formula of which is shown below.

1N the Mrs (CDCl 3, TMS, δ (ppm)): 2,24-of 2.28 (2H, m), 2,54-to 2.65 (2H, m), a 4.53 (2H, s)to 7.50 (1H, s), 7,73 (1H, s).

An example of retrieving 39

1.70 g of 1-(Chloromethyl)-3-cyano-1H-indole and 1.45 g of (3,3,3-cryptochromes)malononitrile dissolved in 27 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing 2,49 g of potassium carbonate, followed by stirring the mixture at room temperature for 7 hours. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1.48 g [{3-cyano-1H-indol-1-yl}methyl]-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (39) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,28 of-2.32 (2H, m), of 2.51 2.63 in (2H, m), 4,78 (2H, s), 7,37-7,47 (2H, m), 7,53 (1H, d), 7,80-7,83 (2H, m).

Example of getting 40

to 3.02 g of 1-(Chloromethyl)-3-formyl-1H-indole and of 2.53 g of (3,3,3-cryptochromes)malononitrile dissolved in 45 ml of N,N-dimethylformamide. To the solution under ice cooling are added during the mixing of 4.35 g of potassium carbonate, followed by stirring the mixture at room temperature for 3 hours. To the reaction mixture, water is added and the mixture is then extracted with MT is E. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 2,68 g [{3-formyl-1H-indol-1-yl}methyl]-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (40) of the present invention), the formula of which is shown below.

1H-NMR (DMSO-d6, TMS, δ (ppm)): 2,33 is 2.51 (2H, m), 2,59 is 2.75 (2H, m), from 5.29 (2H, s), 7,30-7,40 (2H, m), of 7.97 (1H, d), 8,14 (1H, d), at 8.36 (1H, s), 10,04 (1H, s).

An example of retrieving 41

of 3.53 g of 1-(Chloromethyl)-3-(TRIFLUOROACETYL)-1H-indole and 2,19 g of (3,3,3-cryptochromes)malononitrile dissolved in 27 ml of N,N-dimethylformamide. To the solution while cooling with ice add 3,74 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining a 3.06 g [{3-(TRIFLUOROACETYL)-1H-indol-1-yl}methyl]-(3,3,3-cryptochromes)malononitrile (also called connection (41) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3 , TMS, δ (ppm)): 2,33-is 2.37 (2H, m), 2,53-to 2.65 (2H, m), is 4.85 (2H, s), 7,44 is 7.50 (2H, m), 7,52-EUR 7.57 (1H, m), 8,16 (1H, s), 8,44-of 8.47 (1H, m).

An example of retrieving 42

1,21 g [(1H-Pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (compound (1) of the present invention) is dissolved in 50 ml of acetonitrile. To the solution add 2,19 g of ammonium nitrate of cerium(IV) and of 1.02 g of iodine, followed by stirring the mixture at room temperature for 10 hours. The reaction mixture was concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1,71 g [(4-iodine-1H-pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (42) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,04-of 2.27 (2H, m), 2,48 (2H, m), 4,69 (2H, s), the 7.65 (1H, s), to 7.67 (1H, s).

An example of retrieving 43

0.21 g of 1-(Chloromethyl)-4-[(dichlorofluoromethyl)thio]-1H-pyrazole and 0.14 g of (3,3,3-cryptochromes)malononitrile dissolved in 2 ml N,N-dimethylformamide. To the solution while cooling with ice add 0.12 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered. The filtrate is concentrated under reduced pressure to thereby obtain 0.06 g of [(4-{(dichlorofluoromethyl)thio}-1H-pyrazole-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (43) of the present invention), the formula which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,24 is 2.33 (2H, m), 2.49 USD at 2.59 (2H, m), 5,43 (2H, s), 7,83 (1H, s), of 7.96 (1H, s).

An example of retrieving 44

and 0.61 g of 1-(Chloromethyl)-3-{[(dichloromethyl]thio}-1H-indole and 0.35 g of (3,3,3-cryptochromes)malononitrile dissolved in 2 ml N,N-dimethylformamide. To the solution while cooling with ice added 0.28 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0.65 g [(3-{(dichlorofluoromethyl)thio}-1H-indol-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (44) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,05-of 2.28 (2H, m), 2,49-2,60 (2H, m), 4,80 (2H, s), 7,34-7,42 (2H, m)to 7.50 (1H, d), to 7.67 (1H, s), 7,86 (1H, s).

An example of retrieving 45

and 0.61 g of 1-Chloromethyl-3-nitro-1H-pyrrole and 0.65 g of (3,3,3-cryptochromes)malononitrile dissolved in 10 ml of N,N-dimethylformamide. To the solution while cooling with ice added 0.28 g of potassium carbonate, followed by stirring the mixture at room is the temperature during the night. To the reaction mixture, water is added and the mixture is then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,80 g [(3-nitro-1H-pyrrol-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (45) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,22-of 2.26 (2H, m), 2,52-2,63 (2H, m), to 4.46 (2H, s),for 6.81-6,83 (1H, m), to 6.88 (1H, t), of 7.69 (1H, d).

An example of retrieving 46

to 0.80 g of 1-Chloromethyl-3-cyano-4-trifluoromethyl-1H-pyrrole and 0.67 g of (3,3,3-cryptochromes)malononitrile dissolved in 10 ml of N,N-dimethylformamide. To the solution under ice cooling type of 0.57 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0.33 g of [(3-cyano-4-trifluoromethyl-1H-pyrrol-1-yl)methyl]-(3,3,3-triftoruranmetilidina (denoted hereinafter compound (46) of the present invention), the formula which is shown below.

1H-NMR (DMSO-d6, TMS, δ (ppm)): 2,45 is 2.51 (2H, m), 2,62-to 2.74 (2H, m), to 4.98 (2H, s), 7,76-to 7.77 (1H, m), of 8.04 (1H, d).

An example of retrieving 47

to 0.23 g of 1-Chloromethyl-4-trifluoromethyl-3-etoxycarbonyl-1H-pyrrole and 0.15 g of (3,3,3-cryptochromes)malononitrile dissolved in 2 ml N,N-dimethylformamide. To the solution under ice cooling type of 0.13 g of potassium carbonate, followed by stirring the mixture at room temperature over night. To the reaction mixture, water is added and the mixture is then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0.20 g [(3-etoxycarbonyl-4-trifluoromethyl-1H-pyrrol-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (hereinafter referred to compound (47) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.35 (3H, t), 2.21 are of 2.26 (2H, m), 2,56-2,63 (2H, m), 4,35 (2H, square),of 4.45 (2H,s), 7,20 (1H, d), 7,53 (1H, d).

Example obtain 48

0.27 g of 1-Chloromethyl-3-cyano-1H-pyrrole and 0.34 g of (3,3,3-cryptochromes)malononitrile dissolved in 3 ml of N,N-dimethylformamide. To the solution while cooling with ice add 0,29 g is carbonate potassium, followed by stirring the mixture at room temperature for 1 hour. To the reaction mixture, water is added and the mixture is then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,37 g [(3-cyano-1H-pyrrol-1-yl)methyl]-(3,3,3-cryptochromes)malononitrile (denoted hereinafter compound (48) of the present invention), the formula of which is shown below.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,18-of 2.23 (2H, m), 2,46-of 2.64 (2H, m), to 4.46 (2H, s), 6,58-6,59 (1H, m), 6.87 in-to 6.88 (1H, m), 7,33-to 7.35 (1H, m).

Further illustrated reference examples of the preparation of the intermediate compounds.

Reference example obtaining 1-1

1H-pyrazole-1-ylmethanol

The mixture 2,04 g of pyrazole, from 2.00 g of paraformaldehyde and 1 ml of triethylamine was stirred at 130°C for 10 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone and the mixture is then filtered. The filtrate is concentrated under reduced pressure. To the residue add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving 3,10 g 1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): the 5.51 (2H, s), 6,30 (1H, t), 7,587,61 (2H, m).

Reference example get 1-2

Hydrochloride of 1-(chloromethyl)-1H-pyrazole

3,10 g 1H-pyrazole-1-ylmethanol dissolved in 100 ml of dichloromethane. To the solution was added 6.8 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure. The residue is recrystallized from a mixture of hexane-chloroform, while receiving 2.66 g of the hydrochloride of 1-(chloromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 5,91 (2H, s)6,38 (1H, t), to 7.61-to 7.68 (2H, m).

Reference example obtaining 2-1

3-Isopropyl-1H-pyrazole

In nitrogen atmosphere, the mixture 17,23 g isopropylethylene and 12,01 g methylformate cooled to 0°C and then to the mixture over a period of 1 hour type of 22.44 g of tert-butoxide potassium, dissolved in 200 ml of tetrahydrofuran. During the addition the temperature of the mixture kept lower than 20°C. then the reaction mixture was stirred at 30°C for 5 hours. To the reaction mixture, which is cooled to room temperature, add 200 ml of diethyl ether, the resulting solid substance. The solid is collected by filtration and washed with 20 ml of diethyl ether. The obtained solid is dried under reduced pressure, thus obtaining 14,14 g of potassium salt of 1-Ki-the Roxy-4-methyl-1-penten-3-one. 14,14 g of potassium salt of 1-hydroxy-4-methyl-1-penten-3-one are suspended in 90 ml of ethanol. To a suspension type of 5.11 g of hydrazine hydrate and the mixture is refluxed for 7 hours. To the reaction mixture, which is cooled to room temperature, add 30 ml of water and the mixture is concentrated to 30 ml under reduced pressure. The residue is extracted with ethyl acetate. The organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 6,83 g of 3-isopropyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,29 (6N, e), 3,01-is 3.08 (1H, m), 6,10 (1H, s), 7,49 (1H, s).

Reference example obtaining 2-2

3-Isopropyl-1H-pyrazole-1-ylmethanol

A mixture of 1.15 g of 3-isopropyl-1H-pyrazole, 0,94 g of paraformaldehyde and 0.14 g of triethylamine was stirred at 130°C for 7 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure. To the residue add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving 1.28 g of 3-isopropyl-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,24 (6N, e), 2,94-to 3.02 (1H, m), of 5.48 (2H, s), 6,10 (1H, d), 7,47 (1H, d).

Reference example get 2-3

Hydrochloride 3-isopropyl-1-(chloromethyl)-1H-pyrazole

1.28 g of 3-Isopropyl-1H-pyrazole-1-ylmethanol dissolved in 20 ml of dichloromethane. To the solution add 2 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining 1,58 g of the hydrochloride of 3-isopropyl-1-(chloromethyl)-1H-pyrazole.

Reference example obtaining 3-1

3-tert-Butyl-1H-pyrazole

Under nitrogen atmosphere a mixture of 50.00 g of pinacolone and 42,00 g methylformate cooled to 0°C and then to the mixture over a period of 3 hours add 56,00 g of tert-butoxide potassium. During the addition the temperature of the mixture kept lower than 20°C. then the reaction mixture was stirred at 30°C for 5 hours. To the reaction mixture, which is cooled to room temperature, add diethyl ether, the resulting solid substance. The solid is collected by filtration and dried under reduced pressure, thus obtaining 32,12 g of potassium salt of 1-hydroxy-4,4-dimethyl-1-penten-3-one. 21,61 g of potassium salt of 1-hydroxy-4,4-dimethyl-1-penten-3-one are suspended in 150 ml of ethanol. To a suspension type of 6.52 g of hydrazine hydrate and the mixture is then refluxed for 7 cha is impressive. To the reaction mixture, which is cooled to room temperature, add 50 ml of water and the mixture is concentrated to 40 ml under reduced pressure. A concentrated solution is extracted with ethyl acetate. The organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 6,83 g of 3-tert-butyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,34 (N, C), 6,11 (1H, d), 7,47 (1H, d).

Reference example obtaining 3-2

3-tert-Butyl-1H-pyrazole-1-ylmethanol

A mixture of 1.28 g of 3-tert-butyl-1H-pyrazole, 0.66 g of paraformaldehyde and 0.3 g of triethylamine was stirred at 130°C for 7 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure. To the residue add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving 1.07 g of 3-tert-butyl-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1.28 (in N, (C), of 5.50 (2H, s), 6,13 (1H, s), 7,46 (1H, s).

Reference example obtaining 3-3

Hydrochloride 3-tert-butyl-1-(chloromethyl)-1H-pyrazole

1.07 g of 3-tert-Butyl-1H-pyrazole-1-ylmethanol dissolved in 140 m is dichloromethane. To the solution add 2 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining 1.66 g of the hydrochloride of 3-tert-butyl-1-(chloromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 6.25 (2H, s)6,40 (1H, d), of 7.69 (1H, d).

Reference example obtaining 4-1

6,6-Dimethyl-2,4,5,6-tetrahydrocyclopent[c]pyrazole

In nitrogen atmosphere, the mixture 12,22 g of 2,2-dimethylcyclopentane and 6,01 g methylformate cooled to 0°C and then to the mixture over a period of 1 hour add 6,74 g of tert-butoxide potassium. During the addition the temperature of the mixture kept lower than 20°C. then the reaction mixture was stirred at room temperature for 18 hours. To the reaction mixture is added diethyl ether, the resulting solid substance. The solid is collected by filtration. The obtained solid is dried under reduced pressure, thus obtaining 9,94 g of potassium salt of 1-hydroxymethyl-5,5-dimethylcyclopentane. 9,94 g of potassium salt of 1-hydroxymethyl-5,5-dimethylcyclopentane suspended in 80 ml of ethanol. To a suspension add 2,80 g of hydrazine hydrate and the mixture is then refluxed for 5 hours. To the reaction mixture, which is cooled down to room temperature is, add 50 ml of water and the mixture is concentrated to 40 ml under reduced pressure. A concentrated solution is extracted with ethyl acetate. The organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1.68 g of 6,6-dimethyl-2,4,5,6-tetrahydrocyclopent[c]pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,32 (6N, (C), 2,23-of 2.28 (2H, t), 2,60-of 2.64 (2H, t), 7,11 (1H, s).

Reference example obtaining 4-2

{6,6-Dimethyl-5,6-dihydrocyclopenta[c]pyrazole-2(4H)-yl}methanol

A mixture of 1.68 g of 6,6-dimethyl-2,4,5,6-tetrahydrocyclopent[c]pyrazole, 0,41 g of paraformaldehyde and 0.2 g of triethylamine was stirred at 130°C for 5 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure. To the residue add hexane, resulting in the formation of the crystalline substance. Crystalline material is collected, while receiving 0.31 g {6,6-dimethyl-5,6-dihydrocyclopenta[c]pyrazole-2(4H)-yl}methanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,28 (6N, C)to 2.18 (2H, t), at 2.59 (2H, t), 5,44 (2H, s), 7,13 (1H, s).

Reference example obtaining 4-3

Hydrochloride of 1-(chloromethyl)-6,6-dimethyl-5,6-dihydrocyclopenta[c]pyrazole

0.31 g (6,6-Dimethyl-5,6-dihydrocyclopenta[c]pyrazole-2(4H)-yl}methanol dissolved in 5 ml dichloromethane. To the solution add 1 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining of 0.58 g of the hydrochloride of 1-(chloromethyl)-6,6-dimethyl-5,6-dihydrocyclopenta[c]pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,46 (6N, (C), of 2.33 (2H, t), by 2.73 (2H, t), 6,18 (2H, s), 7,45 (1H, s).

Reference example obtaining 5-1

3-(Trifluoromethyl)-1H-pyrazole-1-ylmethanol

The mixture 4,08 g 3-(trifluoromethyl)-1H-pyrazole, from 2.00 g of paraformaldehyde and 1 ml of triethylamine was stirred at 80°C for 5 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure. To the residue add hexane, resulting in the formation of the crystalline substance. Crystalline material is collected, while receiving or 4.31 g of 3-(trifluoromethyl)-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): to 4.73 (1H, user. C)to 5.58 (2H, s), to 6.58 (1H, s), 7,66 (1H, s).

Reference example obtaining 5-2

1-(Chloromethyl)-3-(trifluoromethyl)-1H-pyrazole

of 1.33 g of 3-(Trifluoromethyl)-1H-pyrazole-1-ylmethanol dissolved in 40 ml of dichloromethane. K R is the target type of 2.7 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining 1.44 g of 1-(chloromethyl)-3-(trifluoromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 5,88 (2H, s), 6,62 (1H, d), to 7.68 (1H, d).

Reference example obtaining 6-1

1-(Hydroxymethyl)-3-formyl-1H-pyrazole

A mixture of 0.96 g of 3-formyl-1H-pyrazole, of 0.60 g of paraformaldehyde and 0.3 ml of triethylamine was stirred at 100°C for 5 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure, thus obtaining 1,21 g of 1-(hydroxymethyl)-3-formyl-1H-pyrazole. The crude product used in the next process without purification.

1H-NMR (CDCl3, TMS, δ (ppm)): 5,63 (2H, s), at 6.84 (1H, d), to 7.67 (1H, d), 9,96 (1H, s).

Reference example obtaining 6-2

Hydrochloride of 1-(chloromethyl)-3-formyl-1H-pyrazole

to 1.21 g of 1-(Hydroxymethyl)-3-formyl-1H-pyrazole are dissolved in 50 ml of dichloromethane. To the solution was added 2.4 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining of 1.57 g of the hydrochloride of 1-(chloromethyl)-3-formyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 5.92 (2H, s), to 6.88 (1H, s), to 7.67 (1H, s), 10,00 (1H, s).

Reference the example of obtaining 7-1

3-Cyano-1H-pyrazole

of 2.18 g of 3-Formyl-1H-pyrazole are dissolved in 12 ml of pyridine. To the solution add 1,58 g of hydroxylamine hydrochloride, followed by stirring at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure. To the residue add 30 ml of acetic anhydride, followed by stirring at 100°C for 5 hours. After cooling the reaction mixture to room temperature it concentrated under reduced pressure. To the residue add 30 ml of ethanol and the mixture is then stirred at 100°C for 3 hours. After cooling the reaction mixture to room temperature it concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,86 g 3-cyano-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 6,79 (1H, d), of 7.75 (1H, d).

Reference example obtaining 7-2

1-(Hydroxymethyl)-3-cyano-1H-pyrazole

The mixture 0,86 g 3-cyano-1H-pyrazole and 0.55 g of paraformaldehyde was stirred at 130°C for 7 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. After filtration of the mixture, the filtrate is concentrated under reduced pressure, thus obtaining 0,89 g of 1-(hydroxymethyl)-3-cyano-1H-pyrazole.

1H-NMR, DMSO-d 6, TMS, δ (ppm)): 5,54 (2H, s)6,70 (1H, d), 7,72 (1H, d).

Reference example obtaining 7-3

3-Cyano-1-(chloromethyl)-1H-pyrazole

0,89 g of 1-(Hydroxymethyl)-3-cyano-1H-pyrazole are dissolved in 30 ml of dichloromethane. To the solution was added 1.6 ml of thionyl chloride, followed by stirring at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining a 1.00 g of 3-cyano-1-(chloromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): by 5.87 (2H, s)6,76 (1H, s), 7,72 (1H, s).

Reference example receive 8-1

3-Phenyl-1H-pyrazole-1-ylmethanol

The mixture is 2.88 g of 3-phenyl-1H-pyrazole, of 0.67 g of paraformaldehyde and 0.3 ml of triethylamine was stirred at 130°C for 5 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. After filtration of the mixture to the filtrate add hexane for the formation of crystalline substances. Crystalline material is collected, while receiving 2.64 g of 3-phenyl-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 5.56mm (2H, s), to 6.58 (1H, d), 7,31-7,42 (3H, m), to 7.59 (1H, d), 7,76-7,79 (2H, m).

Reference example obtaining 8-2

Hydrochloride of 1-(chloromethyl)-3-phenyl-1H-pyrazole

of 1.74 g of 3-Phenyl-1H-pyrazole-1-ylmethanol dissolved in 50 ml of dichloromethane. RA is Toru add 3.4 ml of thionyl chloride, followed by stirring at room temperature over night. The reaction mixture was concentrated under reduced pressure. To the residue add hexane and chloroform to obtain a crystalline substance. Crystalline material is collected, while receiving a 2.01 g of the hydrochloride of 1-(chloromethyl)-3-phenyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): x 6.15 (2H, s)6,76 (1H, d), 7,39-7,49 (3H, m), 7,76 (1H, d), of 7.90-7,94 (2H, m).

Reference example obtaining 9-1

4-Bromo-3-isopropyl-1H-pyrazole

1.10 g of 3-isopropyl-1H-pyrazole suspended in 20 ml of water and the suspension added to 1.6 g of 50% aqueous sodium hydroxide solution. The mixture is cooled to 0°C and then added to the mixture of 1.76 g of bromine, followed by stirring the mixture at room temperature for 5 hours. The reaction mixture was extracted with ethyl acetate. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1.88 g of 4-bromo-3-isopropyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,31 (6N, e), 3,07-3,18 (1H, m), 7,49 (1H, c),

Reference example get 9-2

4-Bromo-3-isopropyl-1H-pyrazole-1-ylmethanol

A mixture of 1.88 g of 4-bromo-3-isopropyl-1H-pyrazole, of 0.60 g of paraformaldehyde and 0.10 g of triethylamine was stirred at 130°C for 5 hours. After cooling, actionnow mixture to room temperature, to the reaction mixture acetone. The mixture is filtered and the filtrate concentrated under reduced pressure, thus obtaining 1.29 g of 4-bromo-3-isopropyl-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,26 (6N, e), 3,02-3,11 (1H, m), 5,43 (2H, s), 7,54 (1H, s).

Reference example get 9-3

The hydrochloride of 4-bromo-3-isopropyl-1-(chloromethyl)-1H-pyrazole

1.29 g of 4-Bromo-3-isopropyl-1H-pyrazole-1-ylmethanol dissolved in 20 ml of dichloromethane. To the solution add 2 ml of thionyl chloride, followed by stirring at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining 1.28 g of the hydrochloride of 4-bromo-3-isopropyl-1-(chloromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,29 (6N, e), 2,99-3,10 (1H, m),of 5.75 (2H, s), 7,54 (1H, s).

Reference example 10-1 receiving

4-Bromo-3-tert-butyl-1H-pyrazole

2,48 g of 3-tert-Butyl-1H-pyrazole suspended in 35 ml of water and the suspension added 2.5 g of 50% aqueous sodium hydroxide solution. The mixture is cooled to 0°C and then added to the mixture of 3.50 g of bromine, followed by stirring at room temperature for 7 hours. The reaction mixture was extracted with ethyl acetate. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is subjected to column items is matography on silica gel, while receiving 3,14 g of 4-bromo-3-tert-butyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,45 (N, C)of 7.48 (1H, s).

Reference example obtaining 10-2

4-Bromo-3-tert-butyl-1H-pyrazole-1-ylmethanol

A mixture of 3.14 g of 4-bromo-3-tert-butyl-1H-pyrazole, with 0.93 g of paraformaldehyde and 0.11 g of triethylamine was stirred at 130°C for 7 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. To the residue obtained by concentration of the filtrate under reduced pressure, add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving 3,79 g of 4-bromo-3-tert-butyl-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,37 (N, C)of 5.40 (2H, s), 7,55 (1H, s).

Reference example obtaining 10-3

The hydrochloride of 4-bromo-3-tert-butyl-1-(chloromethyl)-1H-pyrazole

with 3.79 g of 4-Bromo-3-tert-butyl-1H-pyrazole-1-ylmethanol dissolved in 45 ml of dichloromethane. To the solution was added 3.4 ml of thionyl chloride, followed by stirring at room temperature over night. The reaction mixture was concentrated under reduced pressure. The obtained solid is washed with hexane and chloroform, while receiving of 3.69 g of the hydrochloride of 4-bromo-3-tert-butyl-1-(chloromethyl)-1H-pyrazole is.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,40 (N,), USD 5.76 (2H, s), 7,56 (1H, s).

Reference example obtaining 11-1

3-tert-Butyl-4-chloro-1H-pyrazole

1.42 g of 3-tert-Butyl-1H-pyrazole are dissolved in 230 ml of chloroform. To the solution was added 1.55 g of N-chlorosuccinimide, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure and the residue is subjected to column chromatography on silica gel, thus obtaining of 0.62 g of 3-tert-butyl-4-chloro-1H-pyrazole.

Reference example get 11-2

3-tert-Butyl-4-chloro-1H-pyrazole-1-methanol

A mixture of 0.62 g of 3-tert-butyl-4-chloro-1H-pyrazole, 0.24 g of paraformaldehyde and 0.10 g of triethylamine was stirred at 130°C for 7 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. To the residue obtained by concentration of the filtrate under reduced pressure, add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving of 0.82 g of 3-tert-butyl-4-chloro-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,38 (N, C)of 5.39 (2H, s), 7,51 (1H, s).

Reference example get 11-3

Hydrochloride 3-tert-butyl-4-chloro-1-(chloromethyl)-1H-pyrazole

of 0.82 g of 3-tert-Butyl-4-chloro-1H-pyrazole-1-ylmethanol dissolved in 45 ml of dichloromethane. To the solution was added 3.4 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining 0,98 g of the hydrochloride of 3-tert-butyl-4-chloro-1-(chloromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,39 (N, (C), of 5.75 (2H, s), 7,52 (1H, s).

Reference example obtaining 12-1

4-Bromo-3-(trifluoromethyl)-1H-pyrazole

3.50 g of 3-(Trifluoromethyl)-1H-pyrazole suspended in 45 ml of water and the suspension added 3.2 g of 50% aqueous sodium hydroxide solution. The mixture is cooled to 0°C and then added to the mixture 3,20 g of bromine, followed by stirring at room temperature for 7 hours. The reaction mixture was extracted with ethyl acetate. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. To the residue add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving to 3.38 g of 4-bromo-3-(trifluoromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 7,72 (1H, s).

Reference example get 12-2

4-Bromo-3-(trifluoromethyl)-1H-pyrazole-1-ylmethanol

The mixture stood at 3.38 g of 4-bromo--(trifluoromethyl)-1H-pyrazole and 0.66 g of paraformaldehyde was stirred at 140°C for 5 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. To the residue obtained by concentration of the filtrate under reduced pressure, add hexane, resulting receive a crystalline substance. Crystalline material is collected, while receiving of 3.28 g of 4-bromo-3-(trifluoromethyl)-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 5,52 (2H, s), 7,71 (1H, s).

Reference example get 12-3

4-Bromo-1-(chloromethyl)-3-(trifluoromethyl)-1H-pyrazole

of 3.28 g of 4-Bromo-3-(trifluoromethyl)-1H-pyrazole-1-ylmethanol dissolved in 40 ml of dichloromethane. To the solution was added to 2.9 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure. The obtained solid is washed with a mixture of hexane and chloroform, while receiving 3.33 g of 4-bromo-1-(chloromethyl)-3-(trifluoromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 5.82 (2H, s), 7,74 (1H, s).

Reference example get 13

Hydrochloride of 1-(chloromethyl)for 3,5-dimethylpyrazole

0,63 g of 3,5-Dimethyl-1H-pyrazole-1-ylmethanol dissolved in 25 ml of dichloromethane. To the solution was added 1.2 ml of thionyl chloride, followed by stirring the mixture at room temperature during the course the e night. The reaction mixture was concentrated under reduced pressure, thus obtaining 0,93 g of the hydrochloride of 1-(chloromethyl)for 3,5-dimethyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,49 (3H, s)of 2.50 (3H, s), of 6.20 (3H, s).

Reference example get 14-1

4-Methyl-1H-pyrazole-1-ylmethanol

A mixture of 1.93 g of 4-methyl-1H-pyrazole, 0.97 g of paraformaldehyde and 0.4 ml of triethylamine was stirred at 130°C for 5 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. To the residue obtained by concentration of the filtrate under reduced pressure, add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving 1,72 g of 4-methyl-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 2,08 (3H, s), 5,43 (2H, s), of 7.36 (2H, s).

Reference example get 14-2

Hydrochloride of 1-(chloromethyl)-4-methyl-1H-pyrazole

1.12 g of 4-methyl-1H-pyrazole-1-ylmethanol dissolved in 50 ml of dichloromethane. To the solution was added 3.4 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining of 1.61 g of the hydrochloride of 1-(chloromethyl)-4-methyl-1H-pyrazole.

Reference example obtaining 5-1

4-Chloro-1H-pyrazole-1-ylmethanol

A mixture of 2.05 g of 4-chloropyrazole, 0.66 g of paraformaldehyde and 0.11 g of triethylamine was stirred at 130°C for 5 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. To the residue obtained by concentration of the filtrate under reduced pressure, add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving 2,73 g of 4-chloro-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): the 5.45 (2H, s), 7,49 (1H, s), 7,60 (1H, s).

Reference example get 15-2

Hydrochloride 4-chloro-1-(chloromethyl)-1H-pyrazole

2,73 g of 4-Chloro-1H-pyrazole-1-ylmethanol dissolved in 20 ml of dichloromethane. To the solution was added to 4.4 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining 2,90 g of the hydrochloride of 4-chloro-1-(chloromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 5.81 (2H, s), 7,53 (1H, s), 7,60 (1H, s).

Reference example obtaining 16-1

4-Bromo-1H-pyrazole-1-ylmethanol

The mixture 2,94 g of 4-bromo-1H-pyrazole, 0.66 g of paraformaldehyde and 0.3 ml of triethylamine was stirred at 130°C in techenie hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. To the residue obtained by concentration of the filtrate under reduced pressure, add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving 2,97 g of 4-bromo-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 5,46 (2H, s), 7,53 (1H, s), 7,63 (1H, s).

Reference example get 16-2

The hydrochloride of 4-bromo-1-(chloromethyl)-1H-pyrazole

of 2.97 g of 4-Bromo-1H-pyrazole-1-ylmethanol dissolved in 100 ml of dichloromethane. To the solution add 5 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining of 3.27 g of the hydrochloride of 4-bromo-1-(chloromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 5.83 (2H, s), EUR 7.57 (1H, s), 7,63 (1H, s).

Reference example get 17-1

4-(Trifluoromethyl)-1H-pyrazole

The above compound is produced by a method described in Tetrahedron Letters of 1829 (1996).

Reference example get 17-2

4-(Trifluoromethyl)pyrazole-1-yl-1H-methanol

A mixture of 0.59 g of 4-(trifluoromethyl)-1H-pyrazole and 0.26 g of paraformaldehyde was stirred at 130°C in those who tell 4 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure, thus obtaining of 0.60 g of 4-(trifluoromethyl)-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): to 5.58 (2H, s), to 7.77 (1H, s), of 7.90 (1H, s).

Reference example get 17-3

1-(Chloromethyl)-4-(trifluoromethyl)-1H-pyrazole

of 0.60 g of 4-(Trifluoromethyl)-1H-pyrazole-1-ylmethanol dissolved in 10 ml of dichloromethane. To the solution add 1 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining of 0.60 g of 4-(chloromethyl)-1-(trifluoromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 5.89 (2H, s), 7,80 (1H, s), to $ 7.91 (1H, s).

Reference example get 18-1

4-Methoxycarbonyl-1H-pyrazole

44,45 g of Methyl-3,3-dimethoxypropionate and 45 ml of methylformate dissolved in 180 ml of dimethoxyethane. To a solution under nitrogen atmosphere add 12.8 g of 60% sodium hydride, maintaining the temperature of the solution during the addition of 40-50°C. the mixture is Then stirred at room temperature for 18 hours. To the reaction mixture add 180 ml of diethyl ether, the resulting solid substance. Solid Sobir the Ute by filtration followed by washing his 60 ml of diethyl ether. The obtained solid is dried under reduced pressure over night, while receiving 49,41 g of sodium salt of methyl 2-(dimethoxymethyl)-3-hydroxyacrylates. to 9.91 g of sodium salt of methyl 2-(dimethoxymethyl)-3-hydroxyacrylates suspended in 100 ml of ethanol. To the suspension is added 2.50 g of hydrazine hydrate, followed by stirring the mixture at room temperature for 3 hours and at 80°C for 1 hour. To the reaction mixture was added 100 ml of water, the mixture is cooled to room temperature. The mixture is concentrated under reduced pressure to approximately 100 ml Concentrated solution is extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue is dissolved in ethyl acetate, the solution was added activated charcoal and stirred over night. The suspension is filtered. The filtrate is concentrated under reduced pressure. The residue is recrystallized from a mixture of hexane-ethyl acetate, thus obtaining 1.40 g of 4-methoxycarbonyl-1H-pyrazole.

1H-NMR (DMSO-d6, TMS, δ (ppm)): 3,74 (3H, s), 8,08 (2H, s), 13,43 (1H, s).

Reference example get 18-2

1-(Hydroxymethyl)-4-methoxycarbonyl-1H-pyrazole

A mixture of 1.40 g of 4-methoxycarbonyl-1H-pyrazole, 0,37 g paraf is maldehyde and 0.11 g of triethylamine was stirred at 130°C for 1 hour. To the mixture of 0.74 g of paraformaldehyde and 2 ml of triethylamine and the mixture is stirred at 130°C for 2 hours. After cooling the reaction mixture to room temperature, add acetone. After filtration of the mixture, the filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1,38 g of 1-(hydroxymethyl)-4-methoxycarbonyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): a-3.84 (3H, s), of 5.53 (2H, s), of 7.96 (1H, s), 8,08 (1H, s).

Reference example get 18-3

1-(Chloromethyl)-4-methoxycarbonyl-1H-pyrazole

to 1.38 g of 1-(Hydroxymethyl)-4-methoxycarbonyl-1H-pyrazole was dissolved in 10 ml of dichloromethane. To the solution add 1 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining 1,59 g of 1-(chloromethyl)-4-methoxycarbonyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 3.85 (3H, s), to 5.85 (2H, s), 7,98 (1H, s), 8,10 (1H, s).

Reference example get 19-1

1-(Hydroxymethyl)-3-(trifluoromethyl)-4-etoxycarbonyl-1H-pyrazole

A mixture of 2.08 g of 3-(trifluoromethyl)-4-etoxycarbonyl-1H-pyrazole and 0.66 g of paraformaldehyde was stirred at 150°C for 4 hours. After cooling the reaction mixture to room temperature on billaut acetone. After filtration of the mixture, the filtrate is concentrated under reduced pressure, thus obtaining of 2.23 g of 1-(hydroxymethyl)-3-(trifluoromethyl)-4-etoxycarbonyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 1.34 (3H, t), 4,30 (2H, HF), to 5.58 (2H, s), 8,21 (1H, s).

Reference example get 19-2

1-(Chloromethyl)-3-(trifluoromethyl)-4-etoxycarbonyl-1H-pyrazole

of 2.23 g of 1-(Hydroxymethyl)-3-(trifluoromethyl)-4-etoxycarbonyl-1H-pyrazole are dissolved in 30 ml of dichloromethane. To the solution was added to 1.4 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining of 2.38 g of 1-(chloromethyl)-3-(trifluoromethyl)-4-etoxycarbonyl-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,31 (3H, t), or 4.31 (2H, square), to 5.85 (2H, s), to 8.20 (1H, s).

Reference example receive 20

Hydrochloride of 1-chloromethyl-1H-1,2,4-triazole

The above compound is produced by a method described in JP S57-165374 A.

1H-NMR (DMSO-d6, TMS, δ (ppm)): of 6.26 (2H, s), 8,16 (1H, s), cent to 8.85 (1H, s).

Reference example get 21-1

3-Isopropyl-1H-1,2,4-triazole

The above compound is obtained by the method similar to the method described in JP h6-87839 A.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,39 (6N, e), 3,14-3,74 (1H m), to 7.99 (1H, s).

Reference example get 21-2

3-Isopropyl-1H-1,2,4-triazole-1-ylmethanol

A mixture of 1.15 g of 3-isopropyl-1H-1,2,4-triazole, of 0.94 g of paraformaldehyde and 0.14 g of triethylamine is stirred at 150°C for 5 hours. After cooling the reaction mixture to room temperature, add acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure. To the obtained residue, add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving 1.28 g of 3-isopropyl-1H-triazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,32 (6N, d), 3.04 from-of 3.12 (1H, m)5,54 (2H, s)to 8.14 (1H, s).

Reference example get 21-3

Hydrochloride of 1-(chloromethyl)-3-isopropyl-1H-1,2,4-triazole

1.28 g of 3-Isopropyl-1H-1,2,4-triazole-1-ylmethanol dissolved in 20 ml of dichloromethane and to the solution add 2 ml of thionyl chloride, followed by stirring the mixture at room temperature for 8 hours. The reaction mixture was concentrated under reduced pressure. To the residue is added diethyl ether, resulting in a crystalline substance. Crystalline material is collected, while receiving 1,58 g of the hydrochloride of 1-(chloromethyl)-3-isopropyl-1H-1,2,4-triazole.

Reference example get 22-1

3-tert-Butyl-1H-1,2,4-reasol

The above compound is produced by a method described in JP h6-87839 A.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,45 (N, C)of 8.25 (1H, s).

Reference example get 22-2

3-tert-Butyl-1H-1,2,4-triazole-1-ylmethanol

The mixture 3,76 g of 3-tert-butyl-1H-1,2,4-triazole, and 1.00 g of paraformaldehyde and 0.3 ml of triethylamine was stirred at 150°C for 5 hours. After cooling the reaction mixture to room temperature, add acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure. To the obtained residue, add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving to 1.38 g of 3-tert-butyl-1H-triazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,37 (N, C), is 1.81 (1H, user. C)of 5.55 (2H, s), 8,16 (1H, s).

Reference example get 22-3

Hydrochloride 3-tert-butyl-1-(chloromethyl)-1H-1,2,4-triazole

A mixture of 1.38 g of 3-tert-butyl-1H-1,2,4-triazole-1-ylmethanol and 2.7 ml of thionyl chloride is stirred under conditions of boiling under reflux for 3 hours. After cooling the reaction mixture to room temperature, the reaction mixture was concentrated under reduced pressure. The residue is recrystallized from hexane, thus obtaining 1,72 g of the hydrochloride of 3-tert-butyl-1-(PI is rmutil)-1H-1,2,4-triazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,36 (N, C)of 5.83 (2H, s), 8,17 (1H, s).

Reference example get 23-1

3-(1,1-Dimethylpropyl)-1H-1,2,4-triazole

The above compound is obtained by the method similar to the method described in JP h6-87839 A.

1H-NMR (CDCl3, TMS, δ (ppm)): 0,77 (3H, t), 1,40 (6N, (C), of 1.74 (2H, square), 7,98 (1H, s).

Reference example get 23-2

3-(1,1-Dimethylpropyl)-1H-1,2,4-triazole-1-ylmethanol

The mixture 0,86 g of 3-(1,1-dimethylpropyl)-1H-1,2,4-triazole, and 0.37 g of paraformaldehyde and 0.63 g of triethylamine is stirred at 150°C for 5 hours. After cooling the reaction mixture to room temperature, add acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure, to thereby obtain 1.10 g of 3-(1,1-dimethylpropyl)-1H-triazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 0,73 (3H, t), 1,33 (6N, C)1,71 (2H, square), 5,54 (2H, s), 8,16 (1H, s).

Reference example get 23-3

Hydrochloride of 1-(chloromethyl)-3-(1,1-dimethylpropyl)-1H-1,2,4-triazole

1.10 g of 3-(1,1-Dimethylpropyl)-1H-1,2,4-triazole-1-ylmethanol dissolved in 18 ml of dichloromethane. To the solution was added 1.8 ml of thionyl chloride, followed by stirring the mixture at room temperature for 8 hours. The reaction mixture was concentrated under reduced pressure, while this is 1.47 g of the hydrochloride of 1-(chloromethyl)-3-(1,1-dimethylpropyl)-1H-1,2,4-triazole.

Reference example get 24-1

5-Bromo-3-tert-butyl-1H-1,2,4-triazole

A mixture of 2.51 g of 3-tert-butyl-1H-1,2,4-triazole, 35 ml of water and 2.5 ml of 50% aqueous sodium hydroxide solution cooled to 0°C, then added to the mixture of 3.5 g of bromine. The mixture is stirred at room temperature for 3 hours. The reaction mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is recrystallized from hexane, to thereby obtain 3.80 g of 5-bromo-3-tert-butyl-1H-1,2,4-triazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,41 (N, C)11,60 (1H, user. C).

Reference example get 24-2

5-Bromo-3-tert-butyl-1H-1,2,4-triazole-1-ylmethanol

A mixture of 3.45 g of 5-bromo-3-tert-butyl-1H-1,2,4-triazole, and 0.61 g of paraformaldehyde and 0.17 ml of triethylamine was stirred at 130°C for 5 hours. After cooling the reaction mixture to room temperature, add acetone. The mixture is filtered. To the residue add hexane and the mixture is filtered. The filtrate is concentrated under reduced pressure, thus obtaining 2,88 g of 5-bromo-3-tert-butyl-1H-1,2,4-triazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 1,34 (N, C)of 5.55 (2H, s).

Reference example get 24-3

Hydrochloride, 5-bromo-3-tert-butyl-1-(chloromethyl)-1H-1,2,4-triazole

1H-NMR (CDCl3, TMS, δ (ppm)): 1,35 (N, C), 5,79 (2H, s).

Reference example obtaining 25-1

3-(Trifluoromethyl)-1H-1,2,4-triazole

value of 4.76 g of hydrazine hydrate are dissolved in 160 ml of ethanol and the solution cooled to 0°C. To the solution over a period of 30 minutes added dropwise 14,21 g ethyl-2,2,2-triptoreline, followed by stirring the mixture at 0°C for 1 hour. To the reaction mixture of 9.89 g of salt formamidinesulfinic acid, followed by stirring the mixture at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure. To the residue is added 200 ml of acetic acid, followed by stirring the mixture at 100°C for 5 hours. The reaction mixture, which is cooled to room temperature, concentrated under reduced pressure. To the residue is added saturated aqueous sodium hydrogen carbonate solution to establish a pH of 6. Then the solution is extracted with ethyl acetate. Organic the sky layer is dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is recrystallized from hexane, thus obtaining 5,44 g 3-(trifluoromethyl)-1H-1,2,4-triazole.

1H-NMR (CDCl3, TMS, δ (ppm)): to 8.45 (1H, s), 12,47 (1H, user. C).

Reference example get 25-2

3-(Trifluoromethyl)-1H-1,2,4-triazole-1-ylmethanol

The mixture is 2.74 g of 3-(trifluoromethyl)-1H-1,2,4-triazole and 1.20 g of paraformaldehyde was stirred at 150°C for 5 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone and the mixture is filtered. The filtrate is concentrated. The residue is subjected to column chromatography on silica gel, thus obtaining 3,15 g 3-(trifluoromethyl)-1H-1,2,4-triazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): Android 4.04 (1H, t), 5,67 (2H, d), of 8.37 (1H, s).

Reference example get 25-3

1-(Chloromethyl)-3-(trifluoromethyl)-1H-1,2,4-triazole

1.52 g of 5-(trifluoromethyl)-1H-1,2,4-triazole-1-ylmethanol dissolved in 50 ml of dichloromethane and to the solution was added to 2.7 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining of 1.36 g of 1-(chloromethyl)-3-(trifluoromethyl)-1H-1,2,4-triazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 5.92 (2H, s), 8,44 (1H, s).

Reference example get 26-1

3-(Pentafluoroethyl)-1H-1,2,4-triazole

1,25 g of hydrazine Hydrate are dissolved in 45 ml of ethanol and the solution cooled to 0°C. To the solution over a period of 15 minutes is added dropwise 5,38 g ethyl-2,2,3,3,3-pentafluoropropionate, followed by stirring at 0°C for 1 hour. To the reaction mixture add 2,61 g of salt formamidinesulfinic acid, followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure. To the residue are added 50 ml of acetic acid, followed by stirring at 100°C for 5 hours. The reaction mixture was concentrated under reduced pressure. To the residue is added saturated aqueous sodium hydrogen carbonate solution so as to achieve a pH of approximately 6. The solution is then extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 2,98 g 3-pentafluoroethyl-1H-1,2,4-triazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 8.47 (1H, s), KZT 12.39 (1H, user. C).

Reference example get 26-2

3-(Pentafluoroethyl)-1H-1,2,4-triazole-1-ylmethanol

A mixture of 1.45 g of 3-(pentafluoropropyl)-1H-1,2,4-triazole and 0.46 g of paraformaldehyde was stirred at 150°C for 5 hours. After cooling the reaction mixture to room temperature before ablaut acetone. The mixture is filtered. The filtrate is concentrated. To the residue add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving 1.52 g of 3-(pentafluoroethyl)-1H-1,2,4-triazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): 5,69 (2H, s), to 8.41 (1H, s).

Reference example get 26-3

1-(Chloromethyl)-3-(pentafluoroethyl)-1H-1,2,4-triazole

1.52 g of 3-(Pentafluoropropyl)-1H-1,2,4-triazole-1-ylmethanol dissolved in 50 ml of dichloromethane and to the solution was added to 2.7 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining of 1.36 g of 1-(chloromethyl)-3-(pentafluoropropyl)-1H-1,2,4-triazole.

1H-NMR (CDCl3, TMS, δ (ppm)): to 5.93 (2H, s), 8,44 (1H, s).

Reference example get 27-1

3-(Pentafluoroethyl)-1H-pyrazole-1-ylmethanol

A mixture of 1.86 g of 3-(pentafluoropropyl)-1H-pyrazole and of 0.60 g of paraformaldehyde was stirred at 130°C for 5 hours. After cooling the reaction mixture to room temperature, add acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure, to thereby obtain 1.98 g of 3-(pentafluoropropyl)-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): of 4.54 (1H, user. C)to 5.58 (2H, d), 6,60 (1H, d), to 7.68 (1H, is).

Reference example get 27-2

1-(Chloromethyl)-3-(pentafluoroethyl)-1H-pyrazole

1.98 g of 3-(Pentafluoropropyl)-1H-pyrazole-1-ylmethanol dissolved in 20 ml of dichloromethane. To the solution was added 1.5 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining a 2.01 g of 1-(chloromethyl)-3-(pentafluoropropyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 5.89 (2H, s), of 6.65 (1H, d), 7,71 (1H, d).

Reference example get 28-1

4-Bromo-3-(pentafluoroethyl)-1H-pyrazole

of 9.30 g of 3-(Pentafluoroethyl)-1H-pyrazole suspended in 90 ml of water and the suspension added 6.0 g of 50% aqueous sodium hydroxide solution. The mixture is cooled to 0°C, then added to the mixture 8,79 g of bromine, followed by stirring at room temperature for 7 hours. The reaction mixture was extracted with ethyl acetate. The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure, thus obtaining 13,72 g of 4-bromo-3-(pentafluoroethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 7,71 (1H, s).

Reference example get 28-2

4-Bromo-3-(pentafluoroethyl)-1H-pyrazole-1-ylmethanol

The mixture 13,72 g of 4-bromo-3-(pentaform the filing)-1H-pyrazole and 3.00 g of paraformaldehyde was stirred at 130°C for 5 hours. After cooling the reaction mixture to room temperature, add acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure. To the filtrate add hexane, resulting in a crystalline substance. Crystalline material is collected, while receiving of 7.69 g of 4-bromo-3-(pentafluoropropyl)-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): of 3.53 (1H, user. C)5,54 (2H, s), 7,73 (1H, s).

Reference example get 28-3

4-Bromo-1-(chloromethyl)-3-(pentafluoroethyl)-1H-pyrazole

of 6.49 g of 4-Bromo-3-(pentafluoropropyl)-1H-pyrazole-1-ylmethanol dissolved in 60 ml of dichloromethane. To the solution was added 3.2 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining at 6.84 g of 4-bromo-1-(chloromethyl)-3-(pentafluoropropyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 5.82 (2H, s), of 7.75 (1H, s).

Reference example get 29-1

4-(Trifluoromethyl)-1H-imidazol-1-ylmethanol

A mixture of 1.80 g of 4-(trifluoromethyl)-1H-imidazole, 0,78 g of paraformaldehyde was stirred at 140°C for 4 hours. After cooling the reaction mixture to room temperature, add acetone. The mixture is filtered and then the filtrate is concentrated under reduced pressure, procapra this 2.16 g of 4-(trifluoromethyl)-1H-imidazol-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): of 5.39 (2H, d), 7,44 (1H, s), to 7.61 (1H, s).

Reference example get 29-2

Hydrochloride of 1-(chloromethyl)-4-(trifluoromethyl)-1H-imidazole

2.16 g of 4-(Trifluoromethyl)-1H-imidazol-1-ylmethanol dissolved in 40 ml of dichloromethane. To the solution was added 1.9 ml of thionyl chloride, followed by stirring the mixture at room temperature over night. The reaction mixture was concentrated under reduced pressure, thus obtaining 2,90 g of the hydrochloride of 1-(chloromethyl)-4-(trifluoromethyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 6,12 (2H, s), 8,10 (1H, s), 8,16 (1H, s).

Reference example obtaining 30-1

3-Cyano-1H-indol-1-ylmethanol

A mixture of 1.42 g of 3-cyano-1H-indole, of 0.60 g of paraformaldehyde and 0.1 g of triethylamine was stirred at 130°C for 1 hour. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1,69 g 3-cyano-1H-indol-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): to 3.73 (1H, user., C)5,64 (2H, d), 7,29-7,39 (2H, m), 7,56-to 7.59 (1H, m), 7,71 to 7.75 (2H, m).

Reference example get 30-2

1-(Chloromethyl)-3-cyano-1H-indol

1,69 g 3-Cyano-1H and the Dol-1-ylmethanol dissolved in 30 ml of dichloromethane. To the solution was added to 1.4 ml of thionyl chloride, followed by stirring the mixture at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, thus obtaining 70 g of 1-(chloromethyl)-3-cyano-1H-indole.

1H-NMR (DMSO-d6, TMS, δ (ppm)): 6,44 (2H, s), 7,34-of 7.48 (2H, m), of 7.64-7,74 (1H, m), 7,83 (1H, d), of 8.47 (1H, s).

Reference example get 31-1

3-Formyl-1H-indole-1-ylmethanol

A mixture of 5.81 g of 3-formyl-1H-indole, of 1.80 g of paraformaldehyde and 0.40 g of triethylamine was stirred at 120°C for 3 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered and then the filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining is 3.08 g of 3-formyl-1H-indole-1-ylmethanol.

1H-NMR (DMSO-d6, TMS, δ (ppm)): 5,61 (2H, d), is 6.78 (1H, t), 7,21-7,34 (2H, m), 7,49 (1H, d), 8,08 (1H, d), a 8.34 (1H, s), 9,94 (1H, s).

Reference example get 31-2

1-(Chloromethyl)-3-formyl-1H-indole

is 3.08 g of 3-formyl-1H-indole-1-ylmethanol dissolved in 60 ml of dichloromethane. To the solution was added 2.5 ml of thionyl chloride, followed by stirring the mixture at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, thus obtaining 3,02 g -(chloromethyl)-3-formyl-1H-indole.

1H-NMR (CDCl3, TMS, δ (ppm)): of 5.99 (2H, s), 7,35-7,52 (3H, m), 7,81 (1H, s), 7,83 (1H, d), 8,32 (1H, d), of 10.05 (1H, s).

Reference example get 32-1

3-(TRIFLUOROACETYL)-1H-indol-1-ylmethanol

The mixture 4,80 g of 3-(TRIFLUOROACETYL)-1H-indole, 1.35 g of paraformaldehyde and 0.10 g of triethylamine was stirred at 130°C for 2 hours. After cooling the reaction mixture to room temperature, to the reaction mixture acetone. The mixture is filtered and then the filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel and to the residue add hexane, the result is a crystalline substance. Crystalline material is collected, while receiving are 5.36 g of 3-(TRIFLUOROACETYL)-1H-indol-1-ylmethanol.

1H-NMR (DMSO-d6, TMS, δ (ppm)): 5,71 (2H, d), 6,92 (1H, t), of 7.36-the 7.43 (2H, m), 7,76 (1H, d), 8,19 (1H, d), 8,31 (1H, s).

Reference example get 32-2

1-(Chloromethyl)-3-(TRIFLUOROACETYL)-1H-indole

are 5.36 g of 3-(TRIFLUOROACETYL)-1H-indol-1-ylmethanol dissolved in 60 ml of dichloromethane. To the solution was added 2.5 ml of thionyl chloride, followed by stirring the mixture at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure and the residue is recrystallized from a mixture of hexane-chloroform, while receiving 3,79 g of 1-(chloromethyl)-3-(Tr is peracetyl)-1H-indole.

1H-NMR (CDCl3, TMS, δ (ppm)): 6,00 (2H, s), 7,30-EUR 7.57 (3H, m), with 8.05 (1H, s), 8,39-to 8.41 (1H, m).

Reference example receive 33-1

2-(4-Methoxybenzyl)-4-thiocyanato-2H-pyrazole-3-ylamine

the 3.89 g of potassium Thiocyanate are suspended in 40 ml of methanol. In the atmosphere of nitrogen, the suspension is cooled to -78°C. to 1.76 g of bromine, dissolved in 40 ml of methanol, is added dropwise to the suspension over a period of 30 minutes, followed by stirring for 30 minutes. Then thereto is added dropwise within 10 minutes add 2,03 g of 2-(4-methoxybenzyl)-2H-pyrazole-3-ylamine, which is dissolved in 10 ml of methanol, followed by stirring at -78°C for 1 hour and at room temperature for 8 hours. The reaction mixture was concentrated under reduced pressure. To the residue water is added and the mixture extracted with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate and then concentrated. The residue is subjected to column chromatography on silica gel, thus obtaining 1.54 g of 2-(4-methoxybenzyl)-4-thiocyanato-2H-pyrazole-3-ylamine.

1H-NMR (DMSO-d6, TMS, δ (ppm)): and 3.72 (3H, s), 5,07 (2H, s), 6,37 (2H, user. C)6,87 (2H, d), 7,14 (2H, d), 7,42 (1H, s).

Reference example get 33-2

4-{[5-Amino-1-(4-methoxybenzyl)-1H-pyrazole-4-yl]ditio}-1-(4-methoxybenzyl)-1H-pyrazole-5-amine

1.42 g of 2-(4-Methoxybenzyl)-4-t is oceanto-2H-pyrazole-3-ylamine added to 20 ml of 10% aqueous sodium hydroxide solution and the mixture is then refluxed for 2 hours. The reaction mixture is cooled to room temperature, resulting in a crystalline substance. Crystalline material is collected by filtration. The crystals are washed with 30 ml of water three times. The crystals are dried under reduced pressure, to thereby obtain 1.27 g of 4-{[5-amino-1-(4-methoxybenzyl)-1H-pyrazole-4-yl]ditio}-1-(4-methoxybenzyl)-1H-pyrazole-5-amine.

1H-NMR (DMSO-d6, TMS, δ (ppm)): 3,71 (6N, (C), 5,07 (4H, s), 5,73 (4H, user. C)6,83 (4H, d), 6,98 (2H, s), 7,07 (4H, d).

Reference example get 33-3

4-{[Dichloromethyl]thio}-1-(4-methoxybenzyl)-1H-pyrazole-5-amine

1,58 g of 4-{[5-Amino-1-(4-methoxybenzyl)-1H-pyrazole-4-yl]ditio}-1-(4-methoxybenzyl)-1H-pyrazole-5-amine was dissolved in 20 ml of N,N-dimethylformamide. To the solution under ice cooling, add 20 ml of water, 1.42 g of sodium bicarbonate and 2.93 g of hydrosulfite sodium. To this mixture 5,28 g trichloromethane, followed by stirring at room temperature for 15 hours. To the reaction mixture, water is added and the mixture extracted with ethyl acetate. The organic layer is washed with water, dried over sodium sulfate and filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 1.04 g of 4-{[dichloromethyl]thio}-1-(4-methoxybenzyl)-1H-pyrazole-5-amine.

1H-NMR (CDCl3, TMS, δ ppm)): with 3.79 (3H, C)to 3.99 (2H, user. C)5,16 (2H, s)6,86 (2H, d), 7,11 (2H, d), 7,52 (1H, s).

Reference example get 33-4

4-{[Dichloromethyl]thio}-1-(4-methoxybenzyl)-1H-pyrazole

1.04 g of 4-{[Dichloromethyl]thio}-1-(4-methoxybenzyl)-1H-pyrazole-5-amine was dissolved in 20 ml of tetrahydrofuran. To the solution was added 1.55 g of tert-butylnitrite followed by boiling the mixture under reflux for 3 hours. After cooling the reaction mixture to room temperature, to the reaction mixture, water is added and the mixture extracted with diethyl ether. The organic layer is washed with water, dried over sodium sulfate and filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,94 g of 4-{[dichloromethyl]thio}-1-(4-methoxybenzyl)-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 3,81 (3H, s), at 5.27 (2H, s), 6.89 in (2H, d), 7,19 (2H, d), 7,60 (1H, s), 7,72 (1H, s).

Reference example get 33-5

4-{[Dichloromethyl]thio}-1H-pyrazole

4-{[Dichloromethyl]thio}-1-(4-methoxybenzyl)-1H-pyrazole are dissolved in 6 ml triperoxonane acid, followed by stirring the solution at 65°C for 3 hours. After cooling the reaction mixture to room temperature there was added a saturated aqueous solution of sodium bicarbonate. The mixture extragear the Ute with ethyl acetate. The organic layer is dried over anhydrous sodium sulfate and filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,19 g of 4-{[dichloromethyl]thio}-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 7,88 (2H, s).

Reference example get 33-6

4-{[Dichloromethyl]thio}-1H-pyrazole-1-ylmethanol

to 0.19 g of 4-{[Dichloromethyl]thio}-1H-pyrazole are dissolved in 5 ml of tetrahydrofuran. To the solution add 5 ml of 36% formaldehyde in water and 0.1 ml of 10% tetrabutylammonium hydroxide in water, followed by stirring at room temperature for 4 hours. To the reaction mixture, water is added and the mixture extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 0,22 g 4-{[dichloromethyl]thio}-1H-pyrazole-1-ylmethanol.

1H-NMR (CDCl3, TMS, δ (ppm)): to 5.57 (2H, s), to 7.77 (1H, s), of 7.90 (1H, s).

Reference example get 33-7

1-(Chloromethyl)-4-{[dichlorofluoromethyl)thio}-1H-pyrazole

0,22 g 4-{[Dichloromethyl]thio}-1H-pyrazole-1-ylmethanol dissolved in 10 ml of chloroform. To the solution was added 0.3 ml of thionyl chloride and the mixture is boiling the under reflux for 4 hours. The reaction mixture was concentrated under reduced pressure, thus obtaining 0.21 g of 1-(chloromethyl)-4-{[dichlorofluoromethyl)thio}-1H-pyrazole.

1H-NMR (CDCl3, TMS, δ (ppm)): 5,88 (2H, s), 7,79 (1H, s), 7,92 (1H, s).

Reference example get 34-1

3-{[Dichloromethyl]thio}-1H-indol-1-ylmethanol

0.50 g of 3-{[Dichloromethyl]thio}-1H-indole are dissolved in 10 ml of tetrahydrofuran. To the solution add 10 ml of 36% formaldehyde in water and 0.4 ml of 10% tetrabutylammonium hydroxide in water, followed by stirring the mixture at room temperature for 30 minutes. To the reaction mixture, water is added and the mixture extracted with MTBE. The organic layer is washed with water, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, thus obtaining of 0.54 g of 3-{[dichloromethyl]thio}-1H-indol-1-ylmethanol.

1H-NMR (DMSO-d6, TMS, δ (ppm)): 5,61 (2H, d), of 6.73 (1H, t), 7.23 percent-7,33 (2H, m), 7,66-of 7.70 (2H, m), of 8.04 (1H, s).

Reference example get 34-2

1-(Chloromethyl)-3-{[dichloromethyl]thio}-1H-indole

of 0.54 g of 3-{[Dichloromethyl]thio}-1H-indol-1-ylmethanol dissolved in 10 ml of chloroform. To the solution was added 0.3 ml of thionyl chloride and the mixture is refluxed for 4 hours. The reaction mixture was concentrated under reduced pressure, thus obtaining 0,61 g 1(x is ormetal)-3-{[dichloromethyl]thio}-1H-indole.

Reference example get 35

1-Chloromethyl-3-nitro-1H-pyrrol

Blend 840 mg of 3-nitro-1H-pyrrole, 15 ml of tetrahydrofuran and 15 ml of 36% formaldehyde in water. At room temperature, add 0.5 ml of 10% tetrabutylammonium hydroxide in water, followed by stirring the mixture at room temperature for 30 minutes. The reaction mixture was poured into a mixture of ice-water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, thus obtaining 1-hydroxymethyl-3-nitro-1H-pyrrole.

The obtained 1-hydroxymethyl-3-nitro-1H-pyrrole dissolved in 3 ml of chloroform and to the solution add 3 ml of thionyl chloride, followed by stirring the solution at room temperature for 1 hour. After cooling the reaction mixture to 0°C. it is poured into a mixture of ice-water. The mixture is extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel, thus obtaining 620 mg of 1-chloromethyl-3-nitro-1H-pyrrole.

1H-NMR (CDCl3, TMS, δ (ppm)): 5,63 (2H, s), 6,77-of 6.78 (2H, m), 7,8-of 7.69 (1H, m).

Reference example get 36

1-Chloromethyl-3-cyano-4-trifluoromethyl-1H-pyrrol

Mix 585 mg of 3-cyano-4-trifluoromethyl-1H-pyrrole, 10 ml of tetrahydrofuran and 10 ml of 36% formaldehyde in water. To the mixture at room temperature, add 0.1 ml of 10% tetrabutylammonium hydroxide in water, followed by stirring the mixture at room temperature for 30 minutes. The reaction mixture was poured into a mixture of ice-water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, thus obtaining 1-hydroxymethyl-3-cyano-4-trifluoromethyl-1H-pyrrole.

The obtained 1-hydroxymethyl-3-cyano-4-trifluoromethyl-1H-pyrrole dissolved in 3 ml of chloroform and add 3 ml of thionyl chloride, followed by stirring the mixture at room temperature for 1 hour. After cooling the reaction mixture to 0°C. it is poured into a mixture of ice-water. The mixture is extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, while receiving 800 mg of 1-chloromethyl-3-cyano-4-trifluoromethyl-1H-pyrrole.

1H-NMR (CDCl3, TMS, δ (ppm)): 5,62 (2H, s), 7,2 (1H, d), 7,39 (1H, d).

Reference example receiving 37

1-Chloromethyl-4-trifluoromethyl-3-etoxycarbonyl-1H-pyrrol

Mix 207 mg of 4-trifluoromethyl-3-etoxycarbonyl-1H-pyrrole, 5 ml of tetrahydrofuran and 5 ml of 36% formaldehyde in water. To the mixture at room temperature, add 0.2 ml of 10% tetrabutylammonium hydroxide in water, followed by stirring at room temperature for 10 minutes. The reaction mixture was poured into a mixture of ice-water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, thus obtaining the crude product, 1-hydroxymethyl-4-trifluoromethyl-3-etoxycarbonyl-1H-pyrrole.

The obtained 1-hydroxymethyl-4-trifluoromethyl-3-etoxycarbonyl-1H-pyrrole dissolved in 3 ml of chloroform and add 4 ml of thionyl chloride, followed by boiling under reflux for 30 minutes. After cooling the reaction mixture to 0°C. it is poured into a mixture of ice-water. The mixture is extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, while receiving 225 mg of 1-chloromethyl-4-trifluoromethyl-3-etoxycarbonyl-1H-Pierre is La.

1H-NMR (CDCl3, TMS, δ (ppm)): to 1.35 (3H, t), or 4.31 (2H, square), 5,64 (2H, s), 7,17 (1H, d), 7,51 (1H, d).

Reference example get 38

1-Chloromethyl-3-cyano-1H-pyrrol

Mix 670 mg of 3-cyano-1H-pyrrol 10 ml tetrahydrofuran and 10 ml of 36% formaldehyde in water. At room temperature, add 0.1 ml of 10% tetrabutylammonium hydroxide in water, followed by stirring the mixture at room temperature for 30 minutes. The reaction mixture was poured into a mixture of ice-water and the total mixture is extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, thus obtaining 1-hydroxymethyl-3-cyano-1H-pyrrole.

The obtained 1-hydroxymethyl-3-cyano-1H-pyrrole dissolved in 3 ml of chloroform, add 2 ml of thionyl chloride, followed by stirring the mixture at room temperature for 1 hour. After cooling the reaction mixture to 0°C. it is poured into a mixture of ice-water. The mixture is extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure and subjected to column chromatography on silica gel, thus obtaining 290 mg of 1-chloromethyl-3-tzia is about-1H-pyrrole.

1H-NMR (CDCl3, TMS, δ (ppm)): to 5.66 (2H, s), 6,46-6,47 (1H, m), at 6.84 (1H, d), 7,32-7,33 (1H, m).

Examples of the drugs listed below. In addition, "part" refers to the mass portion. Compounds of the present invention indicate their numbers specified above.

Example 1 preparation

9 parts of each of compounds (1) to (48) of the present invention is dissolved in a 37.5 parts of xylene and 37.5 parts of dimethylformamide and to the solution was added 10 parts polyoxyethyleneglycol simple ether and 6 parts of dodecylbenzenesulfonate calcium, followed by stirring and thorough mixing, while receiving emulsifiable concentrate of each compound.

Example 2 preparation

To 40 parts of each of compounds (1) to (48) of the present invention added 5 parts of SORPOL 5060 (registered trade name of TOHO DEPENDING KOGYO) with subsequent good stirring of the mixture. To a mixture of 32 parts of CARPLEX #80 (registered trade name of SHIONOGI & Co., fine powder of synthetic hydrated silicon oxide) and 23 parts of diatomaceous earth 300 mesh, followed by stirring the mixture with the electric mixer, while receiving wettable powder for each compound.

Example 3 preparation

To 3 parts of each of compounds (1) to (48) of the present invention add 5 parts of finely smallchange powder of synthetic hydrated silicon oxide, 5 parts of dodecylbenzenesulfonate sodium, 30 parts of bentonite and 57 parts of clay, followed by good mixing and blending. Then to this mixture is added a suitable amount of water followed by additional mixing, granulating the granulator and air drying the mixture, thus obtaining pellets of each connection.

Example 4 drug

4.5 parts of each of compounds (1) to (48) of the present invention, 1 part of fine powder of synthetic hydrated silica, 1 part Doriresu In (Sankyo Co., Ltd.) as a occulant and 7 parts of clay are well mixed in a mortar, followed by stirring and mixing with the electric mixer. To the resulting mixture add 86,5 part Komkova clay with subsequent good stirring and mixing the mixture, thus obtaining the dust of each compound.

Example 5 drug

10 parts of each of compounds (1) to (48) of the present invention, 35 parts of white carbon, containing 50 parts of ammonium salt of sulfate polyoxyethyleneglycol simple ether and 55 parts of water are mixed and pulverized by a wet grinding method, while receiving the drug every connection.

Example 6 preparation

0.5 parts of each of compounds (1) to (48) of the present invention is dissolved in 10 parts of dichloromethane and education is asisa solution is mixed with 89,5 part of Iso-Par M (isoparaffin, registered trade name of EXXON CHEMICAL LTD), while receiving oil solution.

Example 7 preparation

0.1 part of each of compounds (1) to (48) of the present invention and 49.9 parts of the NEO-CHIOZOL (CHUO KASEI Co., LTD) is loaded into the container for the aerosol and on the cylinder is fixed aerosol valve. Then the cylinder is placed 25 parts of dimethyl simple ether and 25 parts of LPG, followed by shaking the container and install it starter with obtaining thus an oil aerosol.

Example 8 preparation

of 0.6 parts of each of compounds (1) to (48) of the present invention, 0.01 part of BHT, 5 parts of xylene, 3,39 parts of deodorized kerosene and 1 part of emulsifier [Atmos 300 (registered trade name for ATMOS CHEMICAL LTD)] are mixed and dissolved. The resulting solution and 50 parts of distilled water are loaded into the aerosol container and the container is fixed valve. 40 parts of a propellant (LPG) download under pressure through the valve, thus obtaining a water spray.

The following example tests demonstrates that the compound of the present invention has pesticidal activity and can be used as the active ingredient of the composition for pest control. Compounds of the present invention indicate their numbers specified above.

The test example 1

The prep is at, obtained according to example 5 preparation with the use of compounds of the present invention(2), (3), (4), (5), (6), (7), (8), (9), (11), (12), (13), (14), (15), (16), (18), (20), (21), (22), (26), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37), (38), (39), (45) and (48) respectively, was diluted with water so that the concentration of the active ingredient was 500 ppm, thus obtaining the pesticide solution for testing.

Fifty grams molded Bonsoru 2 (manufactured by Sumitomo Chemical Co., Ltd) were placed in a plastic Cup and plastic Cup were sown 10-15 rice seeds. Then the rice plants were grown until the development of the second leaf and then cut in the cuttings of the same height 5 see Pesticide solution for testing, obtained above, was sprayed at the rate of 20 ml/Cup on these rice plants. After the pesticide solution sprayed on the rice plants was dried, they were placed in a plastic Cup, then thirty larvae of Nilaparvata lugens first stages of development were placed free on the rice plants with subsequent coating of a plastic Cup with a lid in order to test the pests did not run away. Then the plastic Cup was left in a greenhouse (25°C). On the sixth day after the release of larvae of Nilaparvata lugens were counting the number of parasitic Nilaparvata lugens on rice plants.

As a result of processing each of the compounds of the present invention(2), (3), (4), (5), (6), (7), (8), (9),(11), (12), (13), (14), (15), (16), (18), (20), (21), (22), (26), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37), (38), (39), (45) and (48) the number of parasitic Nilaparvata lugens was no more than 3.

The test example 2

The preparation obtained according to example of the preparation 5 using the compounds of the present invention(2), (4), (6), (8), (9), (11), (12), (13), (15), (18), (21), (22), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37), (38), (44), (46) and (47) respectively, was diluted with water so that the concentration of the active ingredient was 500 ppm, thus obtaining the pesticide solution for testing.

Plastic Cup seeded cucumber plants were grown until the development of the first true leaf, approximately twenty Aphis gossypii were given the opportunity to develop as parasites on plants. The next day on cucumber plants were sprayed to the above solution for testing with a consumption rate of 20 ml/Cup. On the sixth day after the application was calculated the number of Aphis gossypii.

As a result, the processing of each of the compounds of the present invention(2), (4), (6), (8), (9), (11), (12), (13), (15), (18), (21), (22), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37), (38), (44), (46) and (47) the number of parasitic insects was not more than 3.

The test example 3

The product obtained according to the example of the drug 5

the use of compounds of the present invention(2), (3), (4), (6), (7), (8), (11), (12), (13), (15), (16), (19), (20), (21), (22), (28), (29), (30), (31), (32), (33), (34), (36), (37), (38) and (39) with the responsibility was diluted with water so that the concentration of the active ingredient was 500 ppm, thus obtaining the pesticide solution for testing.

At the bottom of a polyethylene Cup having a diameter of 5.5 cm, was placed a filter paper having the same diameter, and filter paper was added dropwise 0.7 ml of the above pesticide solution for testing and then moved to her evenly 30 mg of sucrose as bait. Ten female Musca domestica adult stage were placed in the loose way in a polyethylene Cup and the Cup was covered with a lid. After 24 hours counted the number of surviving and dead Musca domestica and calculated the percentage of dead insects.

As a result, the processing of each of the compounds of the present invention(2), (3), (4), (6), (7), (8), (11), (12), (13), (15), (16), (19), (20), (21), (22), (28), (29), (30), (31), (32), (33), (34), (36), (37), (38) (39) the percentage of dead insects was 90% or more.

The test example 4

The preparation obtained according to example of the preparation 5 using the compounds of the present invention(2), (3), (4), (6), (7), (8), (9), (11), (12), (13), (15), (16), (18), (19), (20), (21), (22), (27), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37), (38) and (43) respectively, was diluted with water so that the concentration of the active ingredient was 500 ppm, thus obtaining the pesticide solution for testing.

At the bottom of a polyethylene Cup having a diameter of 5.5 cm, POM who attended filter paper having the same diameter, and filter paper was added dropwise 0.7 ml of the above pesticide solution for testing and then moved to her evenly 30 mg of sucrose as bait. Two male Blattella germanica adult stage were placed in the loose way in a polyethylene Cup and the Cup was covered with a lid. After 6 days was counted the number of surviving and dead Blattella germanica and calculated the percentage of dead insects.

As a result, the processing of each of the compounds of the present invention(2), (3), (4), (6), (7), (8), (9), (11), (12), (13), (15), (16), (18), (19), (20), (21), (22), (27), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37), (38) and (43) the percentage of dead insects was 100%.

The test example 5

The preparation obtained according to example of the preparation 5 using the compounds of the present invention(1), (2), (3), (4), (5), (6), (7), (8), (9), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (20), (21), (22), (23), (25), (27), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37), (38), (39), (41), (44), (45), (46), (47) and (48) respectively, was diluted with water so that the concentration of the active ingredient was 500 ppm, so the way the pesticide solution for testing.

0.7 ml of the above pesticide solution to be tested was added to 100 ml of water, passed through an ion exchanger (concentration of active ingredient: 3,5 ppm). Twenty larvae of Culex pipiens pallens last stages were placed in the solution. SPU is thee one day counted the number of surviving and dead Culex pipiens pallens and calculated the percentage of dead pests.

As a result, the processing of each of the compounds of the present invention(1), (2), (3), (4), (5), (6), (7), (8), (9), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (20), (21), (22), (23), (25), (27), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37), (38), (39), (41), (44), (45), (46), (47) and (48) the percentage of dead pests was not less than 95%.

INDUSTRIAL APPLICABILITY

Compounds of the present invention have excellent activity against pests and are applicable as the active ingredient of the pesticide.

1. Derived malononitrile represented by the formula (I):

where in the formula, R1represents a hydrogen atom;
R2represents a hydrogen atom;
R3represents a hydrogen atom;
R4represents a C1-C5is an alkyl group substituted by at least one halogen atom, With2-C5-alkenylphenol group;
R5represents a hydrogen atom, a halogen atom, a C1-C5is an alkyl group;
at least one of the values X1X2and X3represents CR6and other means nitrogen atoms;
R6represents a hydrogen atom, a halogen atom, a cyano, a nitro-group, formyl group1-C5is an alkyl group, optionally substituted by at least one halogen atom, With1 -C5-allylthiourea, substituted by at least one halogen atom, With2-C6-alkylcarboxylic group, substituted by at least one halogen atom, With2-C5-alkoxycarbonyl group, or a group (CH2)mQ, where m=0, and Q means phenyl; and
when one of R5and R6associated with two atoms in adjacent positions, or two R6associated with two atoms in adjacent positions they may be connected with each other in extreme positions with education2-C6-alkadienes group, or With4-C6-allendales group.

2. Derived malononitrile according to claim 1, which is represented by formula (I-1):

where in the formula, R1, R2, R3and R4have the same meanings as described in claim 1;
R5represents a hydrogen atom, halogen atom, or With1-C5is an alkyl group;
R6-1represents a hydrogen atom, halogen atom, or With1-C5is an alkyl group, optionally substituted by at least one halogen atom.

3. Derived malononitrile according to claim 1, which is represented by formula (I-2):

where in the formula, R1, R2, R3and R4have the same meanings as described in claim 1;
R5represents a hydrogen atom;
what each of R 6-1and R6-2represents a hydrogen atom, a C1-C5is an alkyl group substituted by at least one halogen atom.

4. Derived malononitrile according to claim 1, which is represented by formula (I-3):

where in the formula
R1, R2, R3and R4have the same meanings as described in claim 1;
R5represents a hydrogen atom, a halogen atom or With1-C5is an alkyl group;
each of R6-1and R6-2represents a hydrogen atom, a halogen atom, a cyano, a nitro-group, formyl group1-C5is an alkyl group, optionally substituted by at least one halogen atom, With1-C5-allylthiourea, substituted by at least one halogen atom, With2-C6-alkylcarboxylic group, substituted by at least one halogen atom, With2-C5-alkoxycarbonyl group, or phenyl group.

5. Derived malononitrile according to claim 1, which is represented by formula (I-4):

where in the formula
R1, R2, R3and R4have the same meanings as described in claim 1;
R5represents a hydrogen atom, halogen atom, or With1-C5is an alkyl group;
each of R6-1and R6-2represents a hydrogen atom, the atom Galaga is a, a cyano, a nitro-group, formyl group1-C5is an alkyl group, optionally substituted by at least one halogen atom, With1-C5-allylthiourea, substituted by at least one halogen atom, With2-C6-alkylcarboxylic group, substituted by at least one halogen atom, With2-C5-alkoxycarbonyl group.

6. Derived malononitrile on any of PP-5, where
R5represents a hydrogen atom;
each of R6-1and R6-2represents a hydrogen atom, a halogen atom, a C1-C5is an alkyl group, optionally substituted by at least one halogen atom, or With1-C5-allylthiourea, substituted by at least one halogen atom.

7. Derived malononitrile on any of PP-5, where
R1, R2, R3and R5represent hydrogen atoms;
R4represents a C1-C5is an alkyl group substituted by at least one halogen atom, or With2-C5-alkenylphenol group;
each of R6-1and R6-2represents a hydrogen atom, a halogen atom, a C1-C5is an alkyl group, optionally substituted by at least one halogen atom, or With1-C5-allylthiourea, substituted, at least one at the PTO halogen.

8. Derived malononitrile according to any one of claim 2 to 5, where
R1, R2, R3and R5represent hydrogen atoms;
R4represents a 2,2,2-triptorelin group or vinyl group;
each of R6-1and R6-2represents a hydrogen atom, a halogen atom, a C1-C5is an alkyl group, optionally substituted by at least one halogen atom, or With1-C5-allylthiourea, substituted by at least one halogen atom.

9. Composition for combating insects comprising an effective amount of a derivative malononitrile according to claim 1 and a carrier.

10. A method of combating pests comprising applying an effective amount of a derivative malononitrile according to claim 1 to pests or their habitat.

11. The application of the derived malononitrile according to claim 1 as an agent for pest control.



 

Same patents:

FIELD: pharmacology.

SUBSTANCE: described are novel derivatives of triazole of general formulas (I) or (II) or their pharmaceutically acceptable salts, where R1 represents H, C1-C6-alkyl, or group CONRaRb, Ra represents hydrogen or C1-C6-alkyl; R2 represents H or C1-C6-alkyl; R3 represents H or F, CI, Br or I; R4 represents H; R5 represents CF3 or O-(C1-C4)alkyl, three times substituted with F; R6 and R7 each independently represents H, F or CF3, on condition that one of R6 and R7 always represents H.

EFFECT: application of said compounds for preparing medication for treatment and prevention of pain or pain-induced disturbances; pharmaceutical composition containing novel compounds, and method of their obtaining.

9 cl, 20 ex

FIELD: chemistry.

SUBSTANCE: invention claims substituted O-[ω-(azol-1-yl)alkyl]-N-phenylthiocarbamates of formula I: where Z=CH, N, R=H, Alk, AlkO, Hal etc., m=1, 2, 3, n=0-5, obtained by acylation of ω-(azol-1-yl)alkanols of formula II by substituted phenylisothiocyanates in polar aprotonic solvents in the presence if tertiary amines. Invention allows for more efficient suppression of phytopathogenic fungi in vitro than by such reference material as triadimefon, due to application of fungicide composition including substituted O-[ω-(azol-1-yl)alkyl]-phenylthiocarbamates I, such as O-(imidazole-1-ylmethyl)-N-(2-methyl-phenyl)thiocarbamates.

EFFECT: efficient suppression of phytopatogenic fungi growth.

4 cl, 5 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: in substituted N-[ω-azol-1-yl)alkyl]benzolsulfamides , X and Y represent CH-group, n stands for 2 or 4, R - similar or different stand for alkyl group with number of carbon atoms from 1 to 4, perfluoralkyl group with number of carbon atoms from 1 to 4, perfluoralkoxy group with number of carbon atoms from 1 to 4, nitro group, alkoxycarbonyl group with number of carbon atoms from 1 to 4, and their salts, n stands for 3, R - similar or different stand for alkyl group with number of carbon atoms from 2 to 4, perfluoralkyl group with number of carbon atoms from 1 to 4, perfluoralkoxy group with number of carbon atoms from 2 to 4, alkoxycarbonyl group with number of carbon atoms from 1 to 4, and their salts, where X stands for CH-group, Y stands for nitrogen atom, n stands for 2, R - similar or different stand for alkyl group with number of carbon atoms from 2 to 4, perfluoralkyl group with number of carbon atoms from 1 to 4, perfluoralkoxy group with number of carbon atoms from 1 to 4, nitro group, alkoxycarbonyl group with number of carbon atoms from 1 to 4, and their salts, n stands for 3 or 4, R - similar or different stand for alkyl group with number of carbon atoms from 1 to 4, perfluoralkyl group with number of carbon atoms from 1 to 4, perfluoralkoxy group with number of carbon atoms from 1 to 4, nitro group, alkoxycarbonyl group with number of carbon atoms from 1 to 4, and their salts, where X and Y simultaneously are chain C-CH=CH-CH=CH-C constituting together annelated with heterocycle ring, n stands for whole number from 2 to 4, R - similar or different stand for alkyl group with number of carbon atoms from 1 to 4, perfluoralkyl group with number of carbon atoms from 1 to 4, perfluoralkoxy group with number of carbon atoms from 1 to 4, nitro group, alkoxycarbonyl group with number of carbon atoms from 1 to 4, and their salts, methods of their obtaining and application as anti-aggregation preparations. Anti-aggregation activity of N-[ω -azol-1-yl)alkyl]benzolsulfamides, of general formula I, for instance, hydrochloride of N-[4-(1H-triasol-1-yl)butyl]-n-methylbenzolsulfumide (35) is higher than of etalon dazoxyben.

EFFECT: increase of anti-aggregation activity.

4 cl, 5 tbl, 5 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to substituted ω-azolylalkane anilides. Invention describes substituted ω-(1H-azol-1-yl)-N-phenylalkaneamides of the general formula (I): wherein Z and Y mean nitrogen atom of CH-group, or they represent the chain -C-CH=CH-CH=CH-C- simultaneously and forming in common an anellated ring; n means a whole number from 1 to 3; Rm are similar or different and mean hydrogen, halogen atom, alkyl group with number of carbon atoms from 1 to 4, alkoxy group, alkylenedioxy group, benzyloxy group, perfluoroalkyl group with number of carbon atoms from 1 to 4, nitro group, alkoxycarbonyl group, carboxyl group, halogenphenylthio group, halogenbenzoyl group; m means a whole number from 0 to 5, their salts with acids. Also, invention describes methods for synthesis of compounds of the formula (I) and their using as anti-aggregative preparations. Invention provides synthesis of novel compounds possessing the useful biological properties.

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

8 tbl, 11 ex

FIELD: organic chemistry, chemical technology.

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EFFECT: improved method of synthesis.

5 cl, 17 ex

FIELD: organic chemistry, fungicides.

SUBSTANCE: invention describes substituted 1-(pyridinyl-2)-2-azolylethanols of the general formula (I): wherein R means hydrogen atom, direct or branched alkyl with 1 to 8 carbon atoms, cycloalkyl with from 3 to 8 carbon atoms; X means nitrogen atom or CH-group. Also, invention relates to a method for synthesis of these compounds and a fungicide composition that contains compound of the formula (I). Invention provides expanding assortment of fungicides for carrying out the effective control of harmful fungi.

EFFECT: valuable fungicide properties of compounds and composition.

5 cl, 1 tbl, 7 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel α-(N-sulfonamido)acetamides of the formula (I) or their optical isomers wherein values R1, R, R2 and R3 are given in the invention claim. Proposed compounds are inhibitors of production of β-amyloid peptide and can be used for inhibition of production of β-amyloid peptide. Also, invention relates to pharmaceutical composition based on these compounds and to a method for inhibition of production of β-amyloid peptide.

EFFECT: valuable medicinal property of compounds and pharmaceutical composition.

22 cl, 23 sch, 4 tbl, 501 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes a novel triazole derivative of the general formula (I): wherein R1 represents phenyl group optionally substituted with one or two groups chosen from (C1-C6)-alkyl group, (C1-C6)-halogenalkyl group, (C1-C6)-alkoxy-group, (C1-C6)-halogenalkoxy-group, halogen atom, nitro-group or cyano-group, styrenyl group, (C1-C6)-alkoxystyrenyl-group or pyridyl group; R2 represents methyl or amino-group; A and B are carbon atoms; C and D represent independently carbon or nitrogen atom, and its nontoxic salt and pharmaceutical composition based on thereof. Also, invention relates to methods for synthesis of novel compounds, novel intermediate substances of the formula: wherein R2, A, B, C and D have above given values; n means a whole number from 0 to 2, and to a method for their synthesis. Compounds of the formula (I) possess anti-inflammatory activity and can be used potentially in treatment of fever, pain and inflammation.

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

9 cl, 2 tbl, 50 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to derivatives of adamantine, in particular, to a new method for preparing adamant-1-yl-containing azoles of the general formula I-VIII: wherein R1 means ; R2 means ; R3 means ; R4 means ; R5 means ; R6 means ; R7 means , and R8 means . Indicated derivatives of adamantine are semifinished products used in synthesis of biologically active substances. Proposed method for preparing these compounds involves using a new method for synthesis of adamant-1-yl-containing azoles that includes the addition reaction of azoles: 2-methylimidazole, 3(5)-methylpyrazole and 4-methylpyrazole, 3,4-dinitropyrazole, 1,2,4-triazole, 3-methylpyrazole, 3-nitro-1,2,4-triazole and 5-methyltetrazole to 1,3-dehydroadamantane in the mole ratio of 1,3-dehydroadamantane to azole = 1:1 in diethyl ether medium at temperature 100°C for 4-5 h.

EFFECT: improved preparing method.

8 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to water-soluble azole compounds that can be used in biology and medicine. Invention describes a water-soluble azole compound of the formula (I):

or its pharmaceutically acceptable salt wherein each R and R1 means independently hydrogen atom or (C1-C6)-alkyl; A means group of the formula:

wherein R3 represents phenyl group with one or more halide atoms as substitutes; R4 represents hydrogen atom or -CH3; R5 represents hydrogen atom or in common with R4 it can represent =CH2; R6 represents 5- or 6-membered nitrogen-containing cycle that can comprise if necessary as substituted one or more groups taken among halogen atom, =O group, phenyl substituted with one or more groups taken among -CN, -(C6H4)-OCH2-CF2-CHF2 and -CH=CH-(C6H4)-OCH2-CF2-CHF2 or phenyl substituted with one or more groups taken among halogen atom and methylpyrazolyl group. Also, invention describes a method for preparing a water-soluble azole compound. Invention provides preparing new compounds that can be useful in medicine.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

4 ex

The invention relates to new imidazole derivative of the formula (I):where R1represents phenyl or pyridinyl, substituted by substituents selected from the group comprising (1) phenyl, (2) furyl, thienyl, (3) halogen, (4) halogen(lower)alkyl, (5) lower alkylthio, (6) nitro, (7) lower alkenyl, optionally substituted phenyl, (8) lower quinil, optionally substituted phenyl, (9) lower alkoxy, optionally substituted cyclo(lower)alkyl or phenyl, (10) lower alkyl, optionally substituted, phenyloxy or (11) amino, optionally substituted protected carboxyla; R2represents lower alkyl; R3represents halogen or lower alkyl; R4represents (1) lower alkenyl, optionally substituted phenyl, (2) phenyl, optionally substituted lower alkyl or lower alkenyl, (3) lower alkyl or (4) thienyl, optionally substituted with halogen; a represents a lower alkylene and L represents a simple bond, a lower albaniles or lower alkylene, optionally substituted phenyl or pyridinyl, or-X-CH2- where X represents O or NR5where R5represents hydrogen or n is

The invention relates to a new 2-{4-[4-(4,5-dichloro-2-Mei-1-yl)butyl]-1-piperazinil}-5-torpedinidae formula I (see

The invention relates to compounds of dehalogenation, insecticide/acaricidal agents containing these compounds as active ingredients and intermediates for their production

The invention relates to a new process for the preparation of 2-substituted 5-chloroimidazo-4-carbaldehyde General formula I

< / BR>
where

R denotes hydrogen, alkyl group, alkenylphenol group, cycloalkyl group, benzyl group, phenyl group or aryl group

The invention relates to methods of producing 2-substituted 5-chloroimidazo-4-carbaldehyde General formula 1

< / BR>
These connections form a valuable intermediate products for the manufacture of medicines that lower blood pressure, and compounds with herbicide action

The invention relates to new derivatives of 1-ellimination, to the way they are received, to insecticidenematicides compositions and to a method of combating agricultural pests, particularly ticks, with the soil or damaging the foliage insects and nematodes

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with general formula (I) , where R1 and R2 are independently chosen from hydrogen, halogen, nitro, alkyl, alkylaryl and XYR5; X and Y are independently chosen from O and (CR6R7)n; R3 represents hydrogen, alkyl or M; M represents an ion, chosen from aluminium, calcium, lithium, magnesium, potassium, sodium, zinc or their mixture; Z represents CR4; R4 is chosen from hydrogen, halogen, alkyl, alkylaryl and XYR5; R5 is chosen from aryl, substituted aryl, heteroaryl and substituted heteroaryl; R6 and R7 are independently chosen from hydrogen and alkyl; n is an integer from 1 to 6; at least one of R1 and R2 represents XYR5, and at least one of X and Y represents (CR6R7)n. The invention also pertains to the method of increasing concentration of D-serine and/or reducing concentration of toxic products of D-serine oxidation under the effect of DAAO in mammals, involving introduction into a subject of a therapeutically effective amount of a formula I compound, to the method of treating schizophrenia, treating or preventing loss of memory and/or cognitive ability, to the method of improving learning ability, method of treating neuropathic pain, as well as to a pharmaceutical composition, with DAAO inhibitory activity, based on these compounds.

EFFECT: obtained are new compounds and a pharmaceutical composition based on these compounds.

27 cl, 4 tbl, 72 ex

FIELD: chemistry.

SUBSTANCE: invention can be applied in medicine and concerns inhibitors of MaR-kinase p38 of formula where W represents N or O, when Y represents C, and W represents C, when Y represents N; U represents CH or N; V represents C-E or N; X represents O, S, SO, SO2, NH, C=O,-C=NOR1 or CHOR1; B represents H or NH2; R1, E and A stands for H or various alkyl, heteroalkyl, aromatic and heteroaromatic substitutes.

EFFECT: production of new biologically active compounds.

48 cl, 138 ex, 54 dwg

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