Derivatives of uracil, intermediate substances, herbicide composition abd method for suppressing weed growth

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention relates to new derivatives of uracil of the formula [I] eliciting the herbicide effect, herbicide composition based on thereof and a method for suppression of weed growth. In the formula [I] W means oxygen (O), sulfur (S) atom or imino-group; Y means oxygen atom (O) or sulfur atom (S); R1 means (C1-C3)-alkyl or (C1-C3)-halogenalkyl; R2 means (C1-C3)-alkyl; R4 means hydrogen atom (H) or methyl; R5 means (C1-C6)-alkyl, (C1-C6)-halogenalkyl, (C3-C6)-alkenyl, (C3-C6)-halogenalkenyl, (C3-C6)-alkynyl or (C3-C6)-halogenalkynyl; X1 means halogen atom, cyano- or nitro-group; X2 means hydrogen atom (H) or halogen atom; each among X3 and X4 means independently hydrogen atom (H), halogen atom, (C1-C6)-alkyl, (C1-C6)-halogenalkyl, (C3-C6)-alkenyl, (C3-C6)-halogenalkenyl, (C3-C6)-alkynyl, (C3-C6)-halogenalkynyl, (C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkoxy-, (C1-C6)-halogenalkoxy-, (C1-C6)-alkoxycarbonyl-(C1-C6)-alkoxy- or cyano-group. Also, invention relates to new intermediate substances used for preparing compounds of the formula [I] corresponding to formulae [VII] , [XXXIV] and [XXXIII] wherein in compound of the formula [VII] W means oxygen (O), sulfur (S) atom or imino-group; Y means oxygen (O) or sulfur atom (S); in compounds of formulae [XXXIV] and [XXXIII] W means oxygen atom (O); R17 means oxygen atom (O); R4 means hydrogen atom (H) or methyl. Also, invention relates to methyl- or ethyl-[2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate not early described in the literature.

EFFECT: valuable herbicide properties of compounds.

23 cl, 17 sch, 9 tbl, 11 ex

 

This invention relates to the derivatives of uracil and their application.

The purpose of this invention is the provision of compounds with excellent herbicide activity.

Recently a large number of herbicides are commercially available and widely used. However, because of the need to deal with numerous types of weeds, reproduction which occurs over an extended period of time, there is a need for herbicide with a broad spectrum herbicide and is not causing problems of phytotoxicity on crops.

In U.S. patent 4859229 argues that certain types fenilatilmalonamid compounds have a weed-killing activity, but these phenylethylenediamine connections do not always have sufficient activity characteristic of herbicides. In WO 97/01541 and WO 98/41093 also indicates that a variety of substituted phenoxyphenylacetic compounds of uracil have a weed-killing activity, however, these compounds do not always have sufficient activity characteristic of herbicides.

The authors of this invention have conducted intensive research in order to find compounds having excellent herbicide activity, and as a result have found that brazilterramar derivatives of the following formula [I] field is with excellent herbicide activity which led to this invention. Namely, this invention provides derivatives of uracil [I] formula [I] (hereinafter called "data connection"):

where W represents oxygen, sulfur, imino or C1-C3-alkylamino, Y denotes oxygen, sulfur, imino or C1-C3-alkylamino, R1represents C1-C3-alkyl or C1-C3-halogenated, R2represents C1-C3-alkyl, R4denotes hydrogen or methyl, R5denotes hydrogen, C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil or3-C6-halogenoalkanes, X1denotes halogen, cyano or nitro, X2denotes hydrogen or halogen, and each of X3and X4independently denotes hydrogen, halogen, C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes, C1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenoalkane,1-C6-alkoxycarbonyl-C1-C6-alkoxy or cyano, and herbicides containing each of these compounds as effective components the NTA.

Further, this invention also provides compounds of aniline [XXXII] formula [XXXII]:

where W represents oxygen, sulfur, imino or C1-C3-alkylamino, R17denotes oxygen or sulfur, R4denotes hydrogen or methyl, R5represents C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes, X1denotes halogen, cyano or nitro, X2denotes hydrogen or halogen, and each of X3and X4independently represent hydrogen, halogen, C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes,1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenoalkane,1-C6-alkoxycarbonyl-C1-C6-alkoxy or cyano,

the compound [XXXIV] formula [XXXIV]:

where W represents oxygen, sulfur, imino or C1-C3-alkylamino, R17denotes oxygen or sulfur, R4denotes hydrogen or methyl, R5represents C1-C6-alkyl, C1-C6-halogenated,3-C6 alkenyl,3-C6-halogenoalkanes,3-C6-quinil or3-C6-halogenoalkanes, R18represents C1-C6-alkyl or phenyl, X1denotes halogen, cyano or nitro, X2denotes hydrogen or halogen, and each of X3and X4independently represent hydrogen, halogen, C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes, C1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenoalkane, C1-C6-alkoxycarbonyl-C1-C6-alkoxy or cyano, and

compound [XXXIII] formula [XXXIII]:

where W represents oxygen, sulfur, imino or C1-C3-alkylamino, R17denotes oxygen or sulfur, R4denotes hydrogen or methyl, R5represents C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil or3-C6-halogenoalkanes, X1denotes halogen, cyano or nitro, X2denotes hydrogen or halogen, and each of X3and X4independently represent hydrogen, halogen, C1-C6-alkyl, C1-C6-halogenated, With3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes,1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenoalkane,1-C6-alkoxycarbonyl-C1-C6-alkoxy or cyano, which are used as intermediates for obtaining these compounds.

In this invention C1-C3-alkylamino represented by W includes methylamino, ethylimino etc.,

C1-C3-alkylamino represented by Y includes methylamino, ethylimino etc.,

C1-C3the alkyl represented by R1denotes methyl, ethyl, propyl, isopropyl,1-C3-halogenated represented by R1includes methyl bromide, chloromethyl, vermeil, dichloromethyl, three-chloromethyl, deformity, trifluoromethyl, pentafluoroethyl, 1,1-dottorati, 3,3,3-cryptochromes etc.,

C1-C3the alkyl represented by R2denotes methyl, ethyl, propyl, isopropyl,

C1-C6the alkyl represented by R5includes methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl and the like, C1-C6-halogenated represented by R5includes methyl bromide, chloromethyl, vermeil, dichloromethyl, trichloromethyl, deformity, CHLOROFORMATES, bromodifluoromethyl, triforma the sludge, pentafluoroethyl, 2-foretel, 1,1-dottorati, 2,2,2-trichloroethyl, 3,3,3-cryptochromes, 3,3,3-trichloropropane etc. With3-C6alkenyl represented by R5includes allyl, 1-methylallyl, 1,1-dimethylallyl, 2-methylallyl, 1-butenyl, 2-butenyl, 3-butenyl etc. With3-C6-halogenoalkanes represented by R5includes 1-chlorallyl, 1-bromall, 2-chlorallyl, 3,3-dichlorethyl etc. With3-C6-quinil represented by R5includes 2-PROPYNYL, 1-methyl-2-PROPYNYL, 1,1-dimethyl-2-PROPYNYL, 2-butynyl, 3-butynyl, 1-methyl-2-butenyl etc. With3-C6-halogenoalkanes represented by R5includes 3-chloro-2-PROPYNYL, 3-bromo-2-PROPYNYL, 1-fluoro-2-PROPYNYL, 1-chloro-2-PROPYNYL, 1-bromo-2-PROPYNYL, 1-chloro-2-butynyl etc.,

C1-C6the alkyl represented by R18includes methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl and the like,

the halogen represented by X1denotes fluorine, chlorine, bromine, iodine,

the halogen represented by X2denotes fluorine, chlorine, bromine, iodine,

the halogen represented by X3and X4denotes fluorine, chlorine, bromine, iodine,

C1-C6the alkyl represented by X3and X4includes methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl and the like, C1-C6-halogenated presented X3and X4includes methyl bromide, chloromethyl, vermeil, dihormati is, trichloromethyl, deformity, CHLOROFORMATES, bromodifluoromethyl, trifluoromethyl, pentafluoroethyl, 2-foretel, 1,1-dottorati, 2,2,2-trichloroethyl, 3,3,3-cryptochromes, 3, 3, 3-trichloropropane etc. With3-C6alkenyl presented X3and X4includes allyl, 1-methylallyl, 1,1-dimethylallyl, 2-methylallyl, 1-butenyl, 2-butenyl, 3-butenyl etc. With3-C6-halogenoalkanes presented X3and X4includes 1-chlorallyl, 1-bromall, 2-chlorallyl, 3,3-dichlorethyl etc. With3-C6-quinil presented X3and X4includes 2-PROPYNYL, 1-methyl-2-PROPYNYL, 1,1-dimethyl-2-PROPYNYL, 2-butynyl, 3-butynyl, 1-methyl-2-butenyl etc. With3-C6-halogenoalkanes presented X3and X4includes 3-chloro-2-PROPYNYL, 3-bromo-2-PROPYNYL, 1-fluoro-2-PROPYNYL, 1-chloro-2-PROPYNYL, 1-bromo-2-PROPYNYL, 1-chloro-2-butynyl etc. With1-C6-alkoxy-C1-C6the alkyl represented by X3and X4includes methoxymethyl, 2-methoxyethyl, 1-methoxyethyl, 3-methoxypropyl, ethoxymethyl, 2-ethoxyethyl, 3-ethoxypropan, isopropoxyphenyl, 2-isopropoxide etc., C1-C6the alkoxy represented by X3and X4includes methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, tert-butoxy etc., C1-C6-halogenoalkane presented X3and X4includes chloromethoxy, Bromma is hydroxy, dichloromethoxy, trichlormethane, triptoreline, 2-floratone, 2,2,2-trichloroethane etc., C1-C6-alkoxycarbonyl-C1-C6the alkoxy represented by X3and X4includes ethoxycarbonylmethoxy, ethoxycarbonylmethoxy, 1 ethoxycarbonylmethoxy, 1 ethoxycarbonylmethoxy, 2-ethoxycarbonylmethoxy, 2-ethoxycarbonylmethoxy etc.

In these preferred compounds are compounds in which R1represents methyl, substituted atom (atoms) fluorine, such as trifluoromethyl, deformity etc. or ethyl, substituted atom (atoms) of fluoride, such as pentafluoroethyl, 1,1-dottorati and the like, more preferably trifluoromethyl, R2represents methyl or ethyl, more preferably methyl, R5represents C1-C3-alkyl, such as methyl, ethyl and propyl, more preferably methyl or ethyl, X1is halogen, more preferably chlorine, X2is halogen, more preferably fluorine, X3represents hydrogen, X4represents hydrogen, W is oxygen and/or Y represents oxygen, from the point of view of herbicide activity. The preferred position of the substitution W on the benzene ring is an ortho-position Y, R4preferably represents hydrogen or methyl, more preferably hydrogen.

In the data the x connections can sometimes be present geometric isomers, due to the presence of a double bond, optical isomers due to the presence of asymmetric carbon, and the diastereoisomer, and this connection includes its isomers and mixtures thereof.

Next will be illustrated how to retrieve data connections.

These compounds may be obtained, for example, the following ways of obtaining ((Method of obtaining 1) - (Method of obtaining 6)).

(Method of obtaining 1)

This compound can be obtained by reaction of the compound [III] of the formula [III]

where R1, R2, W, Y, X1X2X3and X4are as defined above, with the compound [IV] of the formula [IV]

where R4and R5have the above specified values, R6indicates deleted (tsepliaeva) group, such as chlorine, bromine, iodine, methanesulfonate, p-toluensulfonate and the like, in the presence of a base.

This reaction is usually carried out in a solvent at a temperature of usually 0 to 200°C, preferably from 20 to 100°C, for a period of time usually from moment to 72 hours.

In relation to the number of reagents used in this reaction, it is known that the amount of compound [IV] is 1 mol and the amount of the base is 1 mol per 1 mol of compound [III], and these numbers may not necessarily change in hung is on the reaction conditions.

Used the base includes organic bases such as pyridine, quinoline, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, diisopropylethylamine and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydride, potassium hydride, lithium hydroxide, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters, such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; nitro compounds such as nitromethane, nitrobenzene and the like; NITRILES, such as acetonic the sludge, isobutyronitrile and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like; or mixtures thereof.

After completion of the reaction, the target compound can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Next, the compound obtained can be purified by such procedures as chromatography, recrystallization, etc.

(Method of obtaining 2)

The compound [I] of the present compounds in which W is oxygen, can be obtained by reaction of the compound [V] of the formula [V]

where R1, R2, Y, X1X2X3and X4have the above specified values

with alcohol [VI] of the formula [VI]

where R4and R5have the above specified values

in the presence of a dehydrating agent.

This reaction is usually carried out in a solvent at a temperature of usually -20 to 150°C, preferably 0-100°C, for a period of time from moment to 48 hours.

As for ageratifolia agent, lists the combinations of triarylphosphines, such as triphenylphosphine and the like, or trialkylphosphines, such as triethylphosphine and the like, and di(lower alkyl)azodicarboxylate, such as diethylazodicarboxylate, diisopropylsalicylic etc.

In relation to the number of reagents used in this reaction, the amount of alcohol [VI] is 1-3 moles, preferably 1-1 .5 mol, the number of triarylphosphine or trialkylphosphine is 1-3 moles, preferably 1-1 .5 mol, and the amount of di(lower alkyl)azodicarboxylate is 1-3 moles, preferably 1-1,2 mol per 1 mol of compound [V]. The ratio of these reagents is not necessary may vary depending on the reaction conditions.

The solvents used in this reaction include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like, or mixtures thereof.

After completion of the reaction, the target compound can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extra is irout organic solvent and the resulting organic layer is dried and concentrated, the residue is subjected to chromatography.

2) the Reaction solution is directly concentrated and the residue is subjected to chromatography.

Further, the above compound can also be purified by a procedure such as recrystallization, etc.

(Method of obtaining 3)

The compound of this invention can be obtained by reacting carboxylic acid [VII] of the formula [VII]

where R1, R2, R4, W, Y, X1X2X3and X4have the above specified values

and alcohol [VIII] of the formula [VIII]

where R5is above a certain value.

This reaction is carried out, for example, by reacting carboxylic acid {VII] gloriouse agent to obtain the acid chloride (hereinafter this stage is called <Method 3-1>), then the reaction of this acid chloride and compound [VIII] in the presence of a base (hereinafter, this stage is called <Method 3-2>).

<Method 3-1>

This reaction is carried out in the absence of solvent or in a solvent at a temperature of usually from 0 to 150°during the period of time from moment to 24 hours.

In relation to the number of reagents used in this reaction, it is known that the number glorieuses agent is 1 mol per 1 mol of carboxylic acid [VII], and these amounts may not necessarily m is to apply depending on the reaction conditions.

The examples used glorieuses agent include thionyl chloride, sulfurylchloride, phosgene, oxalicacid, trichloride phosphorus, pentachloride phosphorus oxychloride phosphorus, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, Noonan, Dean, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene, mesitylene and the like; aliphatic halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,2,3-trichloropropane and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, 1,4-dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like, or mixtures thereof.

After completion of the reaction, for example, the reaction solution was concentrated and the residue used directly in the <Method 3-2>.

<Method 3-2>

This reaction is carried out in the absence of solvent or in the solvent at the reaction temperature is usually -20 to 100°during the period of time from moment to 24 hours.

In relation to the number of reagents used in this reaction, it is known that the number of alcohol [VIII] and the amount of the base is 1 mol 1 mol carbó the OIC acid [VII], used in <Method 3-1> and their number can optionally be changed depending on the reaction conditions.

Examples of the base include inorganic bases such as sodium bicarbonate, potassium bicarbonate, lithium carbonate, sodium carbonate, potassium carbonate and the like, nitrogen-containing aromatic compounds such as pyridine, quinoline, 4-dimethylaminopyridine, 2-picoline, 3-picoline, 4-picoline, 2,3-lutidine, 2,4-lutidine, 2,5-lutidine, 2,6-lutidine, 3,4-lutidine, 3,5-lutidine, 3-chloropyridine, 2-ethyl-3-methylpyridine, 5-ethyl-2-methylpyridine and the like, tertiary amines such as triethylamine, diisopropylethylamine, tri-n-Propylamine, tri-n-butylamine, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane and the like,

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, Noonan, Dean, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene, mesitylene and the like; aliphatic halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,2,3-trichloropropane and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl e is Il, diisopropyl ether, methyl tert-butyl ether, 1,4-dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like, or mixtures thereof.

After completion of the reaction, the target compound can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Further, the above compound can also be purified by this procedure, as chromatography, recrystallization, etc.

This reaction is not limited to the above-mentioned methods can also be performed using the method in which the reaction is carried out in the presence of a condensing agent such as 1,1'-carbonyldiimidazole, 1,3-dicyclohexylcarbodiimide and the like, using the method in which the reaction is carried out in the presence of an acid catalyst, and other known methods.

(Method 4)

The compound [I] of the present compounds in which X1represents nitro or cyano, may be obtained by the interaction of compounds derived uracil [IX] of the formula [IX]

where R1, R2and X2have defined is installed above the value R7represents fluorine, chlorine, bromine or iodine and X11is nitro or cyano,

with the compound [X] of the formula [X]

where R4, R5, W, Y, X3and X4have some higher values, in the presence of a base.

This reaction is carried out in the absence of solvent or in a solvent at a temperature of usually from 0 to 200°and for a period of time usually from moment to 24 hours.

In relation to the number of reagents used in this reaction, it is known that the amount of compound [X] is 1 mol and the amount of the base is 1 mol per 1 mole of the uracil derivative [IX], and these quantities can optionally be changed depending on the reaction conditions.

Used the base includes organic bases such as pyridine, quinoline, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, diisopropylethylamine and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydride, potassium hydride, lithium hydroxide, sodium hydroxide, hydroxide CA the Oia, calcium hydroxide, barium hydroxide, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters, such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; nitro compounds such as nitromethane, nitrobenzene and the like; NITRILES, such as acetonitrile, isobutyronitrile and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like; or mixtures thereof.

This reaction can sometimes be accelerated by using a catalyst. As a catalyst can be used copper iodide, copper bromide, copper chloride, copper powder, etc. and the amount of catalyst used in this reaction is from 0.0001 to 0.1 mole per 1 mole of the uracil derivative [IX], and these quantities can optionally be changed depending on conditions reacts is I.

After completion of the reaction, the target compound can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Further, the above compound can also be purified by this procedure, as chromatography, recrystallization and the like(the Method of obtaining 5)

The compound [I] of the present compounds in which X1represents fluorine, chlorine, bromine or iodine, can be obtained using the following schema.

where R1, R2, R4, R5, W, X2X3and X4have the above specified values, X12represents fluorine, chlorine, bromine or iodine and Y1represents oxygen, sulfur, imino or alkylamino.

<Method 5-1>: the Method of obtaining the compound [XII] from the compound [XI].

The compound [XII] can be obtained, for example, by recovering the compound [XI] the iron powder in the presence of acid in the solvent.

This reaction is carried out in the absence of solvent or in a solvent at a temperature of usually from 0 to 200°C, preferably from room temperature to t is mperature reflux distilled. The reaction time is usually a period from a moment to 24 hours.

In relation to the number of reagents used in this reaction, the amount of iron powder is from 3 mol to excess, and the amount of acid is from 1 mol to 10 mol per 1 mol of compound [XI], and these quantities can optionally be changed depending on the reaction conditions.

As for the acid to be used, it is possible to produce acetic acid, etc.

As for the used solvent can be, for example, water, acetic acid, ethyl acetate, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained in the normal operation subsequent processing, for example by filtration, and then by pouring the reaction solution into water and collecting osadivshih crystals by filtration, or by extraction with an organic solvent, neutralization, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

<Method 5-2>: the Method of obtaining the compound [XIII] from the compound [XII].

The compound [XIII] can be obtained (i) by diazotization of the compound [XII] in the solvent, and then (ii) reaction of diazocompounds with potassium iodide, copper bromide (I)chloride copper (I) or a mixture of hydrofluoric acid with boric acid (hereinafter called emeu hydromorphinol acid) depending on the target compound, in the solvent.

The reaction of diazotization of the first stage is carried out at a temperature of usually -20 to 20°With over a period of time usually from moment to 5 hours.

In relation to the number of reagents used in this reaction, it is known that the number diastereomer agent is 1 mol per 1 mol of compound [XII], and these quantities can optionally be changed depending on the reaction conditions.

As used diastereomer agent can be called nitrites such as sodium nitrite, potassium nitrite, isoamylase, tert-butylnitrite etc.

As used solvent can be named, for example, acetonitrile, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

After completion of the reaction, the reaction solution used in that form in which it is located, in the following reaction.

The second stage reaction is carried out at a temperature between 0-80°With over a period of time usually from moment to 24 hours.

In relation to the number of reagents used in this reaction, the amount each of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid is from 1 to 3 mol per 1 mol of compound [XII], and these quantities can optionally be changed depending on the reaction conditions.

When using copper bromide (I) reaction of mo the et also be carried out in the presence of copper bromide (II), when using a copper chloride (I) the reaction may also be carried out in the presence of copper chloride (II).

As for the used solvent can be, for example, acetonitrile, diethyl ether, tert-butyl methyl ether, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

After completion of the reaction, the target compound can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Then, the obtained this compound can also be purified by this procedure, as chromatography, recrystallization and the like (see Org. Syn. Coll. Vol.2, 604 (1943), Vol.1, 136 (1932))

This reaction is not limited to the above-mentioned ways, and receiving can be carried out also by the interaction of the compound [XII] with diasterous agent in a solvent in the presence of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid depending on the target compound (see Heterocycles., 38, 1581 (1994), and so on).

When using copper bromide (I) the reaction may also be carried out in the presence of copper bromide (II), and when and the use of copper chloride (I) the reaction may also be carried out in the presence of copper chloride (II).

(Method of obtaining 6)

This compound can be obtained by the interaction of the derivative of uracil [XXXI] formula [XXXI]

where R1, R4, R5, W, Y, X1X2X3and X4are as defined above, with the compound [XXXX] of the formula [XXXX]

where R18is removed (tsepliaeva) group, such as chlorine, bromine, iodine, methanesulfonate, p-toluene-sulfonyloxy and the like, and R2has the above specified values, in the presence of a base.

This reaction is usually carried out in the absence of solvent or in the solvent at the reaction temperature is usually from 0 to 200°C, preferably from 20 to 100°for the period of time from moment to 24 hours.

In relation to the number of reagents used in this reaction, it is known that the number of connections [XXXX] is 1 mol and the amount of the base is 1 mol per 1 mol of compound [XXXI], and these quantities can optionally be changed depending on the reaction conditions.

Used the base includes organic bases such as pyridine, quinoline, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethyl is in, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, diisopropylethylamine and the like, alkoxides of metals such as sodium methoxide, ethoxide sodium tert-piperonyl potassium and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydride, potassium hydride, lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters, such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; nitro compounds such as nitromethane, nitrobenzene and the like; NITRILES, such as acetonitrile, isobutyronitrile and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfur compounds such as dimethylsulfate the ID, sulfolane and the like; alcohols such as methanol, ethanol, ethylene glycol, isopropanol, tert-butanol and the like, or mixtures thereof.

After completion of the reaction, the target compound can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Then, the obtained this compound can also be purified by this procedure, as chromatography, recrystallization, etc.

Alcohol [VI], alcohol [VIII] and the compound [X], used in the methods of this invention can be obtained by known methods or are commercially available materials.

Carboxylic acid [VII] can be obtained by acid hydrolysis of this compound [I].

Some of the intermediate products used for obtaining this compound can be obtained, for example, using the following methods to obtain ((a Method of obtaining 1 of intermediate products) - (Method of obtaining 6 intermediate products)).

(Method 1 obtain intermediate products)

The compound [III]in which W and Y represent oxygen or sulfur (i.e., the compound [XIX]), and connect the out [XIV] can be also obtained by the method, described in the following diagram.

where R1, R2, R7X2X3X4and X12have the above specified values, each of R15and R17independently represents oxygen or sulfur and R16represents a protective group such as a silyl group such as tert-butyldimethylsilyl etc.; C1-C6-alkyl which may be substituted, such as tert-butyl, methyl and the like; benzyl which may be substituted, such as benzyl and the like; methoxymethyl, acetyl, meloxicam-nil, etoxycarbonyl etc.

<Method A1-1>: the Method of producing compound [XIV] from compound [XXXXI]

The compound [XIV] can be obtained by reacting compound [HHHHI] with the compound [XXXXII] in the presence of a base.

This reaction is usually carried out in the absence of solvent or in a solvent, at a temperature of usually 0 to 200°and for a period of time from moment to 24 hours.

In relation to the number of reagents used in this reaction, it is known that the number of connections [XXXXII] is 1 mol and the amount of the base is 1 mol per 1 mol of compound [XXXXI], and these quantities can optionally be changed depending on the reaction conditions.

Used the base includes organic bases such as pyridine, quinoline, benzyldimethylamine, Hairdryer shall childinitiated, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, diisopropylethylamine and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, hydride sodium, potassium hydride, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters, such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; nitro compounds such as nitromethane, nitrobenzene and the like; NITRILES, such as acetonitrile, isobutyronitrile and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfur compounds such as dimethylsulfoxide, Sul is Folan etc., or mixtures thereof.

After completion of the reaction, the target compound can be obtained, for example, the following operations 1), 2) or 3).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2), the Reaction mixture was poured into water and saducees crystals are collected by filtration.

3) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Further, the above compound can also be purified by this procedure, as chromatography, recrystallization, etc.

<Method A1-2>: the Method of producing compound [XVI] from the compound [XIV].

The compound [XVI] can be obtained by reacting compound [XIV] with the compound [XV] in the presence of a base.

This reaction is usually carried out in the absence of solvent or in a solvent, at a temperature of usually -20 to 200°C, preferably from -5 to 80°With, usually over a period of time from moment to 24 hours.

In relation to the number of reagents used in this reaction, it is known that the amount of compound [XV] is 1 mol and the amount of the base is 1 mol per 1 mol of compound [XIV], and these quantities can optionally be changed depending on the reaction conditions.

Used base which includes organic bases, such as pyridine, quinoline, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, diisopropylethylamine and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydride, potassium hydride, lithium hydroxide, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters, such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; nitro compounds such as nitromethane, nitrobenzene and the like; NITRILES, such as acetonitrile, isobutyronitrile and the like; acid amides such as N,N-dimethyl who formamid, N,N-dimethylacetamide and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like, or mixtures thereof.

After completion of the reaction, the target compound can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer was washed with hydrochloric acid, then brine, dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Next, the compound obtained can be purified by such procedures as chromatography, recrystallization, etc.

<Method A1-3>: the Method of obtaining the compound [XVII] from the compound [XVI].

The compound [XVII] can be obtained, for example, by reduction of compound [XVI] using iron powder in the presence of acid in the solvent.

The reaction temperature is usually from 0 to 200°C, preferably from room temperature to the temperature of reflux distilled. The reaction time is usually a period from a moment to 24 hours.

In relation to the number of reagents used in this reaction, the amount of iron powder is from 3 mol to excess, and the amount of acid is 1 to 10 mol per 1 mol of compound [XVI], and these quantities can NeoMaster is but can vary depending on the reaction conditions.

The acid can be used acetic acid, etc.

As a solvent, can be used, for example, water, acetic acid, ethyl acetate, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained in the normal operation subsequent processing, such as filtering, then pouring the reaction solution into water and collecting osadivshih crystals by filtration, or extraction of the reaction solution with an organic solvent, neutralization, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

<Method A1-4>: the Method of obtaining the compound [XVIII] from the compound [XVII].

The compound [XVIII] can be obtained (i) by diazotization of the compound [XVII] in the solvent, and then (ii) reaction of diazocompounds with potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid in a solvent.

The reaction of diazotization of the first stage is carried out at the reaction temperature is usually from -20 to 20°With, usually over a period of time from moment to 5 hours.

In relation to the number of reagents used in this reaction, it is known that the number diastereomer agent is 1 mol per 1 mol of compound of General formula [XVII], and these quantities can optionally be changed depending on the conditions the reaction.

As diastereomer agent can be used nitrites such as sodium nitrite, potassium nitrite, isoamylase, tert-butylnitrite etc.

The solvent can be used, for example, acetonitrile, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

The reaction solution after completion of the reaction used in this form, it is in the next reaction.

The second stage reaction is carried out at a temperature of 0-80°and usually for a period of time from moment to 24 hours.

In relation to the number of reagents used in this reaction, the amount each of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid is from 1 to 3 mol per 1 mol of compound [XVII], and these quantities can optionally be changed depending on the reaction conditions. When using copper bromide (I) the reaction may also be carried out in the presence of copper bromide (II), and the use of copper chloride (I) the reaction may also be carried out in the presence of copper chloride (II).

As for the used solvent can be, for example, acetonitrile, diethyl ether, tert-butyl methyl ether, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

After completion of the reaction target the second connection can be obtained using conventional subsequent processing, such as collecting the resulting crystals by filtration (if necessary, by adding water) or extraction with an organic solvent, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

Further, this reaction is not limited to the above methods, and the receipt can also be carried out by reacting the compound [XVII] diastereomer agent in a solvent (for example, acetonitrile, diethyl ether, tert-butyllithium ether, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or their mixtures) in the presence of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid (see Heterocycles., 38, 1581 (1994), and so on).

<Method A1-5>: the Method of producing compound [XIX] from the compound [XVIII].

The compound [XIX] can be obtained by removing the protective groups (deprotection) compound [XVIII] using tribromide boron, HBr/acetic acid, concentrated hydrochloric acid, concentrated sulfuric acid or TPV accordance with the method described in Protective Groups in Organic Synthesis (Protective groups in organic synthesis) (published by A Wiley-Interscience publication).

Here, in the case of compound [XVIII], where R16represents benzyl which may be substituted, such ka is benzyl, the compound [XIX] can be also obtained by hydrogenation of compound [XVIII] in the presence of a catalyst.

This reaction is usually carried out in a solvent at a temperature of usually -20°to 150°C, preferably from 0 to 50°C, for a period of time usually from moment to 48 hours. This reaction may also be conducted under positive pressure and typically this reaction is carried out under a pressure of 1-5 atmospheres.

The amount of catalyst used in this reaction is 0.001 to 100% by weight based on the compound [XVIII].

As a catalyst in this reaction it is possible to use anhydrous palladium on coal, water-containing palladium on charcoal, platinum oxide, etc.

The solvent includes carboxylic acids such as formic acid, acetic acid, propionic acid and the like, esters such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; ethers such as 1,4-dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol and the like; alcohols such as methanol, ethanol, isopropanol and the like; water, or a mixture thereof.

After completion of the reaction, the target material can be obtained using conventional processing, such as filtering the reaction solution prior to concentration of the solution or pouring the reaction solution into water before filtration of the resulting crystals, or ylvania reaction solution in water and exposure to the mixture of extraction with an organic solvent, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

(Method 2 obtain intermediate products)

The compound [III]in which W signifies NH (i.e., the compound [XXIII]), can be obtained according to the method described in the following schema.

where R1, R2, R7, Y, X1X2X3and X4have the above specified values.

<Method A2-1>: the Method of producing compound [XXII] from the compound [XX]

The compound [XXII] can be obtained by reacting compound [XX] with the compound [XXI] in the presence of a base.

This reaction is usually carried out in the absence of solvent or in a solvent, at a temperature of usually from 0 to 200°With, usually over a period of time from moment to 24 hours.

In relation to the number of reagents used in this reaction, it is known that the amount of compound [XXI] is 1 mol and the amount of the base is 1 mol per 1 mol of compound [XX], and these quantities can optionally be changed depending on the reaction conditions.

Used the base includes organic bases such as pyridine, quinoline, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]OCTA is, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, diisopropylethylamine and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydride, potassium hydride, lithium hydroxide, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters, such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; nitro compounds such as nitromethane, nitrobenzene and the like; NITRILES, such as acetonitrile, isobutyronitrile and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like; or mixtures thereof.

This reaction can sometimes be accelerated by ka is alistor.

The amount of catalyst used in this reaction is preferably from 0.0001 to 0.1 mol per 1 mol of compound [XX], and these quantities can optionally be changed depending on the reaction conditions.

As a catalyst can be used copper iodide, copper bromide, copper chloride, copper powder, etc.

After completion of the reaction, the target compound can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Next, the compound obtained can be purified by such procedures as chromatography, recrystallization, etc.

<Method A2-2>: the Method of obtaining the compound [XXIII] from the compound [XXII]

The compound [XXIII] can be obtained, for example, by reduction of compound [XXII] the iron powder in the presence of acid in the solvent.

The reaction is usually carried out at temperatures from 0 to 200°C, preferably from room temperature to the temperature of reflux distilled over a period of time from moment to 24 hours.

In relation to the number of reagents used in this reaction, the amount of iron powder SOS the defaults from 3 mol to excess, and the amount of acid is from 1 to 10 mol per 1 mol of compound [XXII], moreover, these quantities can optionally be changed depending on the reaction conditions.

The acid can be used acetic acid, etc.

As a solvent, can be used, for example, water, acetic acid, ethyl acetate, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained in the normal operation subsequent processing, such as filtering, then collecting the resulting crystals by filtration (if necessary, by adding water) or extraction with an organic solvent, neutralization, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

(Method 3 obtain intermediate products)

The compound [III]in which W represents an oxygen (i.e., the compound [V])can be obtained according to the method described in the following schema.

where R1, R2, Y, X1X2X3and X4have the above specified values.

The compound [V] can be obtained (i) by the interaction of the compound [XXIII] diastereomer agent in the solvent, and then (ii) heating of this product in the acid solvent or permission salt of copper to act on this product in the presence of a catalyst containing copper.

The first reaction stevepavlina at a temperature of usually -20 to 10° During the period of time from moment to 5 hours.

In relation to the number of reagents used in this reaction, it is known that the number diastereomer agent is 1 mol per 1 mol of compound [XXIII], and these quantities can optionally be changed depending on the reaction conditions.

As diastereomer agent can be used nitrites such as sodium nitrite, potassium nitrite, isoamyl-nitrite, tert-butylnitrite etc.

The solvent can be used, for example, acetonitrile, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

The reaction solution after completion of the reaction used in this form, it is in the next reaction.

In the reaction, heating the acid in the solvent of the second stage, the reaction temperature is from 60°to the temperature of reflux distilled, and the reaction time is usually a period from moment to 48 hours.

As the acid solvent include, for example, hydrochloric acid, Hydrobromic acid, sulfuric acid, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained using conventional processing, such as collecting the resulting crystals by filtration (if necessary, by adding water is) or extraction with an organic solvent, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

The reaction of interaction of copper salt in the presence of a copper-containing catalyst in the second stage is carried out in a solvent at a temperature of from 0°to the temperature of reflux distilled, and over a period of time from moment to 24 hours.

In relation to the number of reagents used in this reaction, the amount of copper-containing catalyst is 0.001-5 mol and the amount of salt of copper is 1-100 mol per 1 mol of compound [XXIII], and these quantities can optionally be changed depending on the reaction conditions.

As catalyst containing copper, lists the copper oxide (I) and the like, as well as salts of copper are listed sulfate copper (II)nitrate copper (II), etc.

The solvent can be used, for example, water, hydrochloric acid, sulfuric acid, etc. or mixtures thereof.

After completion of the reaction, the target compound can be obtained using conventional processing, such as extraction with an organic solvent, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

(Method 4 obtain intermediate products)

The compound [IX] can be received is on the way described in the following diagram.

where R1, R2, R7X2and X11have the above specified values.

The compound [IX] can be obtained by diazotization of compound [XXIV] in the solvent, then the reaction diazocompounds with a halogenation agent.

<the First stage (reaction of diazotization)>

the reaction temperature: -20 to 20°

reaction time: from moment up to 5 hours

the number diastereomer agent is from 1 mol to excess

on 1 mol of compound [XXIV]

diasterous agent: nitrites such as sodium nitrite,

soliditet, tert-butylnitrite etc.

solvent: acetonitrile, hydrochloric acid and

so

<a Second phase>

the reaction temperature is 0 to 80°

reaction time: from instant to 24 hours

the amount of halogenation agent: 1 to 3 mol per 1

mol of compound [XXIV]

halogenation agent: potassium iodide, copper bromide (I),

chloride copper (I) or hydromorphone acid, etc.

solvent: acetonitrile, hydrochloric acid and

so

The compound [IX] can be also obtained by the interaction of the compound [XXIV] diastereomer agent in a solvent in the presence of a halogenation agent.

the reaction temperature is 0 to 80°

reaction time: from moment to 48 hours

the number d is asterousia agent is from 1 mol to excess

on 1 mol of compound [XXIV]

diasterous agent: nitrites, such as isoamylase,

tert-butylnitrite etc.

the amount of halogenation agent: 1 to 3 mol per 1

mol of compound [XXIV]

halogenation agent: potassium iodide, copper bromide (I),

chloride copper (I) or hydromorphone acid, etc.

solvent: acetonitrile, etc.

When using copper bromide (I) the reaction may also be carried out in the presence of copper bromide (II), and the use of copper chloride (I) the reaction may also be carried out in the presence of copper chloride (II).

(Method 5 obtain intermediate products)

The compound [X], in which W represents an oxygen or sulfur (i.e., the compound [XXVI]), can be obtained according to the method described in the following schema.

where R4, R5, R6, R15, Y, X3and X4have the above specified values.

The compound [XXVI] can be obtained by reaction of the compound [XXV] with the compound [IV] in a solvent in the presence of a base.

the reaction temperature is 0 to 200°

reaction time: from moment to 72 hours

the amount of compound [IV]: 1-3 mol per 1 mol of compound [XXV]

a number of reasons: 1-3 mol per 1 mol of compound [XXV]

base: triethylamine, potassium carbonate, sodium hydride and

so

solvent: tetrahydrofuran, acetonic the sludge, N,N-dimethylformamide, dimethylsulfoxide, methanol, water, etc. or mixtures thereof.

(Method 6 obtain intermediate products)

The compound [X]in which Y represents oxygen or sulfur (i.e., the compound [XXX]), can be obtained according to the method described in the following schema.

where R4, R5, R6, R16, R17, W, n, X3and X4have the above specified values.

<Method A6-1>: the Method of producing compound [XXVIII] from compound [XXVII]

The compound [XXVIII] can be obtained by reaction of the compound [XXVII] with tert-butyldimethylsilyloxy, Isobutanol, benzylchloride, benzylbromide etc.(see Protective Groups in Organic Synthesis (Protective groups in organic synthesis) (published by A Wiley-Interscience publication)).

<Method A6-2>: the Method of obtaining the compound [XXIX] from compound [XXVIII]

The compound [XXIX] can be obtained by reaction of the compound [XXVIII] with the compound [IV] in a solvent in the presence of a base.

the reaction temperature is 0 to 200°

reaction time: from moment to 72 hours

the amount of compound [IV]: 1-3 mol per 1 mol of compound [XXVIII]

a number of reasons [IV]: 1-3 mol per 1 mol of compound [XXVIII]

base: triethylamine, potassium carbonate, sodium hydride, etc.

solvent: tetrahydrofuran, acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, methanol, water, etc. sludge is a mixture.

<Method A6-3>: the Method of producing compound [XXX] from the compound [XXIX]

The compound [XXX] can be obtained by removing the protective groups of the compound [XXIX] according to the method described in "Yuki Called Jikken no Tebiki (published by Manual of Organic Chemical Experiment)", vol.4, (published by Called Dojin sha), Protective Groups in Organic Synthesis (Protective groups in organic synthesis) (published by A Wiley-Interscience publication). Specifically, the compound [XXIX]in which R18represents silyl, such as tert-butyldimethylsilyl etc. can be freed from the protective groups by reaction triperoxonane acid or tetrabutylammonium, etc. in a solvent such as methylene chloride, ethyl acetate, water or the like, the Compound [XXIX]in which R18represents benzyl which may be substituted, such as benzyl and the like, can be freed from the protective groups by reaction with hydrogen in the presence of a catalyst.

the reaction temperature: -20 to 150°C, preferably from 0 to 50°

reaction time: from moment to 48 hours

the amount of catalyst is from 0.001 to 100% for all compounds [XXIX]

catalyst: anhydrous palladium on coal, water-containing palladium on charcoal, platinum oxide, etc.

solvent: acetic acid, ethyl acetate, methanol, etc.

(Method 7 obtain intermediate products)

The compound [XXXI]in which Y represents oxygen or sulfur, can be floor is constrained by the way, described in the following diagram.

where R1, R4, R5, R7, R17, W, X1X2X3and X4have the above specified values, R18represents C1-C6-alkyl (e.g. methyl, ethyl and the like) or phenyl, R13represents C1-C6-alkyl (e.g. methyl, ethyl and the like)

<Method A7-1>: the Method of obtaining the compound [XXXII] from compound [XXXVI]

The compound [XXXII] can be obtained by converting compound [XXXVI] in the compound [XXXII], then the reaction with the compound [XXXVIII] (see Bioorganics and Medicinal Chemistry Letters, vol.5, p.1035 (1995).

<Method A7-2>: the Method of producing compound [XXXIII] from the compound [XXXII]

The compound [XXXIII] can be obtained by the method in accordance with the known method described in U.S. patent 4859229 etc., from the compound [XXXII].

Specifically, the compound [XXXIII] can be obtained from the cyanide compound [XXXII] in a solvent or in the absence of solvent.

Isocyanide agent: phosgene, trichloromethylcarbonate, oxalicacid etc.

The number isocyanides agent is from 1 mole to excess per 1 mole of compound [XXXII]

Solvent: aromatic hydrocarbons, such as benzene, toluene and the like, halogenated aromatic hydrocarbons, such as chlorobenzene and the like, esters such as ethylacetate etc.

The reaction temperature from room temperature to the temperature of reflux distilled

Reaction time: from moment to 48 hours

After completion of the reaction, the target material can be obtained by concentrating the reaction solution, etc. This compound can also be purified by such an operation as recrystallization, etc.

<Method A7-3>: the Method of obtaining the compound [XXXIV] from the compound [XXXII]

The compound [XXXIV] can be obtained by the method in accordance with the known method described in U.S. patent 4879229 etc., from the compound [XXXII].

Specifically, the compound [XXXIV] can be obtained by the interaction of the compound [XXXII] with the compound [b-4] of the formula [b-4]

where R18and X12have the above specified values

in the presence of a base.

This reaction is usually conducted in a solvent, and it can also be carried out in the absence of a solvent at a temperature of usually -20 to 200°C, for a period of time usually from moment to 48 hours.

The amount of compound [b-4]used in this reaction is from 0.5 mol to excess, preferably from 1.0 to 1.2 mol, per 1 mol of compound [XXXII].

The amount of base used in this reaction is from 0.5 mol to excess, preferably from 1.0 to 1.2 mol, per 1 mol of compound [XXXII].

The base includes neorg the technical Foundation, such as sodium carbonate, sodium hydroxide and the like, organic bases such as pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, aminobutiramida-ethylamine, etc.

The solvent includes aliphatic halogenated hydrocarbons such as chloroform and the like, ethers such as tetrahydrofuran, 1,4-dioxane and the like, NITRILES such as acetonitrile and the like, esters such as ethyl acetate, water or their mixtures, etc.

After completion of the reaction, the target material can be obtained using conventional subsequent processing, for example, by filtration of the reaction solution before concentration or by pouring the reaction solution into water and collecting the resulting crystals by filtration, or by pouring the reaction solution into water and exposure to this mixture, extraction with an organic solvent, concentration and the like, This material can be purified by the procedure as recrystallization, chromatography and so on

<Method A7-4>: the Method of producing compound [XXXIX] from compound [XXXIII]

The compound [XXXIX] can be obtained according to the method described in U.S. patent 4879229 etc., from compound [XXXIII] and the compound [XXXV].

Specifically, the compound [XXXIX] can be obtained by reaction of the compound [XXXIII] with the compound [XXXV] in a solvent in the presence of base is.

The amount of compound [XXXV]: from 0.5 mol to excess, preferably from 0.8 to 1.2 mol per 1 mol of compound [XXXIII]

Base: inorganic base such as sodium hydride and the like, alkoxides of metals such as lithium methoxide, ethoxide sodium, etc.

A number of reasons: from 0.5 mol to excess, preferably from 0.8 to 1.2 mol per 1 mol of compound [XXXIII]

Solvent: aromatic hydrocarbons, such as benzene, toluene and the like; halogenated aromatic hydrocarbons such as chlorobenzene and the like; amides such as N,N-dimethylformamide and the like; ethers such as tetrahydrofuran and the like, halogenated aliphatic hydrocarbons, such as chloroform and the like; sulfur compounds such as dimethylsulfoxide and the like, and mixtures thereof

The reaction temperature: -40°to the temperature of reflux distilled solvent

Reaction time: from moment to 72 hours

After completion of the reaction, the target material can be obtained using conventional subsequent processing, for example, by filtration of the reaction solution before concentration or by adding acid to the reaction solution, and collecting the resulting crystals by filtration or by adding acid to the reaction solution, followed by exposure to this mixture, extraction with an organic solvent, the concentration, the other As an added acid can be used hydrochloric acid, acetic acid, triperoxonane acid, p-toluensulfonate acid or their aqueous solutions and the like, This material can be purified by the procedure as recrystallization, chromatography and so on

The obtained compound [XXXIX] can also be subjected to the reaction with the compound [XXXX] in accordance with the method described in (production Method of 6), without performing subsequent processing, such as selection and so on, receiving this connection.

<Method A7-5>: the Method of producing compound [XXXIX] from the compound [XXXIV]

The compound [XXXIX] can be obtained according to the method described in U.S. patent 4879229 etc., from the compound [XXXIV] and the compound [XXXV].

Specifically, the compound [XXXIX] can be obtained by reacting compound [XXXIV] with the compound [XXXV] in the presence of a base.

This reaction is usually carried out in a solvent at a temperature of usually -20 to 200°C, preferably from 0 to 130°With over a period of time usually from moment to 72 hours.

The amount of compound [XXXV]used in this reaction is from 0.5 mol to excess, preferably from 0.8 to 1.2 mol, per 1 mol of compound [XXXIV].

The amount of base used in this reaction is from 0.5 mol to excess, preferably from 0.8 to 1.2 mol, per mol compound [XXXIV].

The base includes organic bases such as 4-dimethylaminopyridine, diisopropylethylamine and the like, inorganic bases such as sodium carbonate, potassium carbonate, sodium hydride, potassium hydride and the like, alkoxides of metals such as sodium methoxide, ethoxide sodium tert-piperonyl potassium, etc.

The solvent includes ketones such as acetone, methyl isobutylketone and the like, aliphatic hydrocarbons such as hexane, heptane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, mesitylene and the like; ethers such as diethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, methyl tert-butyl ether and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; tertiary amines such as pyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, diisopropylethylamine and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like, or mixtures thereof, etc.

After completion of the reaction, the target material can be obtained using conventional subsequent processing, for example, by filtration of the reaction solution before concentration or by adding acid to the reaction solution, and collecting the resulting crystals by filtration or by adding water to the reaction solution, C is the exposure to this mixture, extraction with an organic solvent, the concentration, etc. as the added acid can be used hydrochloric acid, acetic acid, triperoxonane acid, p-toluensulfonate acid or their aqueous solutions and the like, This material can be purified by the procedure as recrystallization, chromatography and so on

The obtained compound [XXXIX] can also be subjected to the reaction with the compound [XXXX] in accordance with the method described in (production Method of 6), without performing subsequent processing, such as selection and so on, receiving this connection.

(Method 8 obtain intermediate products)

The compound [III]in which Y and W are oxygen and sulfur, can also be obtained by the method described in the following schema.

where R1, R2, R15, R16, R17X2X3and X4have the above specified values, R20represents C1-C6-alkyl which may be substituted, such as methyl, ethyl, trifluoromethyl, trichloromethyl and the like, R26represents C1-C6-alkyl which may be substituted, such as methyl, ethyl and the like, phenyl which may be substituted, such as phenyl and the like, or phenyl-C1-C6-alkyl which may be substituted, such as benzyl and the like, and X13is nitro, the torus, chlorine, bromine or iodine.

<Method A8-1>: the Method of producing compound [a-2] from the compound [a-1]

The compound [a-2] can be obtained, for example, removing the protective groups of the compound [a-1] according to the method described in "Yuki Called Jikken no Tebiki (published by Manual of Organic Chemical Experiment)", vol. 4, (published by Called Dojin sha), Protective Groups in Organic Synthesis (Protective groups in organic synthesis) (published by A Wiley-Interscience publication) or in accordance with the following method.

This reaction is usually carried out in the absence of solvent or in a solvent at a temperature of usually from 0 to 200°With over a period of time usually from moment to 24 hours. With regard to the amount of the reagents used in this reaction, it is known that the quantity of reagent equal to 1 mol per 1 mol of compound [a-1], and these quantities can optionally be changed depending on the reaction conditions. As used reagents can be named diethylether of boron TRIFLUORIDE, a complex of boron TRIFLUORIDE-methanol, triaminotrinitrobenzene etc. as used solvent can be called aliphatic hydrocarbons such as hexane, heptane, octane, ligroin and the like; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, mesitylene and the like; aliphatic halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,2,3-tri ochropus etc.; aromatic halogenated hydrocarbons, such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as 1,4-dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, methyl tert-butyl ether and the like, alcohols such as methanol, ethanol and the like, or mixtures thereof, etc.

After completion of the reaction, the target material can be obtained using conventional subsequent processing, for example by pouring the reaction solution into water, collecting the resulting crystals by filtration and drying them, or by extraction with an organic solvent and drying and concentrating the organic layer or the concentration of the reaction solution and the like, This material can be purified by the procedure as recrystallization, chromatography and so on

<Method A8-2>: the Method of producing compound [a-3] from the compound [a-2]

The compound [a-3] can be obtained by reaction of the compound [a-2] with the compound [b-1] formula [b-1]

where R26and X12have some higher values, in the presence of a base.

This reaction is usually conducted in a solvent, and it can also be carried out in the absence of a solvent at a temperature of usually -20 to 200°With over a period of time usually from moment to 48 hours.

The amount of compound [b-1]used in the section of the reaction, is from 0.5 mol to excess, preferably from 1.0 to 1.2 mol, per 1 mol of compound [a-2].

The amount of base used in this reaction is from 0.5 mol to excess, preferably from 1.0 to 1.2 mol, per 1 mol of compound [a-2].

The base includes inorganic bases such as sodium carbonate, sodium hydroxide and the like, organic bases such as pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, aminobutiramida-ethylamine, etc.

The solvent includes aliphatic halogenated hydrocarbons such as chloroform and the like, ethers such as tetrahydrofuran, 1,4-dioxane and the like, NITRILES such as acetonitrile and the like, esters such as ethyl acetate, water or their mixtures, etc.

After completion of the reaction, the target material can be obtained using conventional subsequent processing, for example, by filtration of the reaction solution before concentration or by pouring the reaction solution into water and collecting the resulting crystals by filtration, or by pouring the reaction solution into water and exposure to this mixture, extraction with an organic solvent, concentration and the like, This material can be purified by the procedure as recrystallization, chromatography and so on

<Method A8-3>: the Method of gaining the compound [a-5] from the compound [a-3]

The compound [a-5] can be obtained by the interaction of the compound [a-3] with the compound [XXXV] in the presence of a base.

This reaction is usually carried out in a solvent at a temperature of usually -20 to 200°C, preferably from 0 to 130°C, for a period of time usually from moment to 72 hours.

The amount of compound [XXXV]used in this reaction is from 0.5 mol to excess, preferably from 0.8 to 1.2 mol, per 1 mol of compound [a-3].

The amount of base used in this reaction is from 0.5 mol to excess, preferably from 0.8 to 1.2 mol, per 1 mol of compound [a-3].

The base includes organic bases such as 4-dimethylaminopyridine, diisopropylethylamine and the like, inorganic bases such as sodium carbonate, potassium carbonate, sodium hydride, potassium hydride and the like, alkoxides of metals such as sodium methoxide, ethoxide sodium tert-piperonyl potassium, etc.

The solvent includes ketones such as acetone, methyl isobutylketone and the like, aliphatic hydrocarbons such as hexane, heptane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, mesitylene and the like; ethers such as diethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, methyl tert-butyl ether and the like; nitro compounds, that is their as nitromethane, nitrobenzene and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; tertiary amines such as pyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, visapro-militiamen and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like, or mixtures thereof, etc.

After completion of the reaction, the target material can be obtained using conventional subsequent processing, for example by filtration of the reaction solution before concentration or by adding acid to the reaction solution, and collecting the resulting crystals by filtration, or by adding water to the reaction solution, followed by exposure to this mixture, extraction with an organic solvent, concentration, etc. as the added acid can be used hydrochloric acid, acetic acid, triperoxonane acid, p-toluensulfonate acid or their aqueous solutions and the like, This material can be purified by the procedure as recrystallization, chromatography and the like, Further, the compound [a-5] can also be used in the next reaction without highlighting.

<Method A8-4>: the Method of producing compound [a-4] from the compound [a-2]

The compound [a-4] can be obtained by isocyanatophenyl compound [a-2] in a solvent or in the absence of solvent.

Isocyanide the agent: phosgene, trichloromethylcarbonate, oxalicacid etc.

The number isocyanides agent: from 1 mole to excess per 1 mole of compound [a-2]

Solvent: aromatic hydrocarbons, such as benzene, toluene and the like, halogenated aromatic hydrocarbons, such as chlorobenzene and the like, esters such as ethyl acetate, etc.

The reaction temperature from room temperature to the temperature of reflux distilled

Reaction time: from moment to 48 hours

After completion of the reaction, the target material can be obtained by concentrating the reaction solution, etc. This compound can also be purified by such an operation as recrystallization, etc.

<Method A8-5>: the Method of producing compound [a-5] from the compound [a-4]

The compound [a-5] can be obtained by reaction of the compound [a-4] with the compound [XXXV] in a solvent in the presence of a base.

The amount of compound [XXXV]: from 0.9 mol to 10 mol per 1 mol of compound [a-4]

Base: inorganic base such as sodium hydride, potassium hydroxide, sodium hydroxide and the like, alkoxides of metals such as sodium methoxide, ethoxide sodium, etc.

A number of reasons: from 0.1 mol to 10 mol per 1 mol of compound [a-4]

Solvent: aromatic hydrocarbons, such as benzene, toluene and the like; halogenated aromatic coal is hydrogens, such as chlorobenzene and the like; amides such as N,N-dimethylformamide and the like; ethers such as tetrahydrofuran and the like, halogenated aliphatic hydrocarbons, such as chloroform and the like; sulfur compounds such as dimethylsulfoxide and the like, and mixtures thereof

The reaction temperature: -40°to the temperature of reflux distilled solvent

Reaction time: from moment to 72 hours

After completion of the reaction, the target material can be obtained using conventional subsequent processing, for example, neutralization, followed by pouring the reaction solution into water and collecting osadivshih crystals and drying them, or by extraction with an organic solvent and drying and concentrating the organic layer, or by concentrating the reaction solution, and the like, This material can be purified by the procedure as recrystallization, chromatography and so on

The obtained compound [a-5] can also be used in the next reaction without highlighting.

<Method A8-6>: the Method of producing compound [a-6] from the compound [a-5]

The compound [a-6] can be obtained by reaction of the compound [a-5] with the compound [XXXX] in the presence of a base.

This reaction is usually carried out in a solvent at a temperature of usually -20 to 200°C, preferably from 0 to 100°C, for a period of time as is but from moment to 48 hours.

The number of connections [XXXX]used in this reaction is from 0.5 mol to excess, preferably from 0.8 to 1.2 mol, per 1 mol of compound [a-5].

The amount of base used in this reaction is from 0.5 mol to excess, preferably from 0.8 to 1.2 mol, per 1 mol of compound [a-5].

The base includes organic bases such as pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, diisopropylethylamine and the like; inorganic bases such as sodium carbonate, potassium carbonate, sodium hydride, potassium hydride, etc.

The solvent includes aliphatic hydrocarbons such as hexane, heptane, octane, ligroin, cyclohexane and the like; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, mesitylene and the like; ethers such as diethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, methyl tert-butyl ether and the like; nitro compounds such as nitromethane, nitrobenzene and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; tertiary amines, such as pyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, diisopropylethylamine and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like; alcohols such as methanol, ethanol, ethylene glycol, isopropanol, tertbutanol etc.; or mixtures thereof, etc.

After completion of the reaction, the target material can be obtained using conventional subsequent processing, for example, by filtration of the reaction solution before concentration or by pouring the reaction solution into water and collecting the resulting crystals, or by pouring the reaction solution into water, followed by extraction with an organic solvent, concentration, etc.

This compound can also be purified by the procedure as recrystallization, chromatography and so on

<Method A8-7>: the Method of producing compound [a-7] from the compound [a-6]

The compound [a-7] can be obtained in accordance with Method A1-5 Method 1 to obtain an intermediate product from the compound [a-6].

(Method 9 obtain intermediate products)

The compound [a-1] can be obtained according to the method described in the following diagram. (In this scheme, the compound [a-1] is represented as the compound [a-9] or the compound [a-11]).

where R7, R15, R16, R17, R20X2X3X4and X12have the above specified values.

<Method A9-1>: the Method of producing compound [a-9] from the compound [a-8]

The compound [a-9] can be obtained by reaction of the compound [a-8] with the compound [XV] in the presence of a base.

This reactions is usually carried out in the absence of solvent or in a solvent at a temperature of usually from 0 to 200° With over a period of time usually from moment to 24 hours.

In relation to the number of reagents used in this reaction, it is known that the amount of compound [XV] is 1 mol and the amount of the base is 1 mol per 1 mol of compound [a-8], and these quantities can optionally be changed depending on the reaction conditions.

Used the base includes organic bases such as pyridine, quinoline, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, diisopropylethylamine and the like, alkoxides of metals such as sodium methoxide, ethoxide sodium tert-piperonyl potassium and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydride, potassium hydride, lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic ha is generowanie hydrocarbons, such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; nitro compounds such as nitromethane, nitrobenzene and the like; NITRILES, such as acetonitrile, isobutyronitrile and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like; alcohols such as methanol, ethanol, ethylene glycol, isopropanol, tert-butanol and the like, or mixtures thereof.

After completion of the reaction, the target material can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Next, the target material can also be recycled through this procedure as chromatography, recrystallization, etc.

<Method A9-2>: the Method of producing compound [a-10] from the compound [a-9]

The compound [a-10] can be floor is, however, for example, the reconnection [a-9] the iron powder in the presence of acid in the solvent.

This reaction is usually conducted at a temperature of from 0 to 200°C, preferably from room temperature to the temperature of reflux distilled over a period of time usually from moment to 24 hours.

In relation to the number of reagents used in this reaction, the amount of iron powder is from 3 mol to excess, and the amount of acid is from 1 mol to 10 mol per 1 mol of compound [a-9], and these quantities can optionally be changed depending on the reaction conditions.

The acid can be used acetic acid, etc.

The solvent can be used, for example, water, acetic acid, ethyl acetate, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained in the normal operation subsequent processing, such as pouring the reaction solution into water immediately or after filtering and collecting the resulting crystals, or extraction with an organic solvent, neutralization, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

<Method A9-3>: the Method of producing compound [a-11] from the compound [a-10]

The compound [a-11] can be obtained (i) by diazotization of compound [is -10] in the solvent, then ii) by the reaction of diazocompounds with potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid in a solvent.

The reaction of diazotization of the first stage is carried out at a temperature of usually -20 to 20°With over a period of time usually from moment to 5 hours.

In relation to the number of reagents used in this reaction, it is known that the number diastereomer agent is 1 mol per 1 mol of compound [a-10], and these quantities can optionally be changed depending on the reaction conditions.

As diastereomer agent can be used nitrites such as sodium nitrite, potassium nitrite, isoamylase, tert-butylnitrite etc.

As used solvent can be named, for example, acetonitrile, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

The reaction solution after completion of the reaction used in this form, it is in the next reaction.

The second stage reaction is carried out at a temperature of 0-80°With over a period of time usually from moment to 24 hours.

In relation to the number of reagents used in this reaction, the amount each of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid is from 1 to 3 mol per 1 mol of compound [a-10], and these quantities which may optionally be changed depending on the reaction conditions. When using copper bromide (I) the reaction may also be carried out in the presence of copper bromide (II), and the use of copper chloride (I) the reaction may also be carried out in the presence of copper chloride (II).

As for the used solvent can be, for example, acetonitrile, diethyl ether, tert-butyl methyl ether, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained by collecting the resulting crystals by filtration (if necessary, by adding water or by extraction with an organic solvent, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

Further, this reaction is not limited to the above methods, and the receipt can also be carried out by reaction of the compound [a-10] diastereomer agent in a solvent (for example, acetonitrile, diethyl ether, tert-butyllithium ether, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or their mixtures) in the presence of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid.

(Method 10 obtain intermediate products)

The compound [III]in which X1represents nitro, fluorine, chlorine, bro is or iodine, and Y and W are oxygen or sulfur, can be obtained according to the method described in the following schema.

where R1, R2, R7, R17X2X3X4and X12have the above specified values.

<Method a10-1>: the Method of producing compound [a-12] from the compound [XIV]

The compound [a-12] can be obtained by the interaction of the compound [XIV] with the compound [b-2] of the formula [b-2]

where R17X3and X4have some higher values, in the presence of a base.

This reaction is usually carried out in the absence of solvent or in a solvent at a temperature of usually from 0 to 200°With over a period of time usually from moment to 24 hours.

In relation to the number of reagents used in this reaction, it is known that the amount of compound [b-2] is 1 mol and the amount of the base is 1 mol per 1 mol of compound [XIV], and these quantities can optionally be changed depending on the reaction conditions.

Used the base includes organic bases such as pyridine, quinoline, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, tri-n-Propylamine, Diisopropylamine, tri-n-butylamine, diisopropylethylamine and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters, such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; nitro compounds such as nitromethane, nitrobenzene and the like; NITRILES, such as acetonitrile, isobutyronitrile and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like; or mixtures thereof.

After completion of the reaction, the target material can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Next, the target material can also be recycled through this procedure as chromatography, recrystallization, etc.

<Method a10-2>: the Method of producing compound [a-13] from the compound [a-12]

The compound [a-13] can be obtained, for example, by reduction of compound [a-12] the iron powder in the presence of acid in the solvent.

This reaction is usually conducted at a temperature of from 0 to 200°C, preferably from room temperature to the temperature of reflux distilled over a period of time usually from moment to 24 hours.

With regard to the amount of the reagents used in this reaction, the amount of iron powder is from 3 mol to excess, and the amount of acid is from 1 mol to 10 mol per 1 mol of compound [a-12], and these quantities can optionally be changed depending on the reaction conditions.

The acid can be used acetic acid, etc.

The solvent can be used, for example, water, acetic acid, ethyl acetate, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained by pouring the reaction solution into water immediately or after filtering and collecting the resulting crystals, or by extraction with an organic solvent, neutralization, concentration, etc.

The whole is howl material can also be recycled such procedure, as chromatography, recrystallization, etc.

<Method a10-3>: the Method of producing compound [a-14] from the compound [a-13]

The compound [a-14] can be obtained (i) by diazotization of the compound [a-13] in the solvent, and then (ii) reaction of diazocompounds with potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid in a solvent.

The reaction of diazotization of the first stage is carried out at a temperature of usually -20 to 20°and usually for a period of time from moment to 5 hours.

In relation to the number of reagents used in this reaction, it is known that the number diastereomer agent is 1 mol per 1 mol of compound [a-13], and these quantities can optionally be changed depending on the reaction conditions.

As diastereomer agent that can be used, can be called nitrites such as sodium nitrite, potassium nitrite and the like, organic compounds nitrous acid, such as isoamylase, tert-butylnitrite etc.

As used solvent can be named, for example, acetonitrile, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

The reaction solution after completion of the reaction used in this form, it is in the next reaction.

The second stage reaction is carried out at a temperature which e 0-80° And usually for a period of time from moment to 24 hours.

With regard to the amount of the reagents used in this reaction, the amount each of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid is from 1 to 3 mol per 1 mol of compound [a-13], and these quantities can optionally be changed depending on the reaction conditions. When using copper bromide (I) the reaction may also be carried out in the presence of copper bromide (II), and the use of copper chloride (I) the reaction may also be carried out in the presence of copper chloride (II).

The solvent can be used, for example, acetonitrile, diethyl ether, tert-butyl methyl ether, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained by collecting the resulting crystals by filtration (if necessary, by adding water or by extraction with an organic solvent, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

Further, this reaction is not limited to the above-mentioned ways, and receiving can be carried out also by the interaction of the compound [a-13] diastereomer agent in a solvent (e.g. acetonitrile, Diatlov is m the air, tert-butyllithium ether, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or their mixtures) in the presence of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid.

(Method 11 obtain intermediate products)

The compound [III]in which Y and W are oxygen, may be obtained according to the method described in the following schema.

where R1, R2, R20X1X2X3and X4have the above specified values.

<Method A11-1>: the Method of producing compound [a-16] from the compound [a-15]

The compound [a-16] can be obtained, for example, removing the protective groups of the compound [a-15] according to the method described in "Yuki Called Jikken no Tebiki (published by Manual of Organic Chemical Experiment)", vol. 4, (published by Called Dojin sha), Protective Groups in Organic Synthesis (Protective groups in organic synthesis) (published by A Wiley-Interscience publication) or in accordance with the following method.

The above reaction is usually carried out in the absence of solvent or in a solvent at a temperature of usually from 0 to 200°and usually for a period of time from moment to 24 hours. In relation to the number of reagents used in this reaction, it is known that the quantity of reagent equal to 1 mol per 1 mol of compound [a-15], and these quantities can optionally be changed depending on autoclave reaction. As used reagents can be called the complex of boron TRIFLUORIDE-methanol, triaminotrinitrobenzene etc. as used solvent can be called aliphatic hydrocarbons such as hexane, heptane, octane, ligroin and the like; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, mesitylene and the like; aliphatic halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,2,3-trichloropropane and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as 1,4-dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, methyl tert-butyl ether and the like, alcohols such as methanol, ethanol and the like, or mixtures thereof, etc.

After completion of the reaction, the target material can be obtained from a conventional subsequent processing, for example by pouring the reaction solution into water and collecting the resulting crystals by filtration and drying them, or by extraction with an organic solvent and drying and concentrating the organic layer, or by concentrating the reaction solution, and the like, This material can be purified by the procedure as recrystallization, chromatography and so on

<Method A11-2>: the Method of obtaining compound a-17] from the compound [a-16]

The compound [a-17] can be obtained by isocyanatophenyl connection [a-16] in the solvent or in the absence of solvent.

Isocyanide agent: phosgene, trichloromethylcarbonate, oxalicacid etc.

The number isocyanides agent: from 1 mole to excess per 1 mole of compound [a-16]

Solvent: aromatic hydrocarbons, such as benzene, toluene and the like, halogenated aromatic hydrocarbons, such as chlorobenzene and the like, esters such as ethyl acetate, etc.

The reaction temperature from room temperature to the temperature of reflux distilled

Reaction time: from moment to 48 hours

After completion of the reaction, the target material can be obtained by concentrating the reaction solution, etc. This compound can also be purified by such an operation as recrystallization, etc.

<Method A11-3>: the Method of producing compound [a-18] from the compound [a-17]

The compound [a-18] can be obtained by reaction of the compound [a-17] with the compound [XXXV] in a solvent in the presence of a base.

The amount of compound [XXXV]: from 0.9 mol to 10 mol per 1 mol of compound [a-17]

Base: inorganic base such as sodium hydride, potassium hydride, sodium hydroxide, and the like, alkoxides of metals such as sodium methoxide, ethoxide sodium, etc.

A number of reasons: from 0.1 mol to 1 mol per 1 mol of compound [a-17]

Solvent: aromatic hydrocarbons, such as benzene, toluene and the like; halogenated aromatic hydrocarbons such as chlorobenzene and the like; amides such as N,N-dimethylformamide and the like; ethers such as tetrahydrofuran and the like, halogenated aliphatic hydrocarbons, such as chloroform and the like; and mixtures thereof

The reaction temperature: -40°to the temperature of reflux distilled solvent

Reaction time: from moment to 72 hours

After completion of the reaction, the target material can be obtained using a conventional subsequent processing, for example, neutralization, followed by pouring the reaction solution into water and collecting osadivshih crystals by filtration, or by extraction with an organic solvent and drying and concentrating the organic layer, or by concentrating the reaction solution, and the like, This material can be purified by the procedure as recrystallization, chromatography and so on

The compound [a-18] can also be used in the next reaction without highlighting.

<Method A11-4>: the Method of producing compound [a-29] from the compound [a-18]

The compound [a-29] can be obtained by reaction of the compound [a-18] with the compound [XXXX] in the presence of a base.

This reaction is usually carried out in a solvent at a temperature of usually -20 to 200°Ave doctitle from 0 to 100° And usually for a period of time from moment to 48 hours.

The number of connections [XXXX]used in this reaction is from 0.5 mol to excess, preferably from 0.8 to 1.2 mol, per 1 mol of compound [a-18].

The amount of base used in this reaction is from 0.5 mol to excess, preferably from 0.8 to 1.2 mol, per 1 mol of compound [a-18].

The base includes organic bases such as pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, diisopropylethylamine and the like; inorganic bases such as sodium carbonate, potassium carbonate, sodium hydride, potassium hydride, etc.

The solvent includes aliphatic hydrocarbons such as hexane, heptane, octane, ligroin, cyclohexane and the like; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, mesitylene and the like; ethers such as diethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, methyl tert-butyl ether and the like; nitro compounds such as nitromethane, nitrobenzene and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; tertiary amines, such as pyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, diisopropylethylamine and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like, or mixtures thereof, etc.

the donkey is complete, the reaction of the target material can be obtained using a conventional subsequent processing, for example, by filtration of the reaction solution before concentration or by pouring the reaction solution into water and collecting the resulting crystals, or by pouring the reaction solution into water, then the exposure to this mixture, extraction with an organic solvent, concentration, etc. This compound can also be purified by the procedure as chromatography, recrystallization, etc.

(Method 12 obtain intermediate products)

The compound [XXXII], where X1represents nitro, fluorine, chlorine, bromine or iodine, can also be obtained by the method described in the following schema.

where R4, R5, R7, R17, R20, W, X2X3X4and X13have the above specified values.

<Method A12-1>: the Method of producing compound [a-20] from the compound [a-19]

The compound [a-20] can be obtained by the interaction of the compound [a-19] with the compound [b-3] of the formula [b-3]

where R4, R5, R17, W, Y, X3and X4have some higher values, in the presence of a base.

This reaction is usually carried out in the absence of solvent or in a solvent at a temperature of usually from 0 to 200°and usually for a period of time from moment to 24 hours.

In relation to the number of Reagan is s, used in this reaction, it is known that the amount of compound [b-3] is 1 mol and the amount of the base is 1 mol per 1 mol of compound [a-19], and these quantities can optionally be changed depending on the reaction conditions.

Used the base includes organic bases such as pyridine, quinoline, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, diisopropylethylamine and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydride, potassium hydride, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, t is such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; nitro compounds such as nitromethane, nitrobenzene and the like; NITRILES, such as acetonitrile, isobutyronitrile and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like; or mixtures thereof.

After completion of the reaction, the target material can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Next, the target material can also be recycled through this procedure as chromatography, recrystallization, etc.

<Method A12-2>: the Method of producing compound [a-21] from the compound [a-20]

The compound [a-21] can be obtained, for example, by reduction of compound [a-20] the iron powder in the presence of acid in the solvent.

This reaction is usually carried out at temperatures from 0 to 200°C, preferably from room temperature to the temperature of reflux distilled, usually over a period of time from moment to 24 hours.

As to the amount of the reagent is in, to be used in this reaction, the amount of iron powder is from 3 mol to excess, and the amount of acid is from 1 mol to 10 mol per 1 mol of compound [a-20], and these quantities can optionally be changed depending on the reaction conditions.

The acid can be used acetic acid, etc.

The solvent can be used, for example, water, acetic acid, ethyl acetate, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained using a conventional subsequent processing, for example by pouring the reaction solution into water immediately or after filtering and collecting the resulting crystals by filtration, or by extraction with an organic solvent, neutralization, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

<Method A12-3>: the Method of producing compound [a-22] from the compound [a-21]

The compound [a-22] can be obtained (i) by diazotization of the compound [a-21] in the solvent, and then (ii) reaction of diazocompounds with potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid in a solvent.

In the diazotization reaction of the first stage, the reaction temperature is equal to is usually from -20 to 20°and the reaction time is usually the period from mg is ovenia up to 5 hours.

In relation to the number of reagents used in this reaction, it is known that the number diastereomer agent is 1 mol per 1 mol of compound [a-21], and these quantities can optionally be changed depending on the reaction conditions.

As diastereomer agent can be used nitrites such as sodium nitrite, potassium nitrite, isoamylase, tert-butylnitrite etc.

The solvent can be used, for example, acetonitrile, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

The reaction solution after completion of the reaction used in this form, it is in the next reaction.

The second stage reaction is carried out at a temperature of 0-80°and usually for a period of time from moment to 24 hours.

With regard to the amount of the reagents used in this reaction, the amount each of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid is from 1 to 3 mol per 1 mol of compound [a-21], and these quantities can optionally be changed depending on the reaction conditions. When using copper bromide (I) the reaction may also be carried out in the presence of copper bromide (II), and the use of copper chloride (I) the reaction may also be carried out in the presence of copper chloride (II).

As dissolve what I can use, for example, acetonitrile, diethyl ether, tert-butyl methyl ether, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained using a conventional subsequent processing, for example, collecting the resulting crystals (if necessary, by adding water or by extraction with an organic solvent, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

Further, this reaction is not limited to the above-mentioned ways, and receiving can be carried out also by the interaction of the compound [a-21] diastereomer agent in a solvent (for example, acetonitrile, diethyl ether, tert-butyllithium ether, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or their mixtures) in the presence of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid.

When using copper bromide (I) the reaction may also be carried out in the presence of copper bromide (II), and the use of copper chloride (I) the reaction may also be carried out in the presence of copper chloride (II).

<Method A12-4>: the Method of producing compound [a-23] from the compound [a-22]

The compound [a-23] can be obtained, for example, adelinaselmani groups of compounds [a-22] according to the method, described in "Yuki Called Jikken no Tebiki (published by Manual of Organic Chemical Experiment)", vol.4, (published by Called Dojin sha), Protective Groups in Organic Synthesis (Protective groups in organic synthesis) (published by A Wiley-Interscience publication) or in accordance with the following method.

This reaction is usually carried out in the absence of solvent or in a solvent at a temperature of usually from 0 to 200°and usually for a period of time from moment to 24 hours. In relation to the number of reagents used in this reaction, it is known that the quantity of reagent equal to 1 mol per 1 mol of compound [a-22], and these quantities can optionally be changed depending on the reaction conditions. As used reagents can be called the complex of boron TRIFLUORIDE-methanol, triaminotrinitrobenzene etc. as used solvent can be called aliphatic hydrocarbons such as hexane, heptane, octane, ligroin and the like; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, mesitylene and the like; aliphatic halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,2,3-trichloropropane and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as 1,4-dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, methyl-tert-Buti is new ether and the like, alcohols, such as methanol, ethanol and the like, or mixtures thereof, etc.

After completion of the reaction, the target material can be obtained using a conventional subsequent processing, for example by pouring the reaction solution into water and collecting the resulting crystals by filtration and drying them, or by extraction with an organic solvent and drying and concentrating the organic layer, or by concentrating the reaction solution, and the like, This material can be purified by the procedure as recrystallization, chromatography and so on

<Method A12-5>: the Method of producing compound [a-23] from the compound [a-20]

The compound [a-23], where X13is nitro can be obtained in accordance with the method described in <Method A12-4>from the compound [a-20].

(Method 13 obtain intermediate products)

The compound [XXXIV] and the compound [a-15], where X1represents nitro, fluorine, chlorine, bromine or iodine, the compound [a-20] and the compound [a-22] can also be obtained using the methods described in the following diagram.

where R4, R5, R7, R17X2X3X4X12and X13have the above specified values, R25represents C1-C6-alkyl which may be substituted, such as methyl, ethyl, three is tormentil, trichloromethyl and the like; or C1-C6-alkoxy which may be substituted, such as methoxy, ethoxy and the like; or phenoxy, which may be substituted, such as phenoxy etc.

<Method A13-1>: the Method of producing compound [a-25] from the compound [a-24]

The compound [a-25] can be obtained by reaction of the compound [a-24] with the compound [b-2] in the presence of a base.

This reaction is usually carried out in the absence of solvent or in a solvent at a temperature of usually from 0 to 200°and usually for a period of time from moment to 24 hours.

In relation to the number of reagents used in this reaction, it is known that the amount of compound [b-2] is 1 mol and the amount of the base is 1 mol per 1 mol of compound [a-24], and these quantities can optionally be changed depending on the reaction conditions.

Used the base includes organic bases such as pyridine, quinoline, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, N, N-dimethylaniline, N,N-diethylaniline, triethylamine, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, diisopropylethylamine and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, hydrocarbon is tons of sodium, the potassium bicarbonate, sodium hydride, potassium hydride, lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters, such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; nitro compounds such as nitromethane, nitrobenzene and the like; NITRILES, such as acetonitrile, isobutyronitrile and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like; or mixtures thereof.

This reaction can sometimes be accelerated by using a catalyst. As the catalyst are listed copper iodide, copper bromide, copper chloride, copper powder and the like, and the amount of catalyst used in this reaction is from 0.0001 to 0.1 mol per 1 mol of compound [a-24], being the m these quantities can optionally be changed depending on the reaction conditions.

After completion of the reaction, the target material can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Next, the target material can also be recycled through this procedure as chromatography, recrystallization, etc.

<Method A13-2>: the Method of producing compound [a-26] from the compound [a-25]

The compound [a-26] can be obtained, for example, by reduction of compound [a-25] the iron powder in the presence of acid in the solvent.

This reaction is usually carried out at temperatures from 0 to 200°C, preferably from room temperature to the temperature of reflux distilled, usually over a period of time from moment to 24 hours.

With regard to the amount of the reagents used in this reaction, the amount of iron powder is from 3 mol to excess, and the amount of acid is from 1 mol to 10 mol per 1 mol of compound [a-25], and these quantities can optionally be changed depending on the reaction conditions.

The acid can be used acetic acid, etc.

The solvent can be used, for example the EP, water, acetic acid, ethyl acetate, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained using conventional subsequent processing, for example by pouring the reaction solution into water immediately or after filtering and collecting the resulting crystals by filtration, or by extraction with an organic solvent, neutralization, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

<Method A13-3>: the Method of producing compound [a-27] from the compound [a-26]

The compound [a-27] can be obtained (i) by diazotization of the compound [a-26] in the solvent, and then (ii) reaction of diazocompounds with potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid in a solvent.

The reaction of diazotization of the first stage is carried out at the reaction temperature is usually from -20 to 20°and for a period of time usually from moment to 5 hours.

In relation to the number of reagents used in this reaction, it is known that the number diastereomer agent is 1 mol per 1 mol of compound [a-26], and these quantities can optionally be changed depending on the reaction conditions.

As diastereomer agent that can be used, can be called nitrites such as sodium nitrite, n the threat of potassium, soliditet, tert-butylnitrite etc.

As used solvent can be named, for example, acetonitrile, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

The reaction solution after completion of the reaction used in this form, it is in the next reaction.

The second stage reaction is conducted at a temperature of 0-80°and for a period of time usually from moment to 24 hours.

With regard to the amount of the reagents used in this reaction, the amount each of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid is from 1 to 3 mol per 1 mol of compound [a-26], and these quantities can optionally be changed depending on the reaction conditions. When using copper bromide (I) the reaction may also be carried out in the presence of copper bromide (II), and the use of copper chloride (I) the reaction may also be carried out in the presence of copper chloride (II).

As a solvent, can be used, for example, acetonitrile, diethyl ether, tert-butyl methyl ether, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or mixtures thereof.

After completion of the reaction, the target material can be obtained using conventional processing, such as picking up forming the camping crystals by filtration (if necessary, by adding water or by extraction with an organic solvent, concentration, etc.

The target material can also be recycled such procedure as chromatography, recrystallization, etc.

Further, this reaction is not limited to the above-mentioned ways, and receiving can be carried out also by the interaction of the compound [a-26] diastereomer agent in a solvent (for example, acetonitrile, diethyl ether, tert-butyllithium ether, Hydrobromic acid, hydrochloric acid, sulfuric acid, water, etc. or their mixtures) in the presence of potassium iodide, copper bromide (I)chloride copper (I) or hydromorphone acid.

When using copper bromide (I) the reaction may also be carried out in the presence of copper bromide (II), and the use of copper chloride (I) the reaction may also be carried out in the presence of copper chloride (II).

<Method A13-4>: the Method of producing compound [a-28] from the compound [a-27]

The compound [a-28] can be obtained by the interaction of the compound [a-27] with the compound [IV] in the presence of a base.

This reaction is usually carried out in a solvent at a temperature of usually from 0 to 200°and for a period of time usually from moment to 72 hours.

In relation to the number of reagents used in this reaction, it is known that the amount of compound [IV] is 1 mol and the amount of base Rav is about 1 mol per 1 mol of compound [a-27], and these quantities can optionally be changed depending on the reaction conditions.

Used the base includes organic bases such as pyridine, quinoline, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, diisopropylethylamine and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydride, potassium hydride, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters, such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; NITRILES, such as and ethical, isobutyronitrile and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfur compounds such as dimethylsulfoxide, sulfolane and the like; or mixtures thereof.

After completion of the reaction, the target material can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Next, the target material can also be recycled through this procedure as chromatography, recrystallization, etc.

<Method A13-5>: the Method of producing compound [a-28] from the compound [a-25]

The compound [a-28], where X13is nitro can be obtained by reaction of the compound [a-25] with the compound [IV] in the presence of a base.

This reaction is usually carried out in a solvent at a temperature of usually from 0 to 200°and for a period of time usually from moment to 72 hours.

In relation to the number of reagents used in this reaction, it is known that the amount of compound [IV] is 1 mol and the amount of the base is 1 mol per 1 mol of compound [a-25], and these quantities can optionally be changed depending on the reaction conditions.

Used the base includes organic bases, such as pyridine, quinoline, benzyldimethylamine, penicillamin, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, N,N-dimethylaniline, N,N-diethylaniline, triethylamine, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, diisopropylethylamine and the like, and inorganic bases such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, barium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydride, potassium hydride, etc.

Examples of the solvent include aliphatic hydrocarbons such as n-hexane, n-heptane, ligroin, cyclohexane, petroleum ether and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, benzotrifluoride and the like; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol, diglyme and the like; ketones, such as acetone, 2-butanone, methyl isobutyl ketone and the like; esters, such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; NITRILES, such as acetonitrile, isobutyronitrile and the like; acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; sulfur compounds such as dimetilan XID, sulfolane and the like; or mixtures thereof.

After completion of the reaction, the target material can be obtained, for example, the following operations 1) or 2).

1) the Reaction solution was poured into water, extracted with an organic solvent and the resulting organic layer is dried and concentrated.

2) the Reaction solution concentrate directly or filtered, if necessary, before concentrating the filtrate.

Next, the target material can also be recycled through this procedure as chromatography, recrystallization and the like(Method 14 obtain intermediate products)

The compound [III]in which W is oxygen, can be also obtained by the method described in the following schema.

where R1, R2, R6X1X2X3X4and Y are as defined above values, R23represents formyl, alkylsulphonyl, which may be substituted, such as acetyl and the like, or alkoxycarbonyl, which may be substituted, such as methoxycarbonyl and the like, and R24represents hydrogen, alkyl which may be substituted, such as methyl and the like, or alkoxy which may be substituted, such as methoxy.

(Method 15 obtain intermediate products)

The compound [III]in which X4represents hydrogen, fluorine, chlorine, bromine and the iodine, can be obtained by the method described in the following schema.

where R1, R2, R6, R16, W, X1X2X3X12and Y have the above specified values.

(Method 16 obtain intermediate products)

The compound [a-25] and [a-27], in which R25defined as R20can be also obtained by the method described in the following schema.

where R16, R17, R20X2X3X4and X13have the above specified values.

The compound [a-42] can be obtained from compound [a-41] according to the method described in Protective Groups in Organic Synthesis (Protective groups in organic synthesis) (published by A Wiley-Interscience publication) using tribromide bromine, HBr/acetic acid, concentrated hydrochloric acid or concentrated sulfuric acid, etc.

The amount of reagent from 1 mole to excess per 1 mole of compound [a-41]

Solvent: aromatic hydrocarbons, such as benzene, toluene and the like; halogenated aliphatic hydrocarbons, such as methylene chloride, chloroform and the like, halogenated aromatic hydrocarbons, such as chlorobenzene and the like, or mixtures thereof.

The reaction temperature: -20°to the temperature of reflux distilled

Reaction time: from moment to 48 hours

the donkey completion of this reaction, the target material can be obtained using conventional subsequent processing, for example by pouring the reaction solution into water or by adding acid, such as concentrated hydrochloric acid, etc. to the reaction solution and collecting osadivshih crystals by filtration, or by extraction of the reaction solution with an organic solvent and drying and concentrating the organic layer, or by concentrating the reaction solution, and the like, This material can be purified by the procedure as recrystallization, chromatography and so on

In the case of compound [a-41], in which R16represents benzyl which may be substituted, the compound [a-42] can also be obtained from compound [a-41] the hydrogenation in the presence of a catalyst.

This reaction is usually carried out in a solvent at a temperature of usually -20°to 150°C, preferably from 0 to 50°C, for a period of time from moment to 48 hours.

This reaction can also be carried out under pressure, and usually the reaction is carried out under a pressure of 1-5 atmospheres.

The amount of catalyst used in this reaction is 0.001 to 100% by weight based on the compound [a-41].

As the catalyst used in this reaction can be called anhydrous palladium on charcoal, palladium containing water is and coal the oxide of platinum, etc.

The solvent includes carboxylic acids such as formic acid, acetic acid, propionic acid and the like, esters such as ethyl formate, ethyl acetate, butyl acetate, diethylmalonate and the like; ethers such as 1,4-dioxane, tetrahydrofuran, dimethyl ether of ethylene glycol and the like; alcohols such as methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, amyl alcohol, isoamyl alcohol, tert-amyl alcohol and the like; water, or a mixture thereof, etc.

After completion of the reaction, the target material can be obtained using the normal operations subsequent processing, such as filtering the reaction solution before concentrating the solution, etc. of the Target material can also be recycled such procedure as recrystallization, chromatography and so on

Connection [XXXXII] can be obtained, for example, by the method described in WO 98/08824, or by the method described in this publication, and the connection [XXXXI], compound [XXI], compound [XXIV], compound [XX] and the compound [XXV] can be obtained by known methods or can be used commercially available products.

These compounds possess excellent herbicide activity and some of them can show excellent selectivity between cultivated plants and weeds. In other words, data from the unity have a weed-killing activity against a variety of weeds, which can cause anxiety, when spraying the leaves and soil on upland fields, such as those listed below.

weeds of the family Onagraceae:

large-flowered evening primrose (Oenothera erythrosepala), evening primrose with globalroutinename leaves (Oenothera laciniata),

weeds of the family Ranunculaceae Ranunculaceae:

Buttercup maghiwalay (Ranunculus muricatus), Buttercup Sardinian (Ranunculus sardous)

weeds buckwheat family (Polygonaceae):

Highlander vjunkovye (Polygonum convolvulus), Highlander pale (Polygonum lapathiolium), Highlander Pennsylvania (Polygonum pensylvanicum), Highlander pochechuynogo (Polygonum persicaria), sorrel curly (Rumex crispus), sorrel tupolisty (Rumex obtusifolius), Highlander pointed (Japanese) (Polygonum cuspidatum)

weeds of the family Portulacaceae:

the garden purslane (Portulaca oleracea)

weeds of the family Caryophyllaceae:

starwort average (Stellaria media), cerastium skuchenkova (Cerastium glomeratum)

weeds of the goosefoot family (Chenopodiaceae):

the white pigweed (Chenopodium album), Kochia (Kochia scoparia)

weeds of the family of Amaranthaceae:

amaranth spiked (Amaranthus retroflexus, Amaranthus hybrid (Amarenthus hybridus)

weeds of the mustard family (Brassicaceae):

the wild radish (Raphanus raphanistrum), white mustard (Sinapis arvensis), shepherd's purse (Capsella bursa-pastoris), Virginia peppergrass (Lepidium virginicum)

weeds (Leguminosae):

sesbania (Sesbania exaltata), Cassia (Cassia obtusifolia), Florida clover (poverty grass) (Desmodium tortuosum), clover Trifolium repens repens), common vetch (Vicia sativa), alfalfa cholevidae (Medicago lupilina)

weeds of the Malvaceae family:

canetic Theophrastus (Abutilon Theophrasti), breast prickly Sida spinosa)

weeds of the violet family (Violaceae):

violet field (Viola arvensis), wild Pansy (Viola tricolor)

weeds of the family Rubiaceae:

cleaver (Gallium aparine)

weeds of the family Vukovich (Convolvulaceae):

bindweed bluelily (Ipomoea hederacea), bindweed purple

(Ipomoea purpurea), morning glory zelenolistnoe (Ipomoea hederacea var. integriuscula), pitted morning glory (Ipomoea lacunosa), field bindweed (Convolvulus arvensis)

weeds of the family Labiatae (Lamiaceae):

purple dead-nettle (Lamium purpureum), dead-nettle (Lamium amplexicaule)

weeds nightshade family (Solanaceae):

jimson weed (Datura stramonium), black nightshade (Solanum nigrum)

weeds of the figwort family (Scrophulariaceae):

Veronica Persian (Veronica persica), Veronica field (Veronica arvensis), Veronica plusline (Veronica hederaefolia)

weeds of the family Asteraceae (Compositae):

the common cocklebur (Xanthium pensilvanicum), annual sunflower (Helianthus annuus), chamomile (Matricaria chamomilla), chamomile nephroma (Matricaria herforata or indora), pineappleweed (Matricaria matricarioides), ragweed polinolistaya (Ambrosia artemisiifolia), ragweed trenatresan (Ambrosia trifida), melkosopochnik canadian (Erigeron canadensis), Japanese wormwood (Artemisia princeps), goldenrod high (Solidago aktissima), common dandelion (Taraxacum officinale)

ornate family spread over:

the forget-me-not (Myosotis arvensis)

weeds of the family Asclepiadaceae:

walochnik Syrian (Asclepias syriaca)

weeds of the family Euphorbiaceae (Euphorbiaceae):

milkweed cancelled (Euphorbia helioscopia), spotted spurge (Euphorbia maculata)

the weeds from the geranium family (Geraniaceae):

the Carolina geranium (Geranium carolinianum)

weeds of the orpine family (Oxalidaceae):

the pink sorrel (Oxalis corymbosa)

weeds gourd family (Cucurbitaceae):

angular cucumber (Sicyos angulatus)

weeds of the family of grasses (Graminaceae):

barnyard grass-plushie millet (Echinochloa crus-galli), spickle green (Setaria viridis), spickle giant (Setaria faberi), weed blood (Digitaria sanguinalis), southern weed (Digitaria ciliaris), Elefsina Indian (Eleusina indica), annual bluegrass (Poa annua), Alopecurus mishegoss-nikolenyi (Alopecurus myosuroides), wild oat (Avena fatua), jonssonova grass (wild sorghum) (Sorghum halpense), couch grass (Agropyron repens), fire roofing (Bromus tectorum), Bermuda grass (cynodon dactylon) (Cenodon dactylon), millet fork (Panicum dichotomiflorum), Texas millet, sorghum ordinary (Sorghum vulgare), Alopecurus crankshaft (Alopecurus geniculatus)

weeds of the family komlinovic (Commelinaceae):

commelina ordinary (Commelina communis)

weeds of the family Equisetaceae:

horsetail (Equisetum arvense)

weeds of the sedge family (Cyperaceae):

syt weerasena (Cyperus iria), chufa purple (Cyperus rotondus), chufa yellow (Cyperus esculentus)

In addition, some of these compounds is not about who make significant phytotoxicity on major crops, such as corn (Zea mays), wheat (Triticum aestivum), barley (Hordeum vulgare), rice (Orysa sativa), sorghum (Sorghum bicolor), soybean (Glycine max), cotton (Gossipium spp.), sugar beet (Beta vulgaris), peanut (Arachis hypogaea), sunflower (Helianthus annuus) and colza (rape (Brassica napus); horticultural crops such as flowers and ornamental plants; and vegetable crops. These compounds can also provide effective protection against a variety of weeds that can cause alarm when no-till cultivation of soybean (Glycine max), corn (Zea mays), wheat (Triticum aestivum) and other crops. In addition, some of these compounds show no significant phytotoxicity on these crops.

These compounds also possess herbicide activity against a variety of weeds that can cause some anxiety when flooding of the rice fields, such as those listed below:

weeds of the family of grasses (Graminaceae):

plushie millet (Echinochloa oryzicola)

weeds of the figwort family (Scrophulariaceae):

common falsepimpernel (Lindernia procumbens)

weeds of the family Grebennikova (Lythraceae):

rotala Indian (Rotala indica), ammannia multifloral (Ammannia multiflora)

weeds of the family Elatinaceae:

povoinik (Elatine triandra)

weeds of the sedge family (Cyperaceae):

melkotsvetnye umbrella sedge (Cyperus difformis), bulrush (Scirpus juncoides), bolotnitsa needle is (Eleocharis acicularis), syt water (Cyperus serotinus), water chestnut (Trapa natans) (Eleocharis kuroguwai)

weeds of the family Pontederiacae:

Monochoria (Monochoria vaginalis)

weeds of the family Alismataceae:

the arrowhead (Sagittaria pygmaea), arrowheads (Sagittaria trifolia), Alisma (Alisma canaliculatum)

weeds of the family Potamogetonaceae:

rotundifolia pondweed (Potamogeton distinctus)

weeds in the Apiaceae (Umbelliferae):

types of omezhnik (Oenanthe javanica)

In addition, some of these compounds show no significant phytotoxicity on seedling rice paddy.

These compounds can also provide protection from a wide variety of weeds that are growing or will grow in orchards, grasslands, lawns, forests, waste channels (waterways), channels, or other uncultivated lands, which need to be protected from weeds, such as a dam, river, road, railway, green space, Park land, Parking (Parking), the airport, the location of industrial enterprises (e.g., plants, equipment for storage), parousia land, vacant land, etc. these compounds also exhibit herbicide activity against various water plants such as water hyacinth (Eichhornia) (Eichhornia crassipes), which are growing or will grow on the banks of water bodies such as rivers, canals, waterways or reservoirs.

These compounds have the t is essentially the same characteristics, that and herbicide compounds described in the published description of the International patent application WO 95/34659. In that case, when cultivated cultivated plants with resistance, communicated to them by the introduction of the gene of resistance to herbicides, these compounds may be used in larger quantities than the number used in the case of the cultivation of conventional crops without such stability, allowing you to more effectively deal with other unwanted weeds.

When using these compounds as active ingredients of herbicides they are usually mixed with solid or liquid carriers or diluents, surfactants and other auxiliary agents to obtain emulsifiable concentrates, wettable powders, flowable wettable powders, granules, concentrated emulsions, dispersible in water granules or other drugs.

These preparations may contain any of these compounds as an active ingredient in a quantity of 0.001 to 80% by weight, preferably 0.005 to 70% by weight calculated on the total weight of the preparation.

Used solid carrier or diluent may include, for example, finely divided powders or granules of the following materials, such as mineral materials, such as kaolin clay, attapulgite clay, b is tonic, acid clay, pyrophyllite, talc, diatomaceous earth and calcite (calcium feldspar); organic substances such as powdered walnut shells; water-soluble organic substances such as urea; inorganic salts such as ammonium sulfate; synthetic hydrated silicon oxide. The liquid carrier or diluent, which may be used may include, for example, aromatic hydrocarbons such as methylnaphthalene, phenylxylylethane and alkylbenzene (e.g., xylene), alcohols, such as isopropanol, ethylene glycol and 2-ethoxyethanol; esters, such as dialkyl ethers phthalic acid; ketones, such as acetone, cyclohexanone and isophorone; mineral oils such as machine oil; vegetable oils such as soybean oil and cottonseed oil; dimethylsulfoxide, N,N-dimethylformamide, acetonitrile, N-organic and water.

Surface-active agent used for emulsification, dispersion or distribution may include surfactants of the anionic type, such as alkyl sulphates, alkyl sulphonates, alkylarylsulphonates, diallylmalonate, and phosphates alkylaryl esters of polyoxy-ethylene; and surfactants of the nonionic type, such as alkalemia esters of polyoxyethylene, alkylacrylate esters of polyoxyethylene, block copolymers is of polyoxyethylene and polyoxypropylene, esters of fatty acids and sorbitan and fatty acid esters of polyoxyethylenesorbitan.

The auxiliary agent may include ligninsulfonate, alginates, polyvinyl alcohol, Arabian gum, CMC (carboxymethylcellulose) and PAP (isopropyl(sour)phosphate)).

These compounds are usually prepared as described above and then used for soil treatment before or after emergence of seedlings, deciduous or irrigation treatment. Soil processing may include processing the soil surface or soil. Deciduous processing may include applying to the plants and sent the application in which the chemical is applied only on the weeds, so as not to affect cultivated plants.

These connections can often be increased herbicide activity when used in mixture with other herbicides. They can also be used in mixture with insecticides, acaricides, nematicides, fungicides, bactericides, plant growth regulators, fertilizers and soil builders (air-conditioned).

Examples of herbicides that can be used in a mixture of these compounds, are atrazine, cyanazine, deltamethrin, metribuzin, prometryn, Simazine, simetryn, chlortoluron, Diuron, fluometuron, Isoproturon, linuron, methabenzthiazuron, propanil, bentazon, bromoxynil, ioxi the sludge, peridot, butamifos, dithiopyr, ethalfluralin, pendimethalin, thiazopyr, trifluralin, acetochlor, alachlor, butachlor, detail-ethyl, dimethenamid, flutamide, mefenacet, metolachlor, pretilachlor, propachlor, cinmetacin, acifluorfen, acifluorfen-sodium, bestindian, bifenox, butoverall, gametocidal, fomesafen, lactofen, oxadiazon, oxadiargyl, oxyfluorfen, carfentrazone-ethyl, flatlet, flumiclorac-pentyl, flumioxazin, fluthiacet-methyl, isopropanol, sulfentrazone, thidiazuron, azafenidin, pyraflufen-ethyl, cinidon-ethyl, difenzoquat, Diquat, paraquat, 2,4-D, 2,4-DB, clopyralid, dicamba, fluroxypyr, MSRA, MSRB, mecoprop, chinkara, triclopyr, azimsulfuron, enculture-methyl, chlorimuron-ethyl, chlorsulfuron, karasulu-methyl, cycloaliphatic, dicloflam, ethoxysulfuron, flazasulfuron, flucarbazone, flumetsulam, flupyrsulfuron, halosulfuron-methyl, imazosulfuron, endosulfan, metosulam, metsulfuron-methyl, nicosulfuron, oxasulfuron, primisulfuron-methyl, procarbazine sodium, prosulfuron, pyrazosulfuron-ethyl, rimsulfuron, sulfometuron-methyl, sulfosulfuron, triasulfuron, tribenuron-methyl, tritosulfuron, thifensulfuron-methyl, triflusulfuron-methyl, perbenzoic, bispyribac sodium, Perminova-methyl, pyrithiobac-sodium, mazamet, imazamethabenz-methyl, imazamox, imazapic, imazapyr, imasa is in, imazethapyr, tepraloxydim, aloxide-sodium, clethodim, clodinafop-propargyl, dehalfop-butyl, diclofop-methyl, fenoxaprop-ethyl, Foxa-prop-p-ethyl, fluazifop-butyl, fluazifop-p-butyl, haloxyfop-methyl, hisamoto-p-ethyl, sethoxydim, tralkoxydim, diflufenican, flurtamone, norflurazon, benzefoam, isoxaflutole, pyrazolate, paradoxien, sulcotrione, clomazone, mesotrione, isoxaflutole, bialaphos, glufosinate-ammonium, glyphosate, sulfosate, dichlobenil, isoxaben, benthiocarb, butyl, timepart, ARTS, asbroker, molinet, perimutter, triallate, bromobutyl, DSMA, MSMA, cafestol, damron, apoprotein, flupoxam, metaventure, phenoxazone, piperophos, triazolam, beflubutamid, benzamycin, clomipram, phentramin, flufenacet, florasulam, indianian, isoxadifen, mesotrione, napleonic, oxacyclobutane, pethoxamid, petiol, perinatol.

The above compound is described in the catalog of Farm Chemical Handbook, 1995 (Meister Publishing Company); AG CHEM NEW COMPOUND REVIEW, VOL.13, 1995, VOL.15, 1997, VOL.16, 1998, or VOL.17, 1999 (AG CHEM INFORMATION SERVICES); or Josoyzai Kenkyu Souran (Hakuyu-sha).

When using these compounds as active ingredients of herbicides applied amount, although it may vary depending on weather conditions, types of drugs, time of application, methods of application, soil conditions, protected crops, subject to eradication of weeds and other the factors is usually in the range of 0.01-20000 g, preferably 1-12000 g per hectare. In the case of emulsifiable concentrates, wettable powders, flowable wettable powders, concentrated emulsions, water-dispersible granules, or other similar drugs, they are usually applied after dilution in prescribed quantities of water (if necessary, containing adjuvant (additive), such as distributing agent) in the ratio of 10-1000 liters per hectare. In the case of granules or certain types of flowable wettable powders, they are usually applied as such without any dilution.

Adjuvants (additives)that can be used, if necessary, may include, in addition to the above-described surfactants, acids (esters) polyoxyethylene resins, ligninsulfonate, abietate, dinaftiletilena, oil concentrates for cultivated plants and vegetable oils such as soybean oil, corn oil, cottonseed oil and sunflower oil.

The following examples of the preparation, sample preparation and sample tests, etc. will be further in detail to illustrate the invention, but they do not limit the scope of the present invention.

First will be shown examples of the preparation of these compounds and examples of the preparation of intermediate products. The number of connections sootvetstvuyuthimi, shown in tables 1-5 below.

Example of getting a 1: getting connection 1-1

of 0.43 g of 4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenol (obtained in example 1 to obtain an intermediate product) is dissolved in 2.0 ml of N,N-dimethylformamide and to the solution was added 0.15 g of anhydrous potassium carbonate and 0.17 g of methyl 2-bromopropionate under stirring at room temperature, then the mixture is stirred for 3 hours at 70°C. the Reaction solution is cooled to room temperature, then the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 0.39 g of methyl 2-[4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydro-pyrimidine-1-yl]phenoxy}phenoxy]propionate [Compound 1-1 of the present invention].

1H-NMR (CDCl3, 300 MHz) δ (ppm): to 1.61 (d, 3H, J=6, 9 Hz), 3,52 (s, 3H), of 3.77 (s, 3H), 4,70 (K, 1H, J=6,7 Hz), of 6.31 (s, 1H), 6,7-6,8 (m, 1H), 6.8 or 6.9 (m, 2H), 6,9-7,0 (m, 2H), was 7.36 (d, 1H, J=9.0 Hz)

Example of receipt 2: receipt of connection 2-1

of 0.30 g of 3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenol (described below, obtained in example 2, obtaining the intermediate p is the FL) dissolved in 1.4 ml of N,N-dimethylformamide and to the solution was added 0.10 g of anhydrous potassium carbonate and 0.11 g of methyl 2-bromopropionate under stirring at room temperature, then this mixture is stirred for 3 hours at 70°C. the Reaction solution is cooled to room temperature, then the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 0.28 g of methyl 2-[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]propionate [Compound 2-1 of the present invention].

1H-NMR (CDCl3, 300 MHz) δ (ppm): 1,60 (d, 3H, J=7.0 Hz), 3,53 (s, 3H), of 3.75 (s, 3H), 4,74 (K, 1H, J=6,7 Hz), 6,32 (s, 1H), 6,5-6,7 (m, 3H), 6,9-7,0 (m, 1H), 7,1-7,3 (m, 1H), 7,38 (d, 1H, J=8,9 Hz)

Example of receipt 3: receipt of connection 3-1

to 0.23 g of 2-{2-chloro-4-fluoro-5-[L-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenol are dissolved in 6 ml N,N-dimethylformamide and to the solution was added to 0.22 g of anhydrous potassium carbonate and 0.13 g of methyl 2-bromopropionate under stirring at room temperature, then the mixture is stirred for 3 hours at 80°C. the Reaction solution is cooled to room temperature, then the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrate the. The residue is subjected to column chromatography on silica gel with getting to 0.23 g of methyl 2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydro-pyrimidine-1-yl]phenoxy}phenoxy]propionate [Compound 3-1 of the present invention].

1H-NMR (CDCl3, 250 MHz) δ (ppm): to 1.47 (d, 3H, J=6.8 Hz), 3,50 (K, 3H, J=0.7 Hz), 3,6-3,8 (m, 3H), 4,6-4,8 (m, 1H), 6,28 (s, 1H), 6,7-6,8 (m, 1H), 6.8 or 6.9 (m, 1H), 6,9-7,1 (m, 1H), 7,1-7,2 (m, 2H), 7.3 to 7.4 (m, 1H)

Physical performance data of the compounds obtained in the same manner as in the example of a 3, shown below.

Ethyl-2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]propionate [Compound 3-2 of the present invention]

1H-NMR (CDCl3, 250 MHz) δ (ppm): of 1.23 (t, 3H, J=7,1 Hz)of 1.47 (d, 3H, J=6,8), 3,50 (s, 3H), 4,1-4,3 (m, 2H), 4,6-4,8 (m, 1H), 6.3 and 6.4 (m, 1H), 6,7-7,0 (m, 3H), 7,0-7,2 (m, 2H), 7.3 to 7.4 (m, 1H)

Methyl-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]acetate [Compound 3-11 of the present invention]

Melting point: 116,4°

Ethyl-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]acetate [Compound 3-12 of the present invention]

1H-NMR (CDCl3, 300 MHz) δ (ppm): 1.26 in (t, 3H, J=7,1 Hz), 3,50 (s, 3H), 4,19 (K, 2H, J=7,2 Hz), with 4.64 (s, 2H), 6,28 (s, 1H), 6,7-6,8 (m, 1H), 6,9-7,2 (m, 4H), of 7.36 (d, 1H, J=8,8 Hz)

Example 4: obtaining connection 3-189

Process 1:

0,365 g of methyl 2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-phenoxy}phenoxy]propionate [Compound 3-1 of the present invention] is dissolved in 4 ml of 1,4-dioxane, the solution was added a mixed solution of 1 ml of concentrated hydrochloric acid and 1 ml of water under stirring, then the mixture is heated for 5 hours and 45 minutes with stirring under conditions of reflux distilled (under reflux). After that, the solution is allowed to cool and the reaction solution was poured ice water, ethyl acetate and added dropwise to this solution, saturated salt solution, which is then separated, and the aqueous solution of sodium bicarbonate is added to the organic layer before separation, the water layer to acidification add aqueous hydrochloric acid, then before the split add ethyl acetate, the organic layer was washed with saturated saline and dried over magnesium sulfate, and then concentrated to obtain 0,183 g 2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionic acid.

1H-NMR (CDCl3, 250 MHz) δ (ppm): 1,53 (d, 3H, J=6.9 Hz), 3,51 (s, 3H), 4,76 of 4.83 (m, 1H), 6,32 (d, 1H, J=3.5 Hz), 6,63 is 6.67 (m, 1H), between 7.0 and 7.1 (m, 2H), 7,1-7,2 (m, 2H), 7,38 (d, 1H, J=9.0 Hz)

Process 2:

2-[2-{2-chloro-4-fluoro-5-[L-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionic acid is dissolved in tetrahydrofuran, to the solution was added thionyl chloride under stirring, then the mixture is heated with stirring under conditions of reflux distilled (under reflux). Then the solution is allowed to cool, concentrated, then dissolved in tetrahydrofuran (hereinafter this solution is called Solution A). The tetrahydrofuran is added to 1-petrovanu alcohol and to this solution add a Solution, then add pyridine. The mixture is stirred at room temperature, then the reaction solution was poured 2% hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over magnesium sulfate, then concentrated. The residue is subjected to column chromatography on silica gel (eluent: hexane/ethyl acetate = 5/1) to obtain pentyl-2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydro-pyrimidine-1-yl]phenoxy}phenoxy]propionate [Compound 3-189 of the present invention].

An example of obtaining 5: getting connection 3-20

Process 1:

0.4 g of methyl-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]acetate [Compound 3-11 of the present invention] is dissolved in 4 ml of 1,4-dioxane, the solution was added a mixed solution of 1 ml of concentrated hydrochloric acid and 1 ml of water under stirring, then the mixture is heated for 12 hours when lane is mesheanii under conditions of reflux distilled (under reflux). After that, the solution is allowed to cool and the reaction solution was poured ice water, ethyl acetate and added dropwise to this solution, saturated salt solution, which is then separated, and the aqueous solution of sodium bicarbonate is added to the organic layer before separation, the water layer to acidification add aqueous hydrochloric acid, then before the split add ethyl acetate, the organic layer was washed with saturated saline and dried over magnesium sulfate, and then concentrated to obtain 0,252 g of [2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetic acid.

1H-NMR (CDCl3, 250 MHz) δ (ppm): 3,50 (d, 3H, J=1.2 Hz), of 4.66 (s, 2H), of 6.31 (s, 1H), 6,69 (d, 1H, J=6.5 Hz), 6,98-7,20 (m, 4H), 7,38 (d, 1H, J=8,8 Hz)

Process 2:

1.0 g of [2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetic acid dissolved in tetrahydrofuran, to the solution was added 0.7 ml of thionyl chloride under stirring, then the mixture is heated with stirring under conditions of reflux distilled for 2 hours under reflux). The solution is allowed to cool, concentrated, then dissolved in 3 ml of tetrahydrofuran (hereinafter this solution is called Solution). 0.7 ml of tetrahydrofuran is added to 0.05 g of allyl alcohol and to this solution is added in the form of three since the second Solution, then add 0,17 ml of pyridine. This mixture is stirred for 2 hours at room temperature, then the reaction solution was poured 2% hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over magnesium sulfate, then concentrated. The residue is subjected to column chromatography on silica gel (eluent: hexane/ethyl acetate = 5/1) to give 0.08 g of the allyl-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]acetate [Compound 3-20 of the present invention].

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,50 (d, 3H, J=1.2 Hz), 4,62 with 4.64 (m, 2H), and 4.68 (s, 2H), 5,22-5,32 (m, 2H), of 5.8-6.0 (m, 1H), 6,28 (s, 1H), 6,76 (d, 1H, J=6.5 Hz), 6,91-7,14 (m, 4H), 7,35 (d, 1H, J=8.6 Hz)

An example of obtaining 6: getting connection 3-16

0.20 g of 2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(tri-permitil)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenol dissolved in 2 ml N,N-dimethylformamide, to the solution was added 0.083 g of potassium carbonate and the mixture was stirred at room temperature for 50 minutes. It adds a 0,077 g of tert-BUTYLCARBAMATE and the mixture is stirred for 2 hours at 40-60°C. After cooling, the reaction solution is poured onto ice water and add ethyl acetate and a saturated saline solution before separation. The organic layer was washed with saturated saline, drying is over magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel (eluent: n-hexane/ethyl acetate = 6/1) to obtain 0.39 g of tert-butyl 2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]acetate [Compound 3-16 of the present invention].

1H-NMR (CDCl3, 250 MHz) δ (ppm): 1,44 (s, N), 3,49 (d, 3H, J=1.1 Hz), a 4.53 (s, 2H), 6,27 (s, 1H), 6,80 (d, 1H, J=6.6 Hz), 6,8-7,2 (m, 4H), 7,35 (d, 1H, J=8,9 Hz)

Melting point: 55,6°

An example of obtaining 7: getting connection 3-198

1.5 g of [2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(tri-permitil)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetic acid dissolved in 6 ml of tetrahydrofuran, to the solution was added 1 ml of thionyl chloride under stirring, then the mixture is heated under stirring and the mixture is stirred for 2 hours and 10 minutes under conditions of reflux distilled (under reflux). Then the solution is allowed to cool, concentrated, then dissolved in 3 ml of tetrahydrofuran (hereinafter this solution is called Solution). 1 ml of tetrahydrofuran is added to 0,273 g of isobutyl alcohol and to this solution was added in three portions to the Solution, then add 0.25 ml of pyridine. After that, the mixture is stirred for 2 hours at room temperature, then the reaction solution was poured 2% hydrochloric acid and add ethyl acetate before separation, the organic layer industry is saturated with brine and dried over magnesium sulfate, then concentrate. The residue is subjected to column chromatography on silica gel (eluent: hexane/ethyl acetate = 6/1) to give 0.34 g of isobutyl-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]acetate [Compound 3-198 of the present invention].

1H-NMR (CDCl3, 250 MHz) δ (ppm): 0,89 (d, 6N, J=6,7 Hz), 1,8-2,0 (m, 1H), 3,50 (d, 3H, J=1.2 Hz), 3,92 (d, 2H, J=6,7 Hz), of 4.67 (s, 2H), 6,28 (s, 1H), 6,77 (d, 1H, J=6, 6 Hz), 6,85-to 7.15 (m, 4H), of 7.36 (d, 1H, J=8,9 Hz)

An example of obtaining 8: getting connection 3-11

To 0,93 g of methyl-[2-{2-chloro-4-fluoro-5-[2, 6-dioxo-4-(trifter-methyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fervency}phenoxy]acetate add 10 ml of N,N-dimethylformamide and 0.31 g of potassium carbonate, and then to the reaction solution was added 0,58 g under the conditions and the mixture is stirred at room temperature for 2 hours. To the reaction solution add 50 ml of diluted hydrochloric acid and extracted with ethyl acetate. The organic layer is washed with water and then brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is subjected to column chromatography on silica gel with receipt of 0.82 g of methyl-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]-acetate [Compound 3-11 of the present invention].

1H-NMR (CDCl3, 250 MHz) δ (ppm): 3,493,50 (m, 3H), of 3.73 (s, 3H), of 4.66 (s, 2H), 6,28 (s, 1H), 6,76 (d, 1H, J=6, 6 Hz), 6,9-7,2 (m, 4H), of 7.36 (d, 1H, J=8,9 Hz)

An example of obtaining 9: getting connection 3-12

To ethyl-[2-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate is added N,N-dimethylformamide and potassium carbonate, and then to this reaction solution add methyliodide and the mixture is stirred at room temperature. To the reaction solution add dilute hydrochloric acid and extracted with ethyl acetate. The organic layer is washed with water and then saturated saline and dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain ethyl-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydro-pyrimidine-1-yl]phenoxy}phenoxy]acetate [Compound 3-12 of the present invention].

Example 10: the connection 1-2

100 mg of 4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenol (obtained in example 1 to obtain an intermediate product) is dissolved in 1.0 ml of N,N-dimethylformamide and to the solution was added 42 mg of anhydrous potassium carbonate and 46 mg of ethyl-2-bromopropionate under stirring at room temperature, then the mixture is stirred for 2 hours at 60°C.

The reaction solution is cooled to room for the Noah temperature, then the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 85 mg of ethyl-2-[4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydro-pyrimidine-1-yl]phenoxy}phenoxy]propionate [Compound 1-2 of the present invention].

1H-NMR (CDCl3, 300 MHz) δ (ppm): of 1.27 (t, 3H, J=7.0 Hz), 1,60 (d, 3H, J=6.9 Hz), 3,52 (s, 3H), 4,23 (K, 2H, J=7.0 Hz), 4,68 (K, 1H, J=6.9 Hz), of 6.31 (s, 1H), 6,7-6,8 (m, 1H), 6.8 or 6.9 (m, 2H), 6,9-7,0 (m, 2H), 7,37 (d, 1H, J=8,9 Hz)

An example of obtaining 11: obtain compounds 1-11

150 mg of 4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenol (described below obtained in example 1 to obtain an intermediate product) is dissolved in 1.0 ml of N,N-dimethylformamide and to the solution was added 51 mg of anhydrous potassium carbonate and 50 mg of methylpropanoate under stirring at room temperature, then the mixture is stirred for 2 hours at 60°C. the Reaction solution is cooled to room temperature, then the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The remainder powergallery chromatography on silica gel to obtain 167 mg of methyl-[4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]acetate [Compound 1-11 of the present invention].

1H-NMR (CDCl3, 250 MHz) δ (ppm): 3,52 (K, 3H, J=1.1 Hz), 3,81 (s, 3H), to 4.62 (s, 2H), 6,32 (s, 1H), 6,74 (d, 1H, J=6.6 Hz), 6.8 or 6.9 (m, 2H), 6,9-7,0 (m, 2H), 7,37 (d, 1H, J=8,9 Hz)

Example 12: the connection 2-11

100 mg of 3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenol (described below, obtained in example 2 to obtain intermediate products) dissolved in 1 ml N,N-dimethylformamide and to the solution was added 34 mg of anhydrous potassium carbonate and 37 mg of methylpropanoate under stirring at room temperature, then the mixture is stirred for 1 hour at 60°C. the Reaction solution is cooled to room temperature, then the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 110 mg of methyl-[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]-acetate [Compound 2-11 of the present invention].

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,53 (K, 3H, J=0.9 Hz), 3,80 (s, 3H), br4.61(s, 2H), 6,32 (s, 1H), 6,60 (s, 1H), 6,6-6,7 (m, 2H), 6,92 (d, 1H, J=6.6 Hz), of 7.23 (d, 1H, J=7.9 Hz), 7,39 (d, 1H, J=9.0 Hz)

An example of obtaining 13: getting connection 5-7

72 mg of 3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(triform the Teal)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenol (described below obtained in example 9 to obtain the intermediate product) is dissolved in 1.0 ml of N,N-dimethylformamide and to the solution was added 31 mg of anhydrous potassium carbonate and 31 mg of methyl 2-bromopropionate under stirring at room temperature, then the mixture is stirred for 1 hour at 70°C. the Reaction solution is cooled to room temperature, then the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel with 80 mg of methyl 2-[3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifter-methyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate [Compound 5-7 of the present invention].

1H-NMR (CDCl3, 250 MHz) δ (ppm): of 1.62 (d, 3H, J=6.8 Hz), 3,53 (K, 3H, J=1.4 Hz), of 3.77 (s, 3H), 4.75 in (K, 1H, J=6,8 Hz), and 6.3-6.4 (m, 1H), 6,6-6,8 (m, 3H), 6.8 or 6.9 (m, 1H), 7,2-7,3 (m, 1H), 7,53 (d, 1H, J=8.4 and Hz)

An example of obtaining 14: getting connection 5-22

32 mg of 3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenol (described below, obtained in example 9 to obtain the intermediate product) is dissolved in 0.5 ml of acetonitrile and to this solution was added 13 mg of methylpropanoate and 13 mg of anhydrous potassium carbonate, and then the mixture is stirred for 1.5 h the sa at 60° C. the Reaction solution is cooled to room temperature, then the reaction solution is subjected to column chromatography on silica gel to obtain 26 mg of methyl-[3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]acetate [Compound 5-22 of the present invention].

1H-H-NMR (CDCl3, 300 MHz) δ (ppm): 3,53 (K, 3H, J=1.0 Hz), 3,81 (s, 3H), 4,63 (s, 2H), 6,32 (s, 1H), and 6.6 and 6.7 (m, 1H), 6,7-6,8 (m, 2H), 6,85 (d, 1H, J=5,9 Hz), 7,2-7,4 (m, 1H), 7,54 (d, 1H, J=8,4 Hz)

An example of obtaining 15: getting connection 4-9

The mixture 15,16 g of 2-(methoxycarbonyl)methoxyphenol, 29,23 g 2,5-debtor-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene (obtained in example 4 to obtain intermediate products), and 11.5 g of anhydrous potassium carbonate and 160 ml of N,N-dimethylformamide was stirred at room temperature for 30 minutes and then stirred at 70°C for 3 hours. To this mixture is added 5 g of 2-(methoxycarbonyl)methoxyphenol and stirred for 1 hour. The reaction solution was poured into 2% aqueous hydrochloric acid solution and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 17.8 g of 2-{2-(methoxycarbonyl)methoxyphenoxy}-5-fluoro-4-[3-methyl-2, dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene [Join 4-19 of the present invention].

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,50 (K, 3H, J=1.0 Hz), 3,70 (s, 3H), 4,63 (s, 2H), 6,28 (s, 1H), to 6.88 (d, 1H, J=8,4 Hz), 6,93 (d, 1H, J=6.0 Hz), to 7.0, and 7.1 (m, 1H), 7,1-7,3 (m, 2H), 7,87 (d, 1H, J=8.7 Hz)

Example 16: the connection 3-11 of this invention

The mixture 11,02 g isoamylamine and 45 ml of acetonitrile is added dropwise to the mixture 15,16 g 5-fluoro-2-{2-(methoxycarbonyl)methoxyphenoxy}-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline (obtained in example 10 to obtain intermediate products), 6,21 g of copper chloride (I), 12,65 g of copper chloride (II) and 250 ml of acetonitrile at room temperature and the mixture is stirred for 2 hours. This reaction solution was poured into 2% hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 13 g of methyl-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate [Compound 3-11 of the present invention].

An example of obtaining 17: getting connection 4-20

this invention

Methyl-[2-{2,4-debtor-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]-acetate [Compound 4-20 of the present invention] is obtained from 5-fluoro-2-{2-(methoxycarbonyl)methoxyphenols the}-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-aniline (obtained in example 10 to obtain intermediate products) according to the method of example 16.

1H-NMR (CDCl3, 250 MHz) δ (ppm): to 3.52 (s, 3H), and 3.72 (s, 3H), with 4.64 (s, 2H), 6,32 (s, 1H), 6,8-7,2 (m, 6N)

An example of obtaining 18: getting connection 4-21 of this invention

Methyl-[2-{2-bromo-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]acetate [Compound 4-21 of the present invention] is obtained from 5-fluoro-2-{2-(methoxycarbonyl)methoxyphenoxy}-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-aniline (obtained in example 10 to obtain an intermediate products) according to the method of example 16.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,53 (K, 3H, J=1.0 Hz), and 3.72 (s, 3H)and 4.65 (s, 2H), 6,33 (s, 1H), 6,72 (d, 1H, J=6.4 Hz), 6,8-7,2 (m, 4H), 7,53 (d, 1H, J=8.6 Hz)

An example of obtaining 19: obtaining connection 4-22 Methyl-[2-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(tri-permitil)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy-acetate [Compound 4-22 of the present invention] is obtained from methyl [2-{2-bromo-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]acetate [Compound 4-21] according to the 4th process of example 9 to obtain the intermediate product described below.

1H-NMR (CDCl3, 250 MHz) δ (ppm): 3,49 (K, 3H, J=0.8 Hz), 3,71 (s, 3H), 4,63 (s, 2H), 6,27 (s, 1H), 6,79 (d, 1H, J=5.8 Hz), 6.87 in (d, 1H, J=8.1 Hz), to 7.0, and 7.1 (m, 1H), 7,1-7,3 (m, 2H), 7,49 (d, 1H, J=8,4 Hz)

Example 1 obtaining intermediate products: Obtain 4-{2-chloro-4-fluoro-5-[3-methyl-2,6-is ioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol

The first method is:

The mixture 1,71 g of 4-benzyloxyphenol and 4.0 ml of N,N-dimethylformamide is added dropwise to a mixture of 0.34 g of sodium hydride and 8.5 ml of N,N-dimethylformamide under ice cooling, and the mixture is stirred for 20 minutes. A mixture of 3.0 g of 2,5-debtor-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene (described below obtained in Example 4 to obtain intermediate products) and 7.0 ml of N,N-dimethylformamide is added dropwise at the same temperature and stirred for 1 hour. The reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer is washed once with 1 n hydrochloric acid and once with saturated saline and dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 2.0 g of 2-(4-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.

1H-NMR (CDCl3, 250 MHz) δ (ppm): 3,51 (K, 3H, J=1.2 Hz), 5,04 (s, 2H), of 6.31 (s, 1H), 6.87 in (d, 1H, J=5,9 Hz), 6,9-7,1 (m, 4H), 7.3 to 7.5 (m, 5H), to 7.84 (d, 1H, J=8.6 Hz)

The second method is:

To a mixture of 2.0 g of iron powder, 6 ml of acetic acid and 0.6 ml of water is added dropwise a solution of 1.9 g of 2-(4-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene in 5.0 ml of acetic acid at podderjana the temperature of the reaction solution at 35° C or lower. After complete addition, the mixture is stirred for 2 hours, then the reaction solution is filtered through celite and diluted with ethyl acetate. The mixture is neutralized with saturated aqueous sodium bicarbonate solution, the organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated, and the resulting residue is subjected to column chromatography on silica gel to obtain 1.0 g of 2-(4-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline.

1H-NMR (CDCl3, 250 MHz) δ (ppm): 3,51 (K, 3H, J=1.3 Hz), 5,02 (s, 2H), 6.30-in (s, 1H), return of 6.58 (d, 1H, J=6, 9 Hz), 6,62 (d, 1H, J=10,8 Hz), 7.3 to 7.5 (m, 5H)

The third way:

0,46 g soliditet added dropwise to a mixture of 1.0 g of 2-(4-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline, 0,38 g of copper chloride (I), 0,78 g of copper chloride (II) and 14 ml of acetonitrile at room temperature and the mixture is stirred for 1 hour. The reaction solution was poured into 2% hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 0.73 g ([4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifter-methyl)-1,2,3,6-tetrahydropyrimidin-1-the l]phenoxy}-phenoxy]-methyl)benzene.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,51 (s, 3H), of 5.03 (s, 2H), 6.30-in (s, 1H), 6,74 (d, 1H, J=6.5 Hz), the 6.9 to 7.0 (m, 4H), 7,2-7,5 (m, 6N)

The fourth way:

To 0,72 g ([4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]methyl)benzene is added 2 ml of ethyl acetate, 0.7 ml of ethanol and 36 mg of 10% palladium on coal and the mixture is stirred for 5 hours at room temperature in a hydrogen atmosphere. The reaction system is rinsed with nitrogen, then the reaction solution is filtered through celite, the filtrate concentrated with the receipt of 0.48 g of 4-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenol.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,51 (s, 3H), 5,2-5,5 (W, 1H), 6.30-in (s, 1H), 6,6-7,0 (m, 5H), was 7.36 (d, 1H, J=9.0 Hz)

Example 2 obtain intermediate products: Obtain 3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol

The first method is:

The mixture 1,71 g 3-benzyloxyphenol and 4.0 ml of N,N-dimethylformamide is added dropwise to a mixture of 0.34 g of sodium hydride and 8.5 ml of N,N-dimethylformamide under ice cooling, and the mixture is stirred for 20 minutes. A mixture of 3.0 g of 2,5-debtor-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene (described below obtained in Example 4 to obtain intermediate products) and 7.0 ml of N,N-dimethylformamide was added drop is at the same temperature and stirred for 1 hour. The reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer is washed once with 1 n hydrochloric acid and once with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 2.4 g of 2-(3-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,53 (K, 3H, J=1.2 Hz), to 5.03 (s, 2H), 6,33 (s, 1H), and 6.6 and 6.7 (m, 1H), 6,7-6,8 (m, 1H), 6.8 or 6.9 (m, 1H), 7,01 (d, 1H, J=6,1 Hz), 7,2-7,5 (m, 4H), 7,87 (d, 1H, J=8.6 Hz)

The second method is:

To a mixture of 2.5 g of iron powder, 8 ml of acetic acid and 0.8 ml of water is added dropwise a solution of 2.4 g of 2-(3-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifter-methyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene in 6.0 ml of acetic acid while maintaining the temperature of the reaction solution at 35°With or below. After complete addition, the mixture is stirred for 2 hours, then the reaction solution is filtered through celite and diluted with ethyl acetate. The mixture is neutralized with saturated aqueous sodium bicarbonate solution, the organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated, and the resulting residue is subjected to column chromatography on silica gel with getting a 1.5 G2-(3-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline.

Melting point: 67,0°

The third way:

0.34 g of isoamylamine added dropwise to a mixture of 1.5 g of 2-(3-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline, or 0.57 g of copper chloride (I), 1,17 g of copper chloride (II) and 21 ml of acetonitrile at room temperature and the mixture is stirred for 1 hour. The reaction solution was poured into 2% hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 1.01 g ([3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifter-methyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]methyl)-benzene.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,53 (K, 3H, J=0.9 Hz), to 5.03 (s, 2H), 6,33 (s, 1H), 6,6-6,7 (m, 2H), 6,7-6,8 (m, 1H), 6,92 (d, 1H, J=6.5 Hz), 7,2-7,5 (m, 7H)

The fourth way:

To 1.01 g ([3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]methyl)benzene add 3 ml of ethyl acetate, 1 ml of ethanol and 50 mg of 10% palladium on coal and the mixture is stirred for 5 hours at room temperature in a hydrogen atmosphere. The reaction system is rinsed with nitrogen, then the reaction solution is filtered through celite, the filtrate is concentrated to obtain 0.68 g of 3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(tripto is methyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenol.

1H-NMR (CDCl3, 300 MHz) δ (ppm): to 3.52 (s, 3H), 5,5-5,8 (W, 2H), 6,32 (s, 1H), 6,4-6,5 (m, 1H), 6,5-6,6 (m, 2H), 6,93 (d, 1H, J=6,7 Hz), 7,17 (DD, 1H, J=8,3 Hz, 7.9 Hz), 7,38 (d, 1H, J=9.0 Hz)

Example 3 to obtain intermediate products: Obtain 2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol

The first method is:

A mixture of 4.05 g of 2-benzyloxyphenol and 9.5 ml of N,N-dimethylformamide is added dropwise to a mixture of 0.80 g of sodium hydride and 20 ml of N,N-dimethylformamide under ice cooling, and the mixture is stirred for 30 minutes. A mixture of 7.1 g of 2,5-debtor-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene (described below obtained in Example 4 to obtain intermediate products) and 17 ml of N,N-dimethylformamide is added dropwise at the same temperature and stirred for 1 hour. The reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer is washed once with 1 n hydrochloric acid and once with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 8.6 g of 2-(2-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.

1H-NMR (CDCl3, 250 MHz) δ (ppm): 3,52 (K, 3H, J=1.1 Hz), free 5.01 (s, 2H), of 6.31 (s, 1H), for 6.81 (d, 1H, J=6.0 Hz), ,9-7,1 (m, 2H), and 7.1 to 7.4 (m, 7H), 7,78 (d, 1H, J=8.7 Hz)

The second method is:

To a mixture of 8.6 g of iron powder, 27 ml of acetic acid and 2.7 ml of water is added dropwise a solution of 8.6 g of 2-(2-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifter-methyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene in 23 ml of acetic acid while maintaining the temperature of the reaction solution at 35°With or below. After complete addition, the mixture is stirred for 2 hours, then the reaction solution is filtered through celite and diluted with ethyl acetate. The mixture is neutralized with saturated aqueous sodium bicarbonate solution, the organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated, and the resulting residue is subjected to column chromatography on silica gel with getting 6,46 g 2-(2-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline.

1H-NMR (CDCl3, 250 MHz) δ (ppm): 3,50 (K, 3H, J=1.2 Hz), is 5.06 (s, 2H), 6,29 (s, 1H), to 6.57 (DD, 1H, J=8,5 Hz, 1.6 Hz), the 6.9 to 7.0 (m, 1H), between 7.0 and 7.1 (m, 3H), 7,2-7,4 (m, 6N)

The third way:

4,46 g soliditet added dropwise to the mixture 6,46 g 2-(2-benzyloxyphenyl)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline, of 2.45 g of copper chloride (I), 5,04 g of copper chloride (II) and 90 ml of acetonitrile at room temperature and the mixture is stirred for 1 hour. The reaction the solution was poured into 2% hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 4.6 g ([2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]methyl)-benzene.

Melting point: 50,8°

The fourth way:

To 4.5 g ([2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-phenoxy]methyl)benzene added 230 ml of ethyl acetate and 0.46 g of 10% palladium on coal and the mixture is stirred for 5 hours at room temperature in a hydrogen atmosphere. The reaction system is rinsed with nitrogen, then the reaction solution is filtered through celite, the filtrate is concentrated to obtain 3.57 g of 2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol.

Melting point: 55,4°

Example 4 obtaining intermediates 4: Getting 2.5-debtor-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene

1,77 g 2,4,5-cryptomaterial and of 1.94 g of 3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidine dissolved in 10 ml of dimethylsulfoxide and the solution was added 1.52 g of anhydrous potassium carbonate at room temperature, then the mixture is stirred for 1 hour at 80°C. the Reaction solution autostate to room temperature, then the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 1.51 g of 2,5-debtor-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-nitrobenzene.

Melting point: 150°

Example 5 to obtain intermediate products: Obtain methyl-[2-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate

The first method is:

2,73 g of 2-methoxyphenol and 5.5 g of potassium carbonate are added to 20 ml of N,N-dimethylformamide and the mixture is heated to 60°C. To this mixture is added dropwise a solution containing 4.3 g of N-(2,5-debtor-4-nitrophenyl)ndimethylacetamide and 30 ml of N,N-dimethylformamide at a temperature from 60 to 65°C. This temperature of the mixture is maintained for 1 hour under stirring, then the mixture is cooled to room temperature, poured into water, extracted with ethyl acetate and the organic layer washed with diluted hydrochloric acid, washed with water, dried over magnesium sulfate and concentrated to obtain 5,52 g of N-[2-fluoro-5-(2-methoxyphenoxy)-4-nitrophenyl]ndimethylacetamide.

1H-NMR (CDCl3, 250 MHz) δ (ppm): of 2.16 (3H, s), of 3.78 (3H, s), 6,85-7,22 (4H, m), 7,75-7,83 (1H, Shir), 7,83 (1H, d, J=10,7 Hz), of 8.04 (1H, d, J=6,9 Hz)/p>

The second method is:

to 5.4 g of N-[2-fluoro-5-(2-methoxyphenoxy)-4-nitrophenyl]-ndimethylacetamide dissolved in 50 mol of methylene chloride, were then added 4.7 g of tribromide boron under ice cooling. The mixture is stirred for 2 hours at the same temperature, added to a solution of concentrated hydrochloric acid and the resulting mixture is poured into water, extracted with ethyl acetate, the organic layer washed with water, dried over magnesium sulfate, concentrated and the resulting crystals are washed with tert-butylmethylamine ether to obtain 3.2 g of N-[2-fluoro-5-(2-hydroxyphenoxy)-4-nitrophenyl]ndimethylacetamide.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 2,20 (3H, s), 6,33 (1H, Sirs), 6,86-of 7.23 (4H, m), 7,63 (1H, Sirs), 7,81 (1H, d, J=10.3 Hz), a 8.34 (1H, d, J=6,7 Hz)

The third way:

to 3.02 g of N-[2-fluoro-5-(2-hydroxyphenoxy)-4-nitrophenyl]-ndimethylacetamide dissolved in 20 ml of N,N-dimethylformamide, then add 1.5 g of potassium carbonate and the mixture is stirred for 1 hour at room temperature. Then add 1.6 g of methylpropanoate at room temperature. The mixture is stirred for 2 hours under the same conditions, poured into water, extracted with ethyl acetate and the organic layer washed with diluted hydrochloric acid, then with water, dried over magnesium sulfate, concentrated and the resulting crystals are washed with tert-butylmethylamine ether with obtaining a 3.01 g of methyl-[2-(5-acetyl what Mino-4-fluoro-2-nitrophenoxy)phenoxy]acetate.

1H-NMR (CDCl3, 250 MHz) δ (ppm): of 2.16 (3H, s), of 3.73 (3H, s), to 4.62 (2H, s), 6,95-7,26 (4H, m), 7,71 (1H, Sirs), a 7.85 (1H, d, J=10,7 Hz), of 8.06 (1H, d, J=6,9 Hz)

The fourth way:

In a mixture of 40 ml of acetic acid and 40 ml of water is added 2.2 g of iron powder and the mixture is heated to 80°C. the mixture was added 3.0 g of methyl-[2-(5-acetylamino-4-fluoro-2-nitrophenoxy)phenoxy]acetate and the mixture is heated for 30 minutes under reflux with reflux distilled. After that, the mixture was poured into water, extracted with ethyl acetate, the organic layer washed with water, then saturated aqueous sodium bicarbonate, dried over magnesium sulfate and concentrated to obtain a 2.01 g of methyl-[2-(5-acetylamino-2-amino-4-pertenece)phenoxy]acetate.

1H-NMR (CDCl3, 250 MHz) δ (ppm): 2,11 (3H, s), 3,31-to 4.15 (2H, Sirs), 3,76 (3H, s), 4,71 (2H, s), is 6.54 (1H, d, J=11,9 Hz), 6.90 to-7,01 (4H, m), 7,17 (1H, Sirs), of 7.69 (1H, d, J=7,54 Hz)

The fifth way:

To 30 ml of concentrated hydrochloric acid is added 2.0 g of methyl-[2-(5-acetylamino-2-amino-4-pertenece)phenoxy]acetate and the mixture is stirred for 1 hour at room temperature. Then add a mixture of 0.42 g of sodium nitrite and 3 ml of water while cooling with ice. The mixture is stirred for 1 hour under the same conditions, then add 40 ml tert-butyl methyl ether, then add to 0.85 g of copper chloride (I). The mixture is stirred for 30 minutes, then dobavlaut water and extracted with tert-butylmethylamine ether and the organic layer washed with water, dried over magnesium sulfate and concentrated and the resulting residue is purified column chromatography (eluent: hexane/ethyl acetate = 2/1) to obtain 0.52 g of methyl-[2-(5-acetylamino-2-chloro-4-pertenece)phenoxy]acetate.

Melting point: 138,9°

Sixth way:

A 10 ml solution in methanol complex of boron TRIFLUORIDE - methanol add 0.25 g of methyl-[2-(5-acetylamino-2-chloro-4-fluoro-phenoxy)phenoxy]acetate and the mixture is heated for 3 hours under stirring. After that, the reaction solution is concentrated and the residue is dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate and concentrated to obtain 0.2 g of methyl-[2-(5-amino-2-chloro-4-pertenece)phenoxy]acetate [Intermediate compounds A3-22].

1H-NMR (CDCl3, 250 MHz) δ (ppm): 3,74 ((3H, s), 3,86 (2H, Sirs), 4,70 (2H, s), 6,36 (1H, d, J=8,21 Hz), 6,83-to 7.09 (5H, m)

The seventh way:

In a mixture of methyl-[2-(5-amino-2-chloro-4-pertenece)-phenoxy]acetate [Intermediate compounds A3-22], methyl-chloroformate and tetrahydrofuran is added dropwise pyridine and the mixture is stirred at room temperature. To the reaction solution add dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated to obtain meth is l-[2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenyl)phenoxy]acetate [Intermediate compound A9-22].

The eighth way:

To ethyl-3-amino-4,4,4-trifurcation add N,N-dimethylformamide and sodium hydride and the mixture is stirred at 0°C. thereafter, to the reaction solution was added a mixture of methyl-[2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenyl)phenoxy]acetate [Intermediate compound A9-22] and N,N-dimethylformamide and the mixture is stirred at 80°C. Then the reaction solution is cooled to room temperature, then poured into a mixture of hydrochloric acid and ice water and the precipitated the crystals are collected by filtration to obtain methyl-[2-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate. Example 6 to obtain intermediate products: obtain ethyl-[2-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate

The first method is:

1.1 g of catechin and 2.76 g of potassium carbonate are added to 20 ml of N,N-dimethylformamide and the mixture is heated to 60°C. To this mixture is added dropwise a solution containing 2.16 g of N-(2,5-debtor-4-nitrophenyl)ndimethylacetamide and 10 ml of N,N-dimethylformamide at temperatures from 65 to 70°C. This temperature of the mixture is maintained for 1 hour, then the mixture is cooled to room temperature, poured into water, extracted with ethyl acetate and the organic layer washed with diluted hydrochloric acid, then water, dried over with what LifeCam magnesium, concentrated and the resulting crystals are washed with tert-butylmethylamine ether with the receipt of 2.56 g of N-[2-fluoro-5-(2-hydroxyphenoxy)-4-nitrophenyl]ndimethylacetamide.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 2,20 (3H, s), 6,33 (1H, Sirs), 6,86-of 7.23 (4H, m), 7,63 (1H, Sirs), 7,81 (1H, d, J=10.3 Hz), a 8.34 (1H, d, J=6,7 Hz)

The second method is:

In a mixture of 25 ml of acetic acid and 25 ml of water is added 9.5 g of iron powder and the mixture is heated to 80°C. To this mixture is added dropwise a solution consisting of 10.0 g of N-[2-fluoro-5-(2-hydroxyphenoxy)-4-nitrophenyl]ndimethylacetamide and 100 ml of ethyl acetate. The mixture is heated for 1 hour under reflux, then poured into water, extracted with ethyl acetate, the organic layer washed with water and washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate and concentrated to obtain 7,42 g of N-[4-amino-2-fluoro-5-(2-hydroxyphenoxy)phenyl]ndimethylacetamide.

1H-NMR (CDCl3, 250 MHz) δ (ppm): of 2.16 (3H, s), 6.48 in (1H, d, J=11,6 Hz), 6,74-of 6.78 (2H, m), 6,93-of 6.96 (2H, m), 7,35 (1H, Sirs), 7,47 (1H, d, J=7,4 Hz)

The third way;

of 7.4 g of N-[4-amino-2-fluoro-5-(2-hydroxyphenoxy)phenyl]-ndimethylacetamide dissolved in 30 ml of acetonitrile, then add 5,42 g of copper chloride (II) and the mixture is stirred at room temperature. Thereto is added dropwise a solution consisting of 4,16 g of tert-butylnitrite and 5 ml of acetonitrile at about room temperature. The mixture is stirred during the 1 hour at room temperature, then poured into water, extracted with ethyl acetate, the organic layer is washed with diluted hydrochloric acid, then with water, dried over magnesium sulfate, concentrated and the resulting residue is purified column chromatography on silica gel (eluent: GEK-San/ethyl acetate = 2/1) to give to 3.92 g of N-[4-chloro-2-fluoro-5-(2-hydroxyphenoxy)phenyl]ndimethylacetamide.

1H-NMR (CDCl3, 250 MHz) δ (ppm): 2,19 (3H, s)5,72 (1H, s)6,70-6,84 (2H, m), 7,01-7,02 (2H, m), 7.23 percent (1H, d, J=10.3 Hz), 7,34 (1H, Sirs), 8,18 (1H, d, J=7,4 Hz)

The fourth way:

N-[4-chloro-2-fluoro-5-(2-hydroxyphenoxy)phenyl]ndimethylacetamide dissolved in N,N-dimethylformamide, then add the potassium carbonate and the mixture is stirred at room temperature. Then add ethylbromoacetate at room temperature. The mixture was stirred at the same temperature, poured into water, extracted with ethyl acetate, the organic layer is washed with diluted hydrochloric acid, washed with water, dried over anhydrous magnesium sulfate and concentrated and the resulting crystals are washed with tert-butylmethylamine ether to obtain ethyl-[2-(5-acetylamino-2-chloro-4-pertenece)-phenoxy]acetate.

The fifth way:

In solution in methanol complex of boron TRIFLUORIDE-methanol add ethyl-[2-(5-acetylamino-2-chloro-4-pertenece)phenoxy]acetate and this mixture is heated with stirring. After that, the reaction solution will contentresult, the residue is dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate and concentrated to obtain ethyl-[2-(5-amino-2-chloro-4-pertenece)phenoxy]-acetate [Intermediate compounds A3-23].

Sixth way:

In a mixture of ethyl-[2-(5-amino-2-chloro-4-pertenece)phenoxy] acetate [Intermediate compounds A3-23], ethylchloride and tetrahydrofuran is added dropwise pyridine and the mixture is stirred at room temperature. To the reaction solution add dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated to obtain ethyl-[2-(2-chloro-4-fluoro-5-ethoxycarbonylmethoxy)phenoxy]acetate [Intermediate compound A8-23].

The seventh way:

To ethyl-3-amino-4,4,4-trifurcation add N,N-dimethylformamide and sodium hydride and the mixture is stirred at 0°C. thereafter, to the reaction solution was added a mixture of ethyl-[2-(2-chloro-4-fluoro-5-ethoxycarbonylmethoxy)phenoxy]acetate [Intermediate compound A8-23] and N,N-dimethylformamide and the mixture is stirred at 80°C. Then the reaction solution is cooled to room temperature, then poured into a mixture of hydrochloric acid and ice water and saducees crystals collect filter is a W with obtaining ethyl-[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2, 3,6-those t-rehydrogenation-1-yl]-4-fervency}phenoxy]acetate.

Example 7 to obtain intermediate products: Obtain ethyl-[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fervency}phenoxy]acetate

The first method is:

In a mixture of ethyl-[2-(5-amino-2-chloro-4-pertenece)phenoxy]-acetate [Intermediate compounds A3-23], trichloromethylcarbonate and toluene is added dropwise activated charcoal and the mixture is heated at reflux distilled. The reaction solution is filtered and the solvent is distilled off to obtain 4-chloro-2-fluoro-5-{2-(ethoxycarbonylmethoxy)phenoxy}-phenylisocyanate [Intermediate A12-23].

The second method is:

To ethyl-3-amino-4,4,4-trifurcation add N,N-dimethylformamide and sodium hydride and the mixture is stirred at 0°C. thereafter, to the reaction solution was added a mixture of 4-chloro-2-fluoro-5-{2-(ethoxycarbonylmethoxy)phenoxy}phenylisocyanate [Intermediate A12-23] and N,N-dimethylformamide and the mixture is stirred at room temperature. The reaction solution is poured into a mixture of hydrochloric acid and ice water and saducees crystals are collected by filtration to obtain ethyl-[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fervency}phenoxy]acetate.

Example 8 to obtain intermediate products: Obtain methyl-[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,6-tetrahydropyrimidin-1-yl]-4-fervency}phenoxy]acetate

The first way: Getting connection [2h] from compound [1h]

A solution consisting of 4,85 g of compound [1h], 2,88 g ethyltrichlorosilane and 40 ml of toluene, and subjected to azeotropic reaction with removal of ethanol by passing through a molecular sieve 5A for 6 hours. After cooling, 50 ml of ethyl acetate is added to the reaction mixture, then the organic layer was washed with concentrated hydrochloric acid, water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was washed with hexane to obtain of 5.82 g of the crude compound [2h].

Melting point: 165,3°

The second way to Obtain compound [3h] from compound [2h]

To a solution of 1.0 g of the crude compound [2h] and 3 ml of tetrahydrofuran, add 4 ml of acetic acid and 0.87 g of potassium cyanate and the mixture is stirred at room temperature for 6 hours, then heated under reflux at 120°C for 2 hours. After cooling, to the reaction mixture are added water (30 ml) and the mixture extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, water and saturated saline and then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is subjected to column chromatography the raffia on silica gel with receipt of 0.67 g of compound [3h].

1H-NMR (CDCl3, 250 MHz) δ (ppm): and 3.72 (3H, s)and 4.65 (2H, s), 6,16 (1H, s), 6,77 (1H, d, J=6.6 Hz), 6.89 in-to 7.15 (4H, m), of 7.36 (1H, d, J=8,9 Hz)

Ethyl-[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fervency}phenoxy]acetate obtained from ethyl-[2-(5-amino-2-chloro-4-pertenece)phenoxy]-acetate [Intermediate compounds A3-23] in accordance with the process of Example 8 to obtain intermediate products.

Example 9 to obtain the intermediate products: Obtain 3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol

The first method is:

A mixture of 3.53 g of 3-methoxyphenol, 5,12 g of anhydrous potassium carbonate, 10 g of 2,5-debtor-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene (described above, obtained in Example 4 to obtain intermediate products) and 40 ml of N,N-dimethylformamide was stirred at 60-70°C for 2 hours. The reaction mixture was poured into a mixture of aqueous hydrochloric acid and ice water and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel with receipt of 4.17 g of 5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.

1H-NMR (CDCl3, 250 MHz) δ (ppm): 3,53 (K, 3H, J=1.2 Hz), 3,79 (s, 3H), 6,33 (s, 1H), 6,6-6,7 (m, 2H), 6,7-6,8 (m, 1H), 7,00 (d, 1H, J=6,1 Hz), 7,2-7,3 (m, 1H), 7,88 (d, 1H, J=8.6 Hz)

The second method is:

A solution of 4.17 g of 5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene in 10 ml of acetic acid is added dropwise during 20 minutes to a mixture of 4.5 g of iron powder, 10 ml acetic acid and 1 ml of water. After the addition the mixture is stirred for 2 hours, filtered through celite and diluted with ethyl acetate. The resulting solution was washed with water 2 times, the organic layer was washed with saturated aqueous sodium bicarbonate and saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel with getting to 3.67 g of 5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,52 (K, 3H, J=1.0 Hz), 3,76 (s, 3H), 4,0-4,2 (W, 2N), of 6.31 (s, 1H), 6,5-6,7 (m, 4H), 6.73 x (d, 1H, J=7,0 Hz), 7,1-7,3 (m, 1H)

The third way:

To a mixture of 213 mg of 5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl] aniline, 93 mg of copper bromide (I) and 1 ml of acetonitrile added 57 mg of tert-butylnitrite dropwise over 1 hour at 0°C. the Mixture is stirred for 30 minutes, then allowed to warm to room temperature and ne is amerivault for 10 hours. The reaction mixture was poured into 2% hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 75 mg of 5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifter-methyl)-1,2,3,6-tetrahydropyrimidin-1-yl]bromine benzol.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,52 (K, 3H, J=1.2 Hz), of 3.77 (s, 3H), of 6.31 (s, 1H), 6,5-6,6 (m, 1H), 6,59 (s, 1H), and 6.6 and 6.7 (m, 1H), 6,86 (d, 1H, J=6,7 Hz), 7,22 (DD, 1H, J=9,0 Hz, 8.7 Hz), 7,54 (d, 1H, J=8,8 Hz)

The fourth way:

A mixture of 75 mg of 5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-bromine benzol, 27 mg of copper cyanide and 0.5 ml of N-methyl-2-pyrrolidone was stirred at 170-180°C for 2 hours. The reaction mixture is cooled to room temperature, add water to the mixture and extracted with ethyl acetate. The organic layer is dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 57 mg of 5-fluoro-2-(3-methoxyphenoxy)-4-[L-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]qi-azobenzol.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,52 (K, 3H, J=1.0 Hz), 3,79 (s, 3H), of 6.31 (s, 1H), of 6.31 (s, 1H), to 6.67 (s, 1H), and 6.6 and 6.7 (m, 1H), 6,7-6,8 (m, 1H), at 6.84 (d, 1H, J=5.8 Hz), 7,29 (DD, 1H, J=9/1, 8.6 Hz), 7,53 (d, 1H, J=8,4 Hz)

The fifth is the procedure;

To a solution of 57 mg of 5-fluoro-2-(3-methoxyphenoxy)-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]cyanobenzoyl in 0.6 ml of chloroform is added dropwise 48 ál tribromide boron at 0°C. After the addition the temperature of the reaction mixture was raised to room temperature and stirred for 1 hour. The mixture is cooled to 0°and to it was added 1 ml of methanol. The solvent is removed under reduced pressure, the residue diluted with ethyl acetate and then add saturated aqueous sodium bicarbonate solution to pH 4. The resulting solution was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel to obtain 36 mg of 3-{2-cyano-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,52 (K, 3H, J=1.0 Hz), 6,32 (s, 1H), 6,3-6,5 (W, 1H), 6,5-6,6 (m, 1H), 6,6-6,7 (m, 2H), 6.87 in (d, 1H, J=5.8 Hz), 7,21 (DD, 1H, J=8,3 Hz, 8.1 Hz), 7,51 (d, 2H, J=8,4 Hz)

Example 10 to obtain intermediate products: Obtain 5-fluoro-2-{2-(methoxycarbonyl)methoxyphenoxy}-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl] aniline

To a solution of 19 g of iron powder, 60 ml of acetic acid and 6 ml of water is added dropwise under ice cooling a solution of 19,12 g 5-fluoro-2-{2-(m is oxycarbonyl)methoxyphenoxy}-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene [Join 4-19 of the present invention] in 60 ml of acetic acid. After the addition the temperature of the reaction mixture was raised to room temperature and the mixture is stirred for 4 hours. The reaction mixture is filtered with sellita and diluted with ethyl acetate. Dilute the filtrate is washed with water, saturated aqueous sodium bicarbonate and saturated saline, dried over anhydrous magnesium sulfate and concentrated. The residue is subjected to column chromatography on silica gel with getting 15,16 g 5-fluoro-2-{2-(methoxycarbonyl)-methoxyphenoxy}-4-[3-Methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline.

1H-NMR (CDCl3, 250 MHz) δ (ppm): 3,51 (K, 3H, J=0.9 Hz), 3,76 (s, 3H), 4,2-4,4 (W, 2H), 4,69 (s, 2H), 6,29 (s, 1H), 6,6-6,7 (m, 2H), 6,9-7,1 (m, 4H)

Example 11 to obtain intermediate products: Obtain methyl-[2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenyl)-phenoxy]acetate [Intermediate compound A9-22]

The first method is:

4-chloro-2-fluoro-5-(2-hydroxyphenoxy)aniline [Intermediate compound A3-4] is obtained from N-[4-chloro-2-fluoro-5-(2-hydroxyphenoxy)phenyl]ndimethylacetamide (obtained in the third process Example 6 to obtain the intermediate compounds) in accordance with the sixth method of Example 5 to obtain the intermediate compounds.

1H-NMR (CDCl3, 300 MHz) δ (ppm): 3,76 (CL, 2H), 5,78 (SHS, 1H), 6,41 (d, 1H, J=8,3 Hz), 6,7-6,9 (m, 2H), between 7.0 and 7.1 (m, 2H), to 7.09 (d, 1H, J=10,2 Hz)

The second method is:

In a mixture of 4-chloro-2-fluoro-5(2-hydroxyphenoxy)aniline [Intermediate compounds A3-4], methylcarbamate and tetrahydrofuran is added dropwise N,N-dimethylaniline and the mixture is stirred at room temperature. To the reaction solution add dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated to obtain 2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenyl)phenol [Intermediate compound A9-4]

The third way:

2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenyl)phenol [Intermediate compound A9-4] dissolved in N,N-dimethylformamide, then add the potassium carbonate and the mixture is stirred for 1 hour at room temperature. Then add bromoacetate at room temperature. The mixture was stirred at 60°C for 2 hours, poured into water, extracted with ethyl acetate and the organic layer washed with diluted hydrochloric acid and water, dried over magnesium sulfate and concentrated to obtain methyl-[2-(2-chloro-4-fluoro-5-methoxycarbonylaminophenyl)phenoxy]acetate [Intermediate compound A9-22].

Hereinafter cited as examples of some compounds of the present invention. Specific compounds are described by the compounds described in tables 1-5. The compounds of this invention are not limited to those listed as the reamers connections.

All compounds listed in the tables below can be obtained by methods disclosed and illustrated in the examples above.

The compound of the formula [I-1] (numbers of compounds described in table 1)

Table 1

Connection # X3X4And
1-1NNOCH(CH3)CO2CH3
1-2NNOCH(CH3)CO3CH2CH3
1-3NNOCH(CH3)CO2CH2CH2CH3
1-4NNOCH(CH3)CO2CH2CH2CH2CH3
1-5NNOCH(CH3)CO2CH(CH3)2
1-6NNOCH(CH3)CO2C(CH3)3
1-7NNOCH(CH3)CO2CH2CH2F
1-8NNOCH(CH3)CO2CH2CH2Cl
1-9NNOCH(CH3)CO2CH2CCl3
1-10NNOCH(CH3)CO2CH2CH=CH2
1-11NNOCH2CO2CH3
1-12NNOCH2CO2CH2CH3
1-13NNOCH2CO2CH2CH2CH3

Connection # X3X4And
1-14NNOCH2CO2CH2CH2CH2CH3
1-15NNOCH2CO2CH(CH3)2
1-16NNOCH2CO2C(CH3)3
1-17NNOCH2CO2CH2CH2F
1-18NNOCH2CO2CH2CH2Cl
1-19NNOCH2CO2CH2 CCl3
1-20NNOCH2CO2CH2CH=CH2
1-21NNSCH(CH3)CO2CH3
1-22NNSCH(CH3)CO2CH2CH3
1-23NNSCH(CH3)CO2CH2CH2CH2CH3
1-24NNSCH(CH3)CO2CH2CH2CH3
1-25NNSCH(CH3)CO2CH(CH3)2
1-26NNSCH(CH3)CO2C(CH3)3
1-27NNSCH(CH3)CO2CH2CH2F
1-28NNSCH(CH3)CO2CH2CH2Cl
1-29NNSCH(CH3)CO2CH2CCl3
1-30NNSCH(CH3)CO2CH2CH=CH2
1-31NNSCH2CO2SN 3
1-32NNSCH2CO2CH2CH3
1-33NNSCH2CO2CH2CH2CH3
1-34NNSCH2CO2CH2CH2CH2CH3
1-35NNSCH2CO2CH(CH3)2
1-36NNSCH2CO2C(CH3)3
1-37NNSCH2CO2CH2CH2F
1-38NNSCH2CO2CH2CH2Cl

Connection # X3X4And
1-39NNSCH2CO2CH2CCl3
1-40NNSCH2CO2CH3CH=CH2
1-413-CH3NOCH(CH3)CO2CH3
1-423-CH3N1-433-CH3NOCH(CH3)CO2CH2CH2CH3
1-443-CH3NOCH(CH3)CO2CH2CH2CH2CH3
1-453-CH3NOCH(CH3)CO2CH(CH3)2
1-463-CH3NOch(CH3)CO2C(CH3)3
1-473-CH3NOch(CH3)CO2CH2CH2F
1-483-CH3NOch(CH3)CO2CH2CH2Cl
1-493-CH3NOch(CH3)CO2CH2CCl3
1-503-CH3NOch(CH3)CO2CH2CH=CH2

Connection # X3X4And
1-513-CH3NOch2CO2CH3
1-52 3-CH3NOch2CO2CH2CH3
1-533-CH3NOch2CO2CH2CH2CH3
1-543-CH3NOch2CO2CH2CH2CH2CH3
1-553-CH3NOch2CO2CH(CH3)2
1-563-CH3NOch2CO2C(CH3)3
1-573-CH3NOch2CO2CH2CH2F
1-583-CH3NOch2CO2CH2CH2Cl
1-593-CH3NOch2CO2CH2CCl3
1-603-CH3NOch2CO2CH2CH=CH2
1-613-CH3NOch(CH3)CO2CH2CH2CH2CH3
1-622-CH3NOch(CH3)CO2CH3
1-632-CH3NOch(CH3)CO2CH2CH3
1-642-CH3NOch(CH3)CO2CH2CH2CH3
1-652-CH3NOch(CH3)CO2CH(CH3)2
1-662-CH3NOch(CH3)CO2C(CH3)3
1-672-CH3NOch(CH3)CO2CH2CH2F
1-682-CH3NOch(CH3)CO2CH2CH2Cl
1-692-CH3NOch(CH3)CO2CH2CCl3
1-702-CH3NOch(CH3)CO2CH2CH=CH2
1-712-CH3NOch2CO2CH2CH2CH2CH3
1-722-CH3NOch2CO2CH3
1-732-CH3NOch2CO CH2CH3
1-742-CH3NOch2CO2CH2CH2CH3
1-752-CH3NOch2CO2CH(CH3)2

3-och3
Connection # X3X4And
1-762-CH3NOch2CO2C(CH3)3
1-772-CH3NOch2CO2CH2CH2F
1-782-CH3NOch2CO2CH2CH2Cl
1-792-CH3NOch2CO2CH2CCl3
1-802-CH3NOch2CO2CH2CH=CH2
1-813-och3NOch(CH3)CO2CH3
1-823-och3NOch(CH3)CO2CH2CH3
1-833-och3N Och(CH3)CO2CH2CH2CH3
1-843-och3NOch(CH3)CO2CH2CH2CH2CH3
1-853-och3NOch(CH3)CO2CH(CH3)2
1-863-och3NOch(CH3)CO2C(CH3)3
1-873-och3NOch(CH3)CO2CH2CH2F
1-883-och3NOch(CH3)CO2CH2CH2Cl
1-893-och3NOch(CH3)CO2CH2CCl3
1-903-och3NOch(CH3)CO2CH2CH=CH2
1-913-och3NOch2CO2CH3
1-923-och3NOch2CO2CH2CH3
1-933-och3NOch2CO2CH2CH2CH3
1-94NOch2CO2CH2CH2CH2CH3
1-953-och3NOch2CO2CH(CH3)2
1-963-och3NOch2CO2C(CH3)3
1-973-och3NOch2CO2CH2CH2F
1-983-och3NOch2CO2CH2CH2Cl
1-993-och3NOch2CO2CH2CCl3
1-1003-och3NOch2CO2CH2CH=CH2

Connection # X3X4And
1-1012-och3NOch(CH3)CO2CH3
1-1022-och3NOch(CH3)CO2CH2CH3
1-1032-och3NOch(CH3)CO2CH2With the 2CH3
1-1042-och3NOch(CH3)CO2CH2CH2CH3CH3
1-1052-och3NOch(CH3)CO2CH(CH3)2
1-1062-och3NOch(CH3)CO2C(CH3)3
1-1072-och3NOch(CH3)CO2CH2CH2F
1-1082-och3NOch(CH3)CO2CH2CH2Cl
1-1092-och3NOch(CH3)CO2CH2CCl3
1-1102-och3NOch(CH3)CO2CH2CH=CH2
1-1112-och3NOch2CO2CH3
1-1122-och3NOch2CO2CH2CH3
1-1132-och3NOch2CO2CH2CH2CH3
1-1142-och3 NOch2CO2CH2CH2CH2CH3
1-1152-och3NOch2CO2CH(CH3)2
1-1162-och3NOch2CO2C(CH3)3
1-1172-och3NOch2CO2CH2CH2F
1-1182-och3NOch2CO2CH2CH2Cl
1-1192-och3NOch2CO2CH2CCl3
1-1202-och3NOch2CO2CH2CH=CH2
1-1213-ClNOch(CH3)CO2CH3
1-1223-ClNOch(CH3)CO2CH2CH3
1-1233-ClNOch(CH3)CO2CH2CH2CH3
1-1243-ClNOch(CH3)CO2CH2CH2CH2CH3
1-1253-Cl NOch(CH3)CO2CH(CH3)2

Connection # X3X4And
1-1263-ClNOch(CH3)CO2C(CH3)C
1-1273-ClNOch(CH3)CO2CH2CH2F
1-1283-ClNOch(CH3)CO2CH2CH2Cl
1-1293-ClNOch(CH3)CO2CH2CCl3
1-1303-ClNOch(CH3)CO2CH2CH=CH2
1-1313-ClNOch2CO2CH3
1-1323-ClNOch2CO2CH2CH3
1-1333-ClNOch2CO2CH2CH2CH3
1-1343-ClNOch2CO2CH2CH2CH2CH3
1-1353-ClNOch2CO2The n(CH 3)2
1-1363-ClNOch2CO2C(CH3)3
1-1373-ClNOch2CO2CH2CH2F
1-1383-ClNOch2CO2CH2CH2Cl
1-1393-ClNOch2CO2CH2CCl3
1-1403-ClNOch2CO2CH2CH=CH2
1-1412-ClNOch(CH3)CO2CH3
1-1422-ClNOch(CH3)CO2CH2CH3
1-1432-ClNOch(CH3)CO2CH2CH2CH3
1-1442-ClNOch(CH3)CO2CH2CH2CH2CH3
1-1452-ClNOch(CH3)CO2CH(CH3)2
1-1462-ClNOch(CH3)CO2C(CH3)3
1-1472-Cl Och(CH3)CO2CH2CH2F
1-1482-ClNOch(CH3)CO2CH2CH2Cl
1-1492-ClNOch(CH3)CO2CH2CCl3
1-1502-ClNOch(CH3)CO2CH2CH=CH2

Connection # X3X4And
1-1512-ClNOch2CO2CH3
1-1522-ClNOch2CO2CH2CH3
1-1532-ClNOch2CO2CH2CH3CH3
1-1542-ClNOch2CO3CH2CH2CH2CH3
1-1552-ClNOch2CO2CH(CH3)2
1-1562-ClNOch2CO2C(CH3)2
1-1572-ClNOch2CO2SN 2CH2F
1-1582-ClNOch2CO2CH2CH2Cl
1-1592-ClNOch2CO2CH2CCl3
1-1602-ClNOch2CO2CH2CH=CH2
1-161NNNHCH(CH3)CO2CH3
1-162NNNHCH(CH3)CO2CH2CH3
1-163NNNHCH(CH3)CO2CH2CH2CH3
1-164NNNHCH(CH3)CO2CH2CH2CH2CH3
1-165NNNHCH(CH3)CO2CH(CH3)2
1-166NNNHCH(CH3)CO2C(CH3)3
1-167NNNHCH(CH3)CO2CH2CH2F
1-168NNNHCH(CH3)CO2CH2CH2Cl
1-169NNHCH(CH 3)CO2CH2CCl3
1-170NNNHCH(CH3)CO2CH2CH=CH2
1-171NNNHCH2CO2CH3
1-172NNNHCH2CO2CH2CH3
1-173NNNHCH2CO2CH2CH2CH3
1-174NNNHCH2CO2CH2CH2CH2CH3
1-175NNNHCH2CO2CH(CH3)2

Connection # X3X4And
1-176NNNHCH2CO2C(CH3)3
1-177NNNHCH2CO2CH2CH2F
1-178NNNHCH2CO2CH2CH2Cl
1-179NNNHCH2CO2CH2CCl3
1-180N/td> NNHCH2CO2CH2CH=CH2
1-181NNN(CH3)CH(CH3)CO2CH3
1-182NNN(CH3)CH(CH3)CO2CH2CH3
1-183NNN(CH3)CH2CO2CH3
1-184NNN(CH3)CH2CO2CH2CH3
1-185NNN(CH3)CH2CO2CH2CH2CH2
1-186NNOch(CH3)CO2CH2CH2CH=CH2
1-187NNOch(CH3)CO2CH2CH(CH3)2
1-188NNOch(CH3)CO2CH(CH3)CH2CH3
1-189NNOch(CH3)CO3CH2CH2CH2CH2CH3
1-190NNOch(CH3)CO2CH2CH2CH(CH3)2
1-191NNOch(CH3)CO2CH2CH(CH3)CH2CH3
1-192NNOch(CH3)CO2CH(CH3)CH2CH2CH3
1-193NNOCH(CH3)CO2C(CH3)2CH2CH3
1-194NNOch(CH3)CO2CH(CH3)CH(CH3)2
1-195NNOch(CH3)CO2CH2C(CH3)3
1-196NNOch(CH3)CO2CH2C=CH
1-197NNOCH(CH3)CO2CH2CH2CH=CH2
1-198NNOch2CO2CH2CH(CH3)2
1-199NNOch2CO2CH(CH3)CH2CH3
1-200NNOch2CO2CH2CH2CH2CH2CH3
1-201NNOch2With the 2CH2With≡SN

The compound of the formula [I-2] (number of compounds described in table 2.

Table 2

Connection # X3X4And
2-1NNOch(CH3)CO2CH3
2-2NNOch(CH3)CO2CH2CH3
2-3NNOch(CH3)CO3CH2CH2CH3
2-4NNOch(CH3)CO2CH2CH2CH2CH3
2-5NNOch(CH3)CO2CH(CH3)2
2-6NNOch(CH3)CO2C(CH3)3
2-7NNOch(CH3)CO2CH2CH2F
2-8NNOch(CH3)CO2CH2CH2Cl
2-9NNOch(CH3)CO2CH 2CCl3
2-10NNOch(CH3)CO2CH2CH=CH2
2-11NNOch2CO2CH3
2-12NNOch2CO2CH2CH3
2-13NNOch2CO2CH2CH2CH3

Connection # X3X4And
2-14NNOch2CO2CH2CH2CH2CH3
2-15NNOch2CO2CH(CH3)2
2-16NNOch2CO2C(CH3)3
2-17NNOch2CO2CH2CH2F
2-18NNOch2CO2CH2CH2Cl
2-19NNOch2CO2CH2CCl3
2-20N NOch2CO2CH2CH=CH2
2-21NNSCH(CH3)CO2CH3
2-22NNSCH(CH3)CO2CH2CH3
2-23NNSCH(CH3)CO2CH2CH2CH2CH3
2-24NNSCH(CH3)CO2CH2CH2CH3
2-25NNSCH(CH3)CO2CH(CH3)2

Connection # X3X4And
2-26NNSCH(CH3)CO2C(CH3)3
2-27NNSCH(CH3)CO2CH2CH2F
2-28NNSCH(CH3)CO2CH2CH2Cl
2-29NNSCH(CH3)CO2CH2CCl3
2-30NNSCH(CH3)CO2CH2SN=With the 2
2-31NNSCH2CO2CH3
2-32NNSCH2CO2CH2CH3
2-33NNSCH2CO2CH2CH2CH3
2-34NNSCH2CO2CH2CH2CH2CH3
2-35NNSCH2CO2CH(CH3)2
2-36NNSCH2CO2C(CH3)3
2-37NNSCH2CO2CH2CH2F
2-38NNSCH2CO2CH2CH2Cl
2-39NNSCH2CO2CH2CCl3
2-40NNSCH2CO2CH2CH=CH2
2-414-CH3NOch(CH3)CO2CH3
2-424-CH3NOch(CH3)CO2CH2The h 3
2-434-CH3NOch(CH3)CO2CH2CH2CH3
2-444-CH3NOch(CH3)CO2CH2CH2CH2CH3
2-454-CH3NOch(CH3)CO2CH(CH3)2
2-464-CH3NOch(CH3)CO2C(CH3)3
2-474-CH3NOch(CH3)CO2CH2CH2F
2-484-CH3NOch(CH3)CO2CH2CH2Cl
2-494-CH3NOch(CH3)CO2CH2CCl3
2-504-CH3NOch(CH3)CO2CH2CH=CH2

Connection # X3X4And
2-514-CH3NOch2CO2CH3
2-524-CH3 NOch2CO2CH2CH3
2-534-CH3NOch2CO2CH2CH2CH3
2-544-CH3NOch2CO2CH2CH2CH2CH3
2-554-CH3NOch2CO2CH(CH3)2
2-564-CH3NOch2CO2C(CH3)3
2-574-CH3NOch2CO2CH2CH2F
2-584-CH3NOch2CO2CH2CH2Cl
2-594-CH3NOch2CO2CH2CCl3
2-604-CH3NOch2CO2CH2CH=CH2
2-612-CH3NOch(CH3)CO2CH2CH2CH2CH3
2-622-CH3NOch(CH3)CO2CH3
2-63 2-CH3NOch(CH3)CO2CH2CH3
2-642-CH3NOch(CH3)CO2CH2CH2CH3
2-652-CH3NOch(CH3)CO2CH(CH3)2
2-662-CH3NOch(CH3)CO2C(CH3)3
2-672-CH3NOch(CH3)CO2CH2CH2F
2-682-CH3NOch(CH3)CO2CH2CH2Cl
2-692-CH3NOch(CH3)CO2CH2CCl3
2-702-CH3NOch(CH3)CO2CH2CH=CH2
2-712-CH3NOch2CO2CH2CH2CH2CH3
2-722-CH3NOch2CO2CH3
2-732-CH3NOch2CO2CH2CH3
2-742-CH3NOch2CO2CH2CH2CH3
2-752-CH3NOch2CO2CH(CH3)2

Connection # X3X4And
2-762-CH3NOch2CO2C(CH3)3
2-772-CH3NOch2CO2CH2CH2F
2-782-CH3NOch2CO2CH2CH2Cl
2-792-CH3NOch2CO2CH2CCl3
2-802-CH3NOch2CO2CH2CH=CH2
2-814-och3NOch(CH3)CO2CH3
2-824-och3NOch(CH3)CO2CH2CH3
2-834-och3NOch(CH3)CO2sub> 2CH2CH3
2-844-och3NOch(CH3)CO2CH2CH2CH2CH3
2-854-och3NOch(CH3)CO2CH(CH3)2
2-864-och3NOch(CH3)CO2C(CH3)3
2-874-och3NOch(CH3)CO2CH3CH2F
2-884-och3NOch(CH3)CO2CH2CH2Cl
2-894-och3NOch(CH3)CO2CH2CCl3
2-904-och3NOch(CH3)CO2CH2CH=CH2
2-914-och3NOch2CO2CH3
2-924-och3NOch2CO2CH2CH3
2-934-och3NOch2CO2CH2CH2CH3
2-944-och3 NOch2CO2CH2CH2CH2CH3
2-954-och3NOch2CO2CH(CH3)2
2-964-och3NOch2CO2C(CH3)3
2-974-och3NOch2CO2CH2CH2F
2-984-och3NOch2CO2CH2CH2Cl
2-994-och3NOch2CO2CH2CCl3
2-1004-och3NOch2CO2CH2CH=CH2

2-104
Connection # X3X4And
2-1012-och3NOch(CH3)CO2CH3
2-1022-och3NOCH(CH3)CO2CH2CH3
2-1032-och3NOCH(CH3)CO2CH2CH2CH3
2-och3NOCH(CH3)CO2CH2CH2CH2CH3
2-1052-och3NOCH(CH3)CO2CH(CH3)2
2-1062-och3NOch(CH3)CO2C(CH3)3
2-1072-och3NOCH(CH3)CO2CH2CH2F
2-1082-och3NOch(CH3)CO2CH2CH2Cl
2-1092-och3NOCH(CH3)CO2CH2CCl3
2-1102-och3NOCH(CH3)CO2CH2CH=CH2
2-1112-och3NOch2CO2CH3
2-1122-och3NOch2CO2CH2CH3
2-1132-och3NOch2CO2CH2CH2CH3
2-1142-och3NOch2CO2With the 2CH2CH2CH3
2-1152-och3NOch2CO2CH(CH3)2
2-1162-och3NOch2CO2C(CH3)3
2-1172-och3NOch2CO2CH2CH2F
2-1182-och3NOch2CO2CH2CH2Cl
2-1192-och3NOch2CO2CH2CCl3
2-1202-och3NOch2CO2CH2CH=CH2
2-1214-ClNOCH(CH3)CO2CH3
2-1224-ClNOCH(CH3)CO2CH2CH3
2-1234-ClNOCH(CH3)CO2CH2CH2CH3
2-1244-ClNOCH(CH3)CO2CH2CH2CH2CH3
2-1254-ClNOCH(CH3)CO2SN(the N 3)2

Connection # X3X4And
2-1264-ClNOch(CH3)CO2C(CH3)3
2-1274-ClNOch(CH3)CO2CH2CH2F
2-1284-ClNOch(CH3)CO2CH2CH2Cl
2-1294-ClNOch(CH3)CO2CH2CCl3
2-1304-ClNOch(CH3)CO2CH2CH=CH2
2-1314-ClNOch2CO2CH3
2-1324-ClNOch2CO2CH2CH3
2-1334-ClNOch2CO2CH2CH2CH3
2-1344-ClNOch2CO2CH2CH2CH2CH3
2-1354-ClNOch3CO2CH(CH3)2
2-36 4-ClNOch2CO2C(CH3)3
2-1374-ClNOch2CO2CH2CH2F
2-1384-ClNOch2CO2CH2CH2Cl
2-1394-ClNOch2CO2CH2CCl3
2-1404-ClNOch2CO2CH2CH=CH2
2-1412-ClNOch(CH3)CO2CH3
2-1422-ClNOch(CH3)CO2CH2CH3
2-1432-ClNOch(CH3)CO2CH2CH2CH3
2-1442-ClNOch(CH3)CO2CH2CH2CH2CH3
2-1452-ClNOch(CH3)CO2CH(CH3)2
2-1462-ClNOch(CH3)CO2C(CH3)3
2-1472-ClNOch(CH3)CO2 CH2CH2F
2-1482-ClNOch(CH3)CO2CH2CH2Cl
2-1492-ClNOch(CH3)CO2CH2CCl3
2-1502-ClNOch(CH3)CO2CH2CH=CH2

Connection # X3X4And
2-1512-ClNOch2CO2CH3
2-1522-ClNOch2CO2CH2CH3
2-1532-ClNOch2CO2CH2CH2CH3
2-1542-ClNOch2CO2CH2CH2CH2CH3
2-1552-ClNOch2CO2CH(CH3)2
2-1562-ClNOch2CO2C(CH3)3
2-1572-ClNOch2CO2CH2CH2F
2-ClNOch2CO2CH2CH2Cl
2-1592-ClNOch2CO2CH2CCl3
2-1602-ClNOch2CO2CH2CH=CH2
2-161NNNHCH(CH3)CO2CH3
2-162NNNHCH(CH3)CO2CH2CH3
2-163NNNHCH(CH3)CO2CH2CH2CH3
2-164NNNHCH(CH3)CO2CH2CH2CH2CH3
2-165NNNHCH(CH3)CO2CH(CH3)2
2-166NNNHCH(CH3)CO2C(CH3)3
2-167NNNHCH(CH3)CO2CH2CH2F
2-168NNNHCH(CH3)CO2CH2CH2Cl
2-169NNNHCH(CH3)CO2CH2CCl3
2-170NNNHCH(CH3)CO2CH2CH=CH2
2-171NNNHCH2CO2CH3
2-172NNNHCH2CO2CH2CH3
2-173NNNHCH2CO2CH2CH2CH3
2-174NNNHCH2CO2CH2CH2CH2CH3
2-175NNNHCH2CO2CH(CH3)2

Connection # X3X4And
2-176NNNHCH2CO2C(CH3)3
2-177NNNHCH2CO2CH2CH2F
2-178NNNHCH2CO2CH2CH2Cl
2-179NNNHCH2CO2CH2CCl3
2-180NNNHCHsub> 2CO2CH2CH=CH2
2-181NNN(CH3)CH(CH3)CO2CH3
2-182NNN(CH3)CH(CH3)CO2CH2CH3
2-183NNN(CH3)CH2CO2CH3
2-184NNN(CH3)CH2CO2CH2CH3
2-185NNN(CH3)CH2CO2CH2CH2CH3
2-186NNOch(CH3)CO2CH2CH2CH=CH2
2-187NNOch(CH3)CO2CH2CH(CH3)2
2-188NNOch(CH3)CO2CH(CH3)CH2CH3
2-189NNOch(CH3)CO2CH2CH2CH2CH2CH3
2-190NNOch(CH3)CO2CH2CH2CH(CH3)2
2-191N NOch(CH3)CO2CH2CH(CH3)CH2CH3
2-192NNOch(CH3)CO2CH(CH3)CH2CH2CH3
2-193NNOch(CH3)CO2C(CH3)2CH2CH3
2-194NNOch(CH3)CO2CH(CH3)CH(CH3)2
2-195NNOch(CH3)CO2CH2C(CH3)3
2-196NNOch(CH3)CO2CH2With≡SN
2-197NNOch(CH3)CO2CH2CH2CH=CH2
2-198NNOch2CO2CH2CH(CH3)2
2-199NNOch2CO2CH(CH3)CH2CH3
2-200NNOch2CO2CH2CH2CH2CH2CH3
2-201NNOch2CO2CH2With≡is N

The compound of the formula [I-3] (number of compounds described in table 3

3-10
Table 3

Connection # X3X4And
3-1NNOch(CH3)CO2CH3
3-2NNOch(CH3)CO2CH2CH3
3-3NNOch(CH3)CO2CH2CH2CH3
3-4NNOch(CH3)CO2CH2CH2CH2CH3
3-5NNOch(CH3)CO2CH(CH3)2
3-6NNOch(CH3)CO2C(CH3)3
3-7NNOch(CH3)CO2CH2CH2F
3-8NNOch(CH3)CO2CH2CH2Cl
3-9NNOch(CH3)CO2CH2CCl3
NNOch(CH3)CO2CH2CH=CH2
3-11NNOch2CO2CH3
3-12NNOch2CO2CH2CH3
3-13NNOch2CO2CH2CH2CH3
3-14NNOch2CO2CH2CH2CH2CH3
3-15NNOch2CO2CH(CH3)2
3-16NNOch2CO2C(CH3)3
3-17NNOch2CO2CH2CH2F
3-18NNOch2CO2CH2CH2Cl
3-19NNOch2CO2CH2CCl3
3-20NNOch2CO2CH2CH=CH2
3-21NNSCH(CH3)CO2CH3
3-22NNSCH(CH3)CO2CH2CH3
3-23NNSCH(CH3)CO2CH2CH2CH2CH3
3-24NNSCH(CH3)CO2CH2CH2CH3
3-25NNSCH(CH3)CO2CH(CH3)2

Connection # X3X4And
3-26NNSCH(CH3)CO2C(CH3)3
3-27NNSCH(CH3)CO2CH2CH2F
3-28NNSH(CH3)CO2CH2CH2Cl
3-29NNSCH(CH3)CO2CH2CCl3
3-30NNSCH(CH3)CO2CH2CH=CH2
3-31NNSCH2CO2CH3
3-32NNSCH2 CO2CH2CH3
3-33NNSCH2CO2CH2CH2CH3
3-34NNSCH2CO2CH2CH2CH2CH3
3-35NNSCH2CO2CH(CH3)2
3-36NNSCH2CO2C(CH3)3
3-37NNSCH2CO2CH2CH2F
3-38NNSCH2CO2CH2CH2Cl
3-39NNSCH2CO2CH2CCl3
3-40NNSCH2CO2CH2CH=CH2
3-413-CH3NOch(CH3)CO2CH3
3-423-CH3NOch(CH3)CO2CH2CH3
3-433-CH3NOch(CH3)CO2CH2CH2CH3
3-44SN 3NOch(CH3)CO2CH2CH2CH2CH3
3-453-CH3NOch(CH3)CO2CH(CH3)2
3-463-CH3NOch(CH3)CO2C(CH3)3
3-473-CH3NOch(CH3)CO2CH2CH2F
3-483-CH3NOch(CH3)CO2CH2CH2Cl
3-493-CH3NOch(CH3)CO2CH2CCl3
3-503-CH3NOch(CH3)CO2CH2CH=CH2

Connection # X3X4And
3-513-CH3NOch2CO2CH3
3-523-CH3NOch2CO2CH2CH3
3-533-CH3NOch2CO2CH2CH2 CH3
3-543-CH3NOch2CO2CH2CH2CH2CH3
3-553-CH3NOch2CO2CH(CH3)2
3-563-CH3NOch2CO2C(CH3)3
3-573-CH3NOch2CO2CH2CH2F
358 for3-CH3NOch2CO2CH2CH2Cl
3-593-CH3NOch2CO2CH2Cl3
3-603-CH3NOch2CO2CH2CH=CH2
3-614-CH3NOch(CH3)CO2CH2CH2CH2CH3
3-624-CH3NOch(CH3)CO2CH3
3-634-CH3NOch(CH3)CO2CH2CH3
3-644-CH3NCore(With the 3)CO2CH2CH2CH3
3-654-CH3NOch(CH3)CO2CH(CH3)2
3-664-CH3NOch(CH3)CO2C(CH3)3
3-674-CH3NOch(CH3)CO2CH2CH2F
3-684-CH3NOch(CH3)CO2CH2CH2Cl
3-694-CH3NOch(CH3)CO2CH2CCl3
3-704-CH3NOch(CH3)CO2CH2CH=CH2
3-714-CH3NOch2CO2CH2CH2CH2CH3
3-724-CH3NOch2CO2CH3
3-734-CH3NOch2CO2CH2CH3
3-744-CH3NOch2CO2CH2CH2CH3
3-754-CH3 NOch2CO2CH(CH3)2

Connection # X3X4And
3-764-CH3NOch2CO2C(CH3)3
3-774-CH3NOch2CO2CH2CH2F
3-784-CH3NOch2CO2CH2CH2Cl
3-794-CH3NOch2CO2CH2CCl3
3-804-CH3NOch2CO2CH2CH=CH2
3-813-och3NOch(CH3)CO2CH3
3-823-och3NOch(CH3)CO2CH2CH3
3-833-och3NOCH(CH3)CO2CH2CH2CH3
3-843-och3NOch(CH3)CO2CH2CH2CH2CH3
3-853-och3NOch(CH3)CO2CH(CH3)2
3-863-och3NOch(CH3)CO2C(CH3)3
3-873-och3NOch(CH3)CO2CH2CH2F
3-883-och3NOch(CH3)CO2CH2CH2Cl
3-893-och3NOch(CH3)CO2CH2CCl3
3-903-och3NOch(CH3)CO2CH2CH=CH2
3-913-och3NOch2CO2CH3
3-923-och3NOch2CO2CH2CH3
3-933-och3NOch2CO2CH2CH3CH3
3-943-och3NOch2CO2CH2CH2CH2CH3
3-953-och3NOch2 CO2CH(CH3)2
3-963-och3NOch2CO2C(CH3)3
3-973-och3NOch2CO2CH2CH2F
3-983-och3NOch2CO2CH2CH2Cl
3-993-och3NOch2CO2CH2CCl3
3-1003-och3NOch2CO2CH2CH=CH2

Connection # X3X4And
3-1014-och3NOch(CH3)CO2CH3
3-1024-och3NOch(CH3)CO2CH2CH3
3-1034-och3NOch(CH3)CO2CH2CH2CH3
3-1044-och3NOch(CH3)CO2CH2CH2CH2CH3
3-105 4-och3NOch(CH3)CO2CH(CH3)2
3-1064-och3NOch(CH3)CO2C(CH3)3
3-1074-och3NOch(CH3)CO2CH2CH2F
3-1084-och3NOch(CH3)CO2CH2CH2Cl
3-1094-och3NOch(CH3)CO2CH2CCl3
3-1104-och3NOch(CH3)CO2CH2CH=CH2
3-1114-och3NOch2CO2CH3
3-1124-och3NOch2CO2CH2CH3
3-1134-och3NOch2CO2CH2CH2CH3
3-1144-och3NOch2CO2CH2CH2CH2CH3
3 through 1154-och3NOch2CO2CH(CH3) 2
3-1164-och3NOch2CO2C(CH3)3
3-1174-och3NOch2CO2CH2CH2F
3-1184-och3NOch2CO2CH2CH2Cl
3-1194-och3NOch2CO2CH2CCl3
3-1204-och3NOch2CO2CH2CH=CH2
3-1213-ClNOch(CH3)CO2CH3
3-1223-ClNOch(CH3)CO2CH2CH3
3-1233-ClNOch(CH3)CO2CH2CH2CH3
3-1243-ClNOch(CH3)CO2CH2CH2CH2CH3
3-1253-ClNOch(CH3)CO2CH(CH3)2

Connection # X3X And
3-1263-ClNOch(CH3)CO2C(CH3)3
3-1273-ClNOch(CH3)CO2CH2CH2F
3-1283-ClNOch(CH3)CO2CH2CH3Cl
3-1293-ClNOch(CH3)CO2CH2CCl3
3-1303-ClNOch(CH3)CO2CH2CH=CH2
3-1313-ClNOch2CO2CH3
3-1323-ClNOch2CO2CH2CH3
3-1333-ClNOch2CO2CH2CH2CH3
3-1343-ClNOch2CO2CH2CH2CH2CH3
3-1353-ClNOch2CO2CH(CH3)2
3-1363-ClNOch2CO2C(CH3)3
3-1373-ClN Och2CO2CH2CH2F
3-1383-ClNOch2CO2CH2CH2Cl
3-1393-ClNOch2CO2CH2CCl3
3-1403-ClNOch2CO2CH2CH=CH2
3-1414-ClNOch(CH3)CO2CH2
3-1424-ClNOch(CH3)CO2CH2CH2
3-1434-ClNOch(CH3)CO2CH2CH2CH3
3-1444-ClNOch(CH3)CO2CH2CH2CH2CH3
3-1454-ClNOch(CH3)CO2CH(CH3)2
3-1464-ClNOch(CH3)CO2C(CH3)3
3-1474-ClNOch(CH3)CO2CH2CH2F
3-1484-ClNOch(CH3)CO2CH2CH2Cl
3-1494-ClNOch(CH3)CO2CH2CCl3
3-1504-ClNOch(CH3)CO2CH2CH=CH2

Connection # X3X4And
3-1514-ClNOch2CO2CH3
3-1524-ClNOch2CO2CH2CH3
3-1534-ClNOch2CO2CH2CH2CH3
3-1544-ClNOch2CO2CH2CH2CH2CH3
3-1554-ClNOch2CO2CH(CH3)2
3-1564-ClNOch2CO2C(CH3)3
3-1574-ClNOch2CO2CH2CH2F
3-1584-ClNOch2CO2CH2CH2Cl
3-1594-Cl Och2CO2CH2CCl3
3-1604-ClNOch2CO2CH2CH=CH2
3-161*NNNHCH(CH3)CO2CH3
3-162NNNHCH(CH3)CO2CH2CH3
3-163NNNHCH(CH2)CO2CH2CH2CH3
3-164NNNHCH(CH3)CO2CH2CH2CH2CH3
3-165NNNHCH(CH3)CO2CH(CH3)2
3-166NNNHCH(CH3)CO2C(CH3)3
3-167NNNHCH(CH3)CO2CH2CH2F
3-168NNNHCH(CH3)CO2CH2CH2Cl
3-169NNNHCH(CH3)CO2CH2CCl3
3-170NNNHCH(CH3)CO2CH2CH=CH2
3-171* NNNHCH2CO2CH3
3-172NNNHCH2CO2CH2CH3
3-173NNNHCH2CO2CH2CH2CH3
3-174NNNHCH2CO2CH2CH2CH2CH3
3-175NNNHCH2CO2CH(CH3)2

1H-NMR (CDCl3/400MHz) δ (ppm)

Connection 3-161: is 1.51 (d, 3H, J=8,8 Hz), 3,51 (d, 3H, J=1.2 Hz), 3,71 (s, 3H), 4,16 (DQC, 1H, J=8,8 Hz and 7.6 Hz), 4,63 (sm, 1H, J=7,6 Hz), of 6.31 (s, 1H), 6,6-6,7 (m, 2H), between 7.0 and 7.1 (m, 1H), 7,39 (d, 1H, J=9,2 Hz).

Connection 3-171: 3,52 (d, 3H, J=1.2 Hz), 3,63 (s, 3H), 4,11 (d, 1H, J=18,4 Hz and 7.6 Hz), 4,18 (d, 1H, J=18,4 Hz), 6,27 (s, 1H), 6,7-6,8 (m, 1H), 6,9-7,1 (m, 3H), 7,0-7,2 (m, 1H), 7,35 (d, 1H, J=8,8 Hz)

Connection # X3X4And
3-176NNNHCH2CO2C(CH3)3
3-177NNNHCH2CO2CH2CH2F
3-178NNNHCH2CO2CH2CH2Cl
3-179NNN2CO2CH2CCl3
3-180NNNHCH2CO2CH2CH=CH2
3-181NNN(CH3)CH(CH3)CO2CH3
3-182NNN(CH3)CH(CH3)CO2CH2CH3
3-183NNN(CH3)CH2CO2CH3
3-184NNN(CH3)CH2CO2CH2CH3
3-185NNN(CH3)CH2CO2CH2CH2CH3
3-186NNOCH(CH3)CO2CH2CH2CH=CH2
3-187NNOch(CH3)CO2CH2CH(CH3)2
3-188NNOch(CH3)CO2CH(CH3)CH2CH3
3-189NNOCH(CH3)CO2CH2CH2CH2CH2CH3
3-190 NNOCH(CH3)CO2CH2CH2CH(CH3)2
3-191NNOch(CH3)CO2CH2CH(CH3)CH2CH3
3-192NNOch(CH3)CO2CH(CH3)CH2CH2CH3
3-193NNOCH(CH3)CO2C(CH3)2CH2CH3
3-194NNOCH(CH3)CO2CH(CH3)CH(CH3)2
3-195NNOch(CH3)CO2CH2C(CH3)3
3-196NNOCH(CH3)CO2CH2With≡SN
3-197NNOch(CH3)CO2CH2CH2CH=CH2
3-198NNOch2CO2CH2CH(CH3)2
3-199NNOch2CO2CH(CH3)CH2CH3
3-200NNOch2CO2With the 2CH2CH2CH2CH3
3-201NNOch2CO2CH2With≡SN

The compound of the formula [I-4] (number of compounds described in table 4)

Table 4

Connection # X1X3X4A
4-1NO2HHOch(CH3)CO2N
4-2FHHOch(CH3)CO2N
4-3BrHHOch(CH3)CO2N
4-4CNHHOch(CH3)CO2N
4-5NO2HHOch(CH3)CO2CH3
4-6BrHHOch(CH3)CO2CH3
4-7CNHHOch(CH3)CO2CH3
4-8NO2H HOch(CH3)CO2CH2CH3
4-9F4-CH3HOch(CH3)CO2CH2CH3
4-10CNHHOch(CH3)CO2CH2CH3
4-11BrHHOch(CH3)CO2CH2CH2CH3
4-12CN4-CH3HOch(CH3)CO2CH2CH2CH3
4-13NO25-CH3HOch(CH3)CO2CH2CH2CH2CH3
4-14CNHHOch(CH3)CO2CH2CH2CH2CH3
4-15NO2HHOch2CO2N
4-16FHHOch2CO2N
4-1 7BrHHOch2CO2N
4-18CNHHOch CO2N
4-1 9NO2HHOch2CO2CH3
4-20FHHOch2CO2CH3
4-21BrHHOch2CO2CH3
4-22CNHHOch2CO2CH3
4-23CN4-CH3HOch2CO2CH3
4-24NO25-CH3HOch2CO2CH3
4-25NO2HHOch2CO2CH2CH3

Connection # X1X3X4A
4-26FHHOch2CO2CH2CH3
4-27BrHHOch2CO2CH2CH3
4-28CNH HOch2CO2CH2CH3
4-29NO24-CH3HOch2CO2CH2CH3
4-30CN4-CH3HOch2CO2CH2CH3
4-31NO25-CH3HOch2CO2CH2CH3
4-32CN5-CH3HOch(CH3)CO2CH3
4-33NO2HHOch2CO2CH2CH2CH3
4-34CNHHOch2CO2CH2CH2CH3
4-35NO2HHOch2CO2CH2CH2CH2CH3
4-36CNHHOch2CO2CH2CH2CH2CH3

The compound of the formula [I-5] [numbers of the compounds described in table 5

Table 5

Connection # X1X3X4A
5-1NO2HHOch(CH3)CO2N
5-2FHHOch(CH3)CO2N
5-3BrHHOch(CH3)CO2N
5-4CNHHOch(CH3)CO2N
5-5NO2HHOch(CH3)CO2CH3
5-6BrHHOch(CH3)CO2CH3
5-7CNHHOch(CH3)CO2CH3
5-8NO2HHOch(CH3)CO2CH2CH3
5-9F4-CH3HOch(CH3)CO2CH2CH3
5-10CNHHOch(CH3)CO CH2CH3
5-11BrHHOch(CH3)CO2CH2CH2CH3
5-12CN4-CH3HOch(CH3)CO2CH2CH2CH3
5-13NO25-CH3HOch(CH3)CO2CH2CH2CH2CH3
5-14CNHHOch(CH3)CO2CH2CH2CH2CH3
5-15NO2HHOch2CO2N
5-16FHHOch2CO2N
5-17BrHHOch2CO2N
5-18CNHHOch2CO2N
5-19NO2HHOch2CO2CH3
5-20FHHOch2CO2CH3
5-21BrH/td> HOch2CO2CH3
5-22CNHHOch2CO2CH3
5-23CN4-CH3HOch2CO2CH3
5-24NO25-CH3HOch2CO2CH3
5-25NO2HHOch2CO2CH2CH3

Connection # X1X3X4A
5-26FHHOch2CO2CH2CH3
5-27BrHHOch2CO2CH2CH3
5-28CNHHOch2CO2CH2CH3
5-29NO24-CH3HOch2CO2CH2CH3
5-30CN4-CH3HThe CH 2CO2CH2CH3
5-31NO25-CH3HOch2CO2CH2CH3
5-32CN5-CH3HOch(CH3)CO2CH3
5-33NO2HHOch2CO2CH2CH2CH3
5-34CNHHOch2CO2CH2CH2CH3
5-35NO2HHOch2CO2CH2CH2CH2CH3
5-36CNHHOch2CO2CH2CH2CH2CH3

The following shows some typical intermediate products are applicable for producing compounds of the present invention. These intermediate products are described by a combination of the formulas described below with Panamera, which determines the combination of the substituents shown in table 6. (For example, the intermediate compound A1-1 is a compound having the General formula [A1], in which the substituents X1X2and And are the deputies, is written in Panamera 1 in table 6).

The compound of the formula [A1]

The compound of the formula [A2]

The compound of the formula [A3-]

The compound of the formula [A4]

The compound of the formula [A5-]

The compound of the formula [A6]

The compound of the formula [A7-]

The compound of the formula [A8-]

The compound of the formula [A9]

The compound of the formula [a10-]

The compound of the formula [A11-]

The compound of the formula [A12-

Table 6
PonomarX1X2And
1ClFOch3
2ClFOch3CH3
3ClFOch(CH3)2
4ClFHE
5ClFAbout the H 2Ph
6ClFOch(CH3)CO2N
7ClFOch(CH3)CO2CH3
8ClFOch(CH3)CO2CH2CH3
9ClFOch(CH3)CO2CH2CH=CH2
10ClFOch(CH3)CO2CH3CH2CH2CH3
11ClFOch(CH3)CO2CH(CH3)2
12ClFOch(CH3)CO2CH2CH(CH3)2
13ClFOch(CH3)CO2CH(CH3)CH2CH3
14ClFOCH(CH3)CO2CH2CH2CH2CH2CH3
15ClFOch(CH3)CO2CH2CH2CH(CH3)2
16ClFOch(CH3)CO2CH2CH(CH3)CH2CH3
17ClFOch(CH3)CO2CH(CH3)CH2CH2CH3
18ClFOCH(CH3)CO2CH(CH3)CH(CH3)2
19ClFOCH(CH3)CO2CH2C(CH3)3
20ClFOch(CH3)CO2CH3With≡SN
21ClFOch2CO2N
22ClFOch2CO2CH3
23ClFOch2CO2CH2CH3
24ClFOch2CO2CH2CH=CH2

Br
PonomarX1X2A
25ClFOch2CO2CH2CH2CH2CH3
26ClFOch(CH3)CO2CH(CH3)2
27ClFOch(CH3 2CH2CH(CH3)2
28ClFOch(CH3)CO2CH(CH3)CH2CH3
29ClFOch(CH3)CO2CH2CH2CH2CH2CH3
30ClFOch(CH3)CO2CH2CH2CH(CH3)2
31ClFOch(CH3)CO2CH2CH(CH3)CH2CH3
32ClFOch(CH3)CO2CH(CH3)CH2CH2CH3
33ClFOch(CH3)CO2CH(CH3)CH(CH3)2
34ClFOch(CH3)CO2CH2C(CH3)3
35ClFOch(CH3)CO2CH2C=CH
36BrFOch3
37BrFOch2CH3
38BrFOch(CH3)2
39FOH
40BrFOch2Ph
41BrFOch(CH3)CO2N
42BrFOch(CH3)CO2CH3
43BrFOch(CH3)CO2CH2CH3
44BrFOch(CH3)CO2CH2CH=CH2
45BrFOCH(CH3)CO2CH2CH2CH2CH3
46BrFOch(CH3)CO2CH(CH3)2
47BrFOch(CH3)CO2CH2CH(CH3)2
48BrFOch(CH3)CO2CH(CH3)CH2CH3
49BrFOCH(CH3)CO2CH2CH2CH2CH2CH3

/tr>
PonomarX1X2A
50FOch(CH3)CO2CH2CH2CH(CH3)2
51BrFOch(CH3)CO2CH2CH(CH3)CH2CH3
52BrFOCH(CH3)CO2CH(CH3)CH2CH2CH3
53BrFOCH(CH3)CO2CH(CH3)CH(CH3)2
54BrFOch(CH3)CO2CH2C(CH3)3
55BrFOch(CH3)CO2CH2With≡SN
56BrFOCH2CO2H
57BrFOch2CO2CH3
58BrFOch2CO2CH2CH3
59BrFOch2CO2CH2CH=CH2
60BrFOch2CO2CH2CH2CH2CH3
61BrFOch(CH3)CO2The n(CH 3)2
62BrFOCH(CH3)CO2CH2CH(CH3)2
63BrFOch(CH3)CO2CH(CH3)CH2CH3
64BrFOch(CH3)CO2CH2CH2CH2CH2CH3
65BrFOCH(CH3)CO2CH2CH2CH(CH3)2
66BrFOch(CH3)CO2CH2CH(CH3)CH2CH3
67BrFOch(CH3)CO2CH(CH3)CH2CH2CH3
68BrFOch(CH3)CO2CH(CH3)CH(CH3)2
69BrFOch(CH3)CO2CH2C(CH3)3
70BrFOch(CH3)CO2CH2With≡SN
71NO2FOch3
72NO2FOch2CH3
73NO2FOCH(CH3)2
74NO2FOH

Och3
PonomarX1X2A
75NO2FOch2Ph
76NO2FOch(CH3)CO2N
77NO2FOch(CH3)CO2CH3
78NO2FOch(CH3)CO2CH2CH3
79NO2FOch(CH3)CO2CH2CH=CH2
80NO2FOch2CO2N
81NO2FOch2CO3CH3
82NO2FOch2CO2CH2CH3
83NO2FOch2CO2CH2CH=CH2
84CNF
85CNFOch2CH3
86CNFOch(CH3)2
87CNFOH
88CNFOch2Ph
89CNFOch(CH3)CO2N
90CNFOch(CH3)CO2CH3
91CNFOch(CH3)CO2CH2CH3
92CNFOch(CH3)CO2CH2CH=CH2
93CNFOch2CO2N
94CNFOch2CO2CH3
95CNFOch2CO2CH2CH3
96CNFOch2CO2CH2CH=CH2

Here are examples of the preparation of these compounds. In these examples, the compounds shown as Compound No. in tables 1-5 and "part (s)" designation shall indicate the part (s) by weight".

Sample preparation 1

Fifty (50) parts of each of these compounds 1-1 - 1-201, 2-1 - 2-201, 3-1 - 3-201, 4-1 - 4-36 and 5-1 - 5-36, 3 parts ligninsulfonate calcium, 2 parts of sodium lauryl and 45 parts of synthetic hydrated silicon dioxide are well pulverized and mixed to obtain each of the wettable powders.

Example preparation of 2

Ten (10) parts of each of these compounds 1-1 - 1-201, 2-1 - 2-201, 3-1 - 3-201, 4-1 - 4-36 and 5-1 - 5-36, 14 parts steelfinish of polyoxyethylene ether, 6 parts of dodecylbenzenesulfonate calcium, 35 parts of xylene and 35 parts of cyclohexanone are mixed with the receipt of each of the emulsifiable concentrates.

Example preparation of 3

Two (2) parts of each of these compounds 1-1 - 1-201, 2-1 - 2-201, 3-1 - 3-201, 4-1 - 4-36 and 5-1 - 5-36, 2 parts of synthetic hydrated silicon dioxide, 2 parts ligninsulfonate calcium, 30 parts of bentonite and 64 parts of kaolin clay are well pulverized and mixed, and after adding water and intensive mixing, granularit and dried to obtain each of these granules.

Example preparation of 4

Twenty-five (25) parts of each of these compounds 1-1 - 1-201, 2-1 - 2-201, 3-1 - 3-201, 4-1 - 4-36 and 5-1 - 5-36, 50 parts of 10% aqueous solution of polyvinyl alcohol and 25 parts of water are mixed, pulverized by a wet method to an average particle diameter of 5 μm or less to obtain each is of flowable wettable powders.

Example preparation of 5

Five (5) parts of each of these compounds 1-1 - 1-201, 2-1 - 2-201, 3-1 - 3-201, 4-1 - 4-36 and 5-1 - 5-36 added to 40 parts of 10% aqueous solution of polyvinyl alcohol and the mixture emuleret and dispersed by a homogenizer until the average particle diameter of 10 μm or less. Then to the resulting mixture of 55 parts of water to obtain each of the concentrated emulsion.

Here are examples of tests that demonstrate that these compounds are effective as an active ingredient of the herbicide. In the examples of each of these compounds is shown as Compound No. in tables 1-5.

The test example 1

Cylindrical plastic vessel having a diameter of 10 cm and a depth of 10 cm were filled with soil and then seeded with morning glory zelenolistnoe (Ipomoea hederacea), kineticom Theophrastus (Abutilon theophracti), barnyard grass-batusim millet (Echinochloa crus-galli) and Alopecurus myservername (Aloprcurus myosuroides). These test plants were grown in the greenhouse for 9 days. Then each of the compounds 1-1, 2-1, 3-1, 3-2, 3-11, and 3-12 prepared in the form of an emulsifiable concentrate according to the example of preparation 2 and then diluted to the prescribed amount with water containing a spreading agent, and the diluted drug was uniformly sprayed on the foliage of the test plants with a sprayer at a dose of 1000 liters per hectare. After application, the test plants expressed ivali in the greenhouse for 7 days and identified herbicide activity of the applied composition. In the result, it was determined that the growth ipomea zelenolistnoe, cantica Theophrastus, barnyard grass-batoshevo millet and Alopecurus myservicename was completely suppressed when applying the compounds 1-1, 2-1, 3-1, 3-2, 3-11, and 3-12 in the dose of 125 g/ha, respectively.

The test example 2

Cylindrical plastic vessel having a diameter of 10 cm and a depth of 10 cm were filled with soil and then seeded with morning glory zelenolistnoe (Ipomoea hederacea), kineticom Theophrastus (Abutilon theophracti) and barnyard grass-batusim millet (Echinochloa crus-galli). Then each of the compounds 1-1, 2-1 and 3-1 was prepared in the form of an emulsifiable concentrate according to the example of preparation 2 and then diluted to the prescribed amount with water and dilute the drug was uniformly sprayed on the soil surface sprayer at a dose of 1000 liters per hectare. After application, the test plants were grown in the greenhouse for 7 days and identified herbicide activity of the applied composition. The emergence of ipomea zelenolistnoe, cantica Theophrastus and barnyard grass-batoshevo millet was completely suppressed when applying the compounds 1-1, 2-1 and 3-1 in the dose of 500 g/ha, respectively.

The test example 3

Cylindrical plastic vessel having a diameter of 10 cm and a depth of 10 cm were filled with soil and then seeded with morning glory zelenolistnoe (Ipomoea hederacea), kineticom Theophrastus (Abutilon theophracti) and barnyard grass-batusim millet (Echinochloa crusgalli). These test plants were grown in the greenhouse for 9 days. After that, each of the compounds 3-16, 3-20 and 3-198 prepared in the form of an emulsifiable concentrate according to the example of preparation 2 and then diluted to the prescribed amount with water containing a spreading agent, and the diluted drug was uniformly sprayed on the foliage of the test plants with a sprayer at a dose of 1000 liters per hectare. After application, the test plants were grown in the greenhouse for 7 days and identified herbicide activity. In the result, it was determined that the growth ipomea zelenolistnoe, cantica Theophrastus and barnyard grass-batoshevo millet was completely suppressed when applying compounds 3-16, 3-20 and 3-198 at a dose of 500 g/ha, respectively.

The test example 4

Cylindrical plastic vessel having a diameter of 10 cm and a depth of 10 cm were filled with soil and then seeded with morning glory (Echinochloa crus-galli) and Alopecurus myservername (Alopecurus myosuroides). Then each of the connections, 3-2, 3-11, 3-12, 3-16, 3-20 and 3-198 prepared in the form of an emulsifiable concentrate according to the example of preparation 2 and then diluted to the prescribed amount with water and dilute the drug was uniformly sprayed on the soil surface sprayer at a dose of 1000 liters per hectare. After application, the test plants were grown in the greenhouse for 7 days and identified herbicide activity caused compositions Emergence of ipomea zelenolistnoe, cantica Theophrastus, barnyard grass-batoshevo millet and Alopecurus myservicename was completely suppressed at drawing connections 3-2, 3-11, 3-12, 3-16, 3-20 and 3-198 dose of 2000 g/ha, respectively.

The test example 4A

Cylindrical plastic vessel having a diameter of 10 cm and a depth of 10 cm were filled with soil and then seeded with morning glory zelenolistnoe (Ipomoea hederacea), kineticom Theophrastus (Abutilon theophracti), barnyard grass-batusim millet (Echinochloa crus-galli) and Alopecurus myservername (Alopecurus myosuroides). Then each of the plants were germinated in the greenhouse for 9 days. Then each of the compounds 3-161 and 3-171 prepared in the form of an emulsifiable concentrate according to the example of preparation 2 and then diluted to the prescribed amount with water and dilute the drug was uniformly sprayed on the soil surface sprayer at a dose of 1000 liters per hectare. After application, the test plants were grown in a greenhouse for 16 days and was determined herbicide activity of the applied composition. The emergence of ipomea zelenolistnoe, cantica Theophrastus and barnyard grass-batoshevo millet was completely suppressed when applying connection 3-161 at a dose of 125 g/ha Emergence of ipomea zelenolistnoe, cantica Theophrastus, barnyard grass-batoshevo millet and Alopecurus the bat-hvostichenko was completely suppressed when applying connection 3-171 at a dose of 125 g/ha

In the following the existing examples of tests of herbicide activity was assessed with 11 levels index 0-10, i.e. marked digits"0", "1", "2", "3", "4", "5", "6", "7", "8", "9" or "10"where "0" means that there was no difference or a small difference in the degree of germination or growth between treated and untreated subjects plants during the test, and "10" means that the test plants were completely killed or germination or growth is completely inhibited.

Table 7
AWO 98/41093
BWO 97/01541
CWO 97/01541

Example test 5

Cylindrical plastic vessel having a diameter of 18.5 cm and a depth of 15 cm were filled with soil and then seeded with starry average (Stellaria media). These test plants were grown in the greenhouse for 29 days. After that, each of compounds 1-2 and Compounds As prepared in the form of emulsifiable concentrate in accordance with the example of preparation 2 and then diluted to the prescribed amount with water containing a spreading agent, and the diluted drug was uniformly sprayed on the foliage of the test plants with a sprayer at a dose of 1000 l on GE is tar. After application, the test plants were grown in the greenhouse for 9 days and was determined herbicide activity. These results are shown in the following table 8.

Table 8
Connection # Dose (g/ha)Herbicide activity
1-21010
And105

Example test 6

Plastic vessel (27 cm × 19 cm × 7 cm) were filled with soil and then planted jonssonova grass (Sorghum Halepense), spickle giant (Setaria faberi), perushim millet (Echinochloa crus-galli), weed blood (Digitaria sanguinalis), vyvance broadleaf (Brachiaria platyphylla) and wild oat (Avena fatua). These subjects plants were grown in the greenhouse for 25 days. After that, each of compounds 3-11, 4-22, b and C were prepared in the form of emulsifiable concentrate in accordance with the example of preparation 2 and then diluted to the prescribed amount with water containing a spreading agent, and the diluted drug was uniformly sprayed on the foliage of the test plants with a sprayer at a dose of 1000 liters per hectare. After application, the test plants were grown in the greenhouse for 4 days and was determined herbicide activity. These results are shown in the following table 9. (Table 9 subjects R is stenia shown as follows. Jonssonova grass: J, Alopecurus giant: GF, plushie millet: In, weed blood: LC, Vatanka broadleaf: sun, wild oat (empty oat): W.).

Table 9
Connection # Dose (g/ha)Herbicide activity
JGFInLCSUW
3-113.310910101010
19989910
0.33887888
4-223.391099910
1889989
0.33878988
In3.3777887
1 756765
0.33232322
3.3646565
1434333
0.33211221

1. A derivative of uracil of the formula [I]

where W represents oxygen, sulfur or imino;

Y denotes oxygen or sulfur;

R1represents C1-C3-alkyl or C1-C3-halogenated;

R2represents C1-C3-alkyl; R4denotes hydrogen or methyl;

R5represents C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil or3-C6-halogenoalkanes;

X1denotes halogen, cyano or nitro;

X2denotes hydrogen or halogen and

each of X3and X4independently denotes hydrogen, halogen, C 1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes,1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenoalkane,1-C6-alkoxycarbonyl-C1-C6-alkoxy or cyano.

2. A derivative of uracil according to claim 1, where X1denotes halogen and X2denotes halogen.

3. A derivative of uracil according to claim 1 or 2, where X1denotes chlorine.

4. A derivative of uracil according to claims 1, 2 or 3, where X2denotes fluorine.

5. A derivative of uracil according to any one of claims 1 to 4, where W is in ortho-position on the benzene ring relative to Y.

6. A derivative of uracil according to any one of claims 1 to 5, where W is oxygen.

7. A derivative of uracil according to any one of claims 1 to 6, where R1denotes methyl or trifluoromethyl.

8. A derivative of uracil according to any one of claims 1 to 7, where R2denotes methyl.

9. A derivative of uracil according to any one of claims 1 to 8, wherein X3and X4denote hydrogen.

10. A derivative of uracil according to any one of claims 1 to 9, where R5denotes methyl or ethyl.

11. Herbicide composition that contains uracil derivative according to any one of claims 1 to 10, and an inert carrier or diluent.

12. The method of suppressing the growth of weeds, including the application of eff is active amount of uracil derivative according to any one of claims 1 to 10 in the weeds or on the place, where the weeds grow or will grow.

13. A derivative of uracil according to any one of claims 1 to 10 as a herbicide.

14. A derivative of uracil of the formula [VII]

where W represents oxygen, sulfur or imino;

Y denotes oxygen or sulfur;

R1represents C1-C3-alkyl or C1-C3-halogenated;

R2represents C1-C3-alkyl;

R4denotes hydrogen or methyl;

X1denotes halogen, cyano or nitro;

X2denotes hydrogen or halogen and

each of X3and X4independently denotes hydrogen, halogen, C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes, C1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenoalkane, C1-C6-alkoxycarbonyl-C1-C6-alkoxy or cyano.

15. A derivative of uracil at 14, where W is in ortho-position on the benzene ring relative to Y.

16. Derived aniline of the formula [XXXII]

where W represents oxygen;

R17denotes oxygen;

R4about the means hydrogen or methyl;

R5represents C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes;

X1denotes halogen, cyano or nitro;

X2denotes hydrogen or halogen and

each of X3and X4independently denotes hydrogen, halogen, C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes,1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenoalkane,1-C6-alkoxycarbonyl-C1-C6-alkoxy or cyano.

17. A derivative of uracil in clause 16, where W is in ortho-position on the benzene ring relative to R17.

18. Methyl-[2-(5-amino-2-chloro-4-pertenece)phenoxy]acetate.

19. Ethyl-[2-(5-amino-2-chloro-4-pertenece)phenoxy]acetate.

20. The compound of the formula [XXXIV]

where W represents oxygen;

R17denotes oxygen;

R4denotes hydrogen or methyl;

R5represents C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3 6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes;

R18represents C1-C6-alkyl or phenyl;

X1denotes halogen, cyano, nitro;

X2denotes hydrogen or halogen and

each of X3and X4independently denotes hydrogen, halogen, C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes, C1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenoalkane, C1-C6-alkoxycarbonyl-C1-C6-alkoxy or cyano.

21. A derivative of uracil in claim 20, where W is in ortho-position on the benzene ring relative to R17.

22. The compound of the formula [XXXIII]

where W represents oxygen;

R17denotes oxygen;

R4denotes hydrogen or methyl;

R5represents C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes;

X1denotes halogen, cyano or nitro;

X2indicates water is od or halogen and

each of X3and X4independently denotes hydrogen, halogen, C1-C6-alkyl, C1-C6-halogenated,3-C6alkenyl,3-C6-halogenoalkanes,3-C6-quinil,3-C6-halogenoalkanes,1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenoalkane,1-C6-alkoxycarbonyl-C1-C6-alkoxy or cyano.

23. A derivative of uracil on p.22, where W is in ortho-position on the benzene ring relative to R17.

24. A derivative of uracil according to claim 1, where R1represents trifluoromethyl, R2denotes methyl, R4denotes hydrogen, R5denotes methyl, X1denotes chlorine, X2denotes fluorine, X3denotes hydrogen, X4denotes hydrogen, W represents oxygen, Y represents oxygen, and W is in ortho-position on the benzene ring relative to Y.

25. A derivative of uracil according to claim 1, where R1represents trifluoromethyl, R2denotes methyl, R4denotes hydrogen, R5denotes ethyl, X1denotes chlorine, X2denotes fluorine, X3denotes hydrogen, X4denotes hydrogen, W represents oxygen, Y represents oxygen, and W is in ortho-position on the benzene ring relative to Y.

Priority items:

07.12.1999 claims 1 to,14, 16, 20, 22;

02.06.2000 PP, 19.



 

Same patents:

The invention relates to substituted acylaminoalkyl-brazilan General formula I

where n is 0 or 1; And is unsubstituted or substituted alcander; Ar is a substituted aryl or unsubstituted or substituted heterocyclyl an oxygen atom, Q is a group-O-, R1is unsubstituted or substituted alkyl, R2is unsubstituted or substituted alkyl, R3is hydrogen, R4or R5- independently of each other cyano or halogen, R6- alkylsulfonyl; the herbicide agent containing at least one substituted acylaminoalkyl-uracil and conventional fillers

The invention relates to an improved process for the preparation of compounds of formula (I), where each of the residues X and Y independently of one another denotes hydrogen, halogen, (C1-C4)-alkyl, (C1-C4)-alkoxygroup or (C1-C4)-allylthiourea, each of the last three residues is unsubstituted or substituted by one or more residues from the group comprising halogen, (C1-C4)-alkoxygroup or (C1-C4)-allylthiourea, means or di[(C1-C4)alkyl]-amino, (C3-C6-cycloalkyl, (C3-C5)-alkenyl, (C3-C5)-quinil, (C3-C5)-alkenylacyl or (C3-C5)-alkyloxy, in which the compound of formula (II) or salts thereof, where X and Y are specified in the formula (I) values are subjected to interaction with 1-6 moles of phosgene per 1 mol of the compounds of formula (II) in the presence of 2-3,5 molar equivalents of an organic aminoaniline per mole of the compounds of formula (II) and in the presence of an aprotic organic solvent at the reaction temperature in the range from -30 to +60oWith

The invention relates to new derivatives of phenylsulfonylacetate General formula (I), which are herbicide and regulating plant growth properties and can find application in agriculture

The invention relates to an improved process for the preparation of 6-substituted orallow General formula I, where R = CH3WITH6H5CH2, 2,6-F2WITH6H3CH2that can be used in the pharmaceutical industry to obtain drugs

The invention relates to new 6-(3-acetylphenyl)aminouracil formula I, which stimulates the immune system and antiviral properties and can be used in the treatment of viral diseases caused by chlamydia, as well as diseases caused by immunodeficiency, in particular malignant tumors, and also in veterinary medicine

The invention relates to the field of synthesis and technology of obtaining 6-methyluracil-5-sulfochloride promising starting material for the production of medical preparations and dyes

The invention relates to a new group of individual compounds of General formula I

< / BR>
where R denotes cyclopropyl, cyclobutyl, cyclohexyl, phenyl, unsubstituted or mono -, di - or tizamidine group selected from hydroxy, C1-C4of alkyl, C1-C4alkoxy, halogen, trifloromethyl, ceanography and amino groups; 1-or 2-naphthyl, 9-anthracene; 2-anthrachinone, Persil, unsubstituted or substituted group selected from1-C4of alkyl, C1-C4alkoxy, ceanography and halogen; 2-, 3 - or 4-chinoline, oxiranyl, 1-benzotriazolyl, 2-benzoxazolyl, furanyl, substituted C1-C4alkoxycarbonyl; C1-C4alkylsulphonyl or benzoyl; R1denotes halogen or1-C4alkyl, R2and R3independently represent hydrogen or C1-C4alkyl; X denotes an oxygen atom and Y represents an oxygen atom, a sulfur atom or a carbonyl, or their pharmaceutically acceptable salts, method of production thereof and pharmaceutical composition having antiviral activity, containing antiviruse-effective amount of compounds of General formula I

The invention relates to novel 2,4-dioxo-5-arylidene-1,3-pyrimidines of General formula I, where R is independently selected from the group: H, HE, lowest alkoxyl, halogen, nitro, di(lower)alkylamino, n = 1-3, or two adjacent R along the benzene ring to which they are attached, when n = 2, 4 form a benzo, and dibenzo when n = 2 form a 3,4-dioxolane ring

The invention relates to new pyrimidine derivative or its pharmaceutically acceptable salts, pharmaceutical composition having the effect of inhibitor endothelin and method of prevention and treatment of diseases induced endothelium, particularly diseases associated with circulatory disorders such as hypertension, hypertension, asthma, angina, etc

The invention relates to new derivatives of sulfonylurea of the formula I, where R1group CO-Q-R5; R2is hydrogen, alkyl with 1-4 carbon atoms, alkoxy with 1-4 carbon atoms; R3- alkylsulfonyl with 1 to 4 carbon atoms, monoalkylbenzenes with 1-4 carbon atoms or dialkylaminoalkyl with 1-4 carbon atoms in each alkyl part, alkylsulphonyl with 1-6 carbon atoms in the alkyl part, with the alkyl part can be single or multiply substituted with halogen, alkoxygroup with 1-4 carbon atoms, phenylcarbinol, phenylsulfonyl, phenyl residue which may be substituted by alkyl with 1 to 4 carbon atoms, formyl group of the formula-CO-CO-R1where R1means alkoxy with 1-4 carbon atoms, cycloalkylcarbonyl with 3-6 carbon atoms in cycloalkyl part, a group of the formula

< / BR>
moreover, if the group-CH2-NR2R3located in the para-position relative to the group of SO2the rest of the sulfonylureas, R3does not mean the unsubstituted alkylsulphonyl with 1-6 carbon atoms in the alkyl part, R2and R3together mean a group of the formula (CH2)m- Or-B1-(CH2)m1-B-, where b and b9-, T -, an oxygen atom or sulfur, R4is hydrogen or methyl, R5is hydrogen, alkyl with 1-4 carbon atoms, R6is alkyl with 1-4 carbon atoms, R7and R8independently from each other hydrogen or alkyl with 1-4 carbon atoms, unsubstituted or multiply substituted with halogen, R9is alkyl with 1-4 carbon atoms And is a group of the formula below, where Z is - CH= or-N=, one of the radicals X and Y represents hydrogen, halogen, alkyl or alkoxy with 1-3 carbon atoms, unsubstituted or substituted by halogen atoms and the other radical X or Y means hydrogen, alkyl or alkoxy with 1-3 carbon atoms, unsubstituted or substituted by halogen atoms, mono - or dialkylamino with 1-3 carbon atoms in each alkyl group, or their salts

The invention relates to new derivatives and analogs 3-arylpropionic acid having the General formula (I), and their stereo and optical isomers and racemates, as well as their pharmaceutically acceptable salts, wherein in the formula And is located in the meta - or para-position and represents a

where: R represents hydrogen;

-ORawhere Rarepresents hydrogen, alkyl, phenyl or alkylphenyl;

-NRaRbwhere Raand Rbare the same or different and represent hydrogen, alkyl, phenyl, alkylphenyl, cyano;

R1represents alkyl, cyano;

-ORewhere Rerepresents alkyl, phenyl or alkylphenyl;

-O-(CH2]m-ORfwhere Rfrepresents alkyl, and m is an integer of 1-2;

-SRdwhere Rdrepresents an alkyl or phenyl;

-SO2ORawhere Rarepresents alkyl, phenyl or alkylphenyl;

-COORdwhere Rdrepresents alkyl;

R2represents hydrogen or alkyl;

R3and R4

D is situated in the ortho-, meta - or para-position and represents a

-OSO2Rdwhere Rdrepresents alkyl, phenyl or alkylphenyl;

-OCONRfRawhere Rfand Rarepresent hydrogen, alkyl, phenyl or alkylphenyl;

-NRcCOORdwhere Rcrepresents hydrogen or alkyl and Rdrepresents alkyl, phenyl or alkylphenyl;

-NRcCORawhere Rcrepresents hydrogen or alkyl, and Rarepresents hydrogen, alkyl, phenyl or alkylphenyl;

-NRcRdwhere Rcand Rdrepresent hydrogen, alkyl, phenyl or alkylphenyl;

-NRcSO2Rdwhere Rcrepresents hydrogen or alkyl, and Rdrepresents alkyl, phenyl or alkylphenyl;

-NRcCONRaRkwhere Rcrepresents hydrogen, Raand Rkare the same or different and each represents hydrogen, alkyl, phenyl or alkylphenyl;

-NRcCSNRaRkwhere Rcrepresents hydrogen, Raand Rkare the same or different and each represents hydrogen, phenyl иLASS="ptx">-SRcwhere Rcrepresents alkyl, phenyl or alkylphenyl;

-SO2ORawhere Rarepresents alkyl, phenyl or alkylphenyl;

-CN;

-CONRcRawhere Rcrepresents hydrogen or alkyl, and Rarepresents hydrogen or alkyl;

D’ is located in the meta-position and represents-ORfwhere Rfrepresents alkyl; or is located in the ortho-, meta - or para-position and represents hydrogen;

D’ is located in the ortho - or para-position and represents-NO2, -ORfwhere Rfrepresents alkyl; or is located in the ortho-, meta - or para-position and represents hydrogen;

where specified, the alkyl means a straight or branched alkyl group having from 1 to 6 carbon atoms, or cyclic alkyl having from 3 to 6 carbon atoms, with the specified alkyl may be substituted by one or more than one group of alkyl, alkoxy, halogen or phenyl; where the specified phenyl may be substituted by one or more than one group of alkyl, alkoxy, nitro, thiol, or halogen; the invention also relates to a method of their production, pharmaceutical preparations containing them, the Sabbath.

The invention relates to new compounds of formula (1) or their pharmaceutically acceptable salts, where R1a, R2a, R3aand R4arepresent, each independently, hydrogen, hydroxyl, C1-C6alkyl, C1-C6alkoxy, benzyloxy, acetoxy, trifluoromethyl or halogen, and R5aand R6arepresent, each independently, tert-butoxycarbonyl, benzyloxycarbonyl, p-methoxybenzenesulfonyl or p-bromobenzyloxycarbonyl, which is an intermediate compound for the synthesis of benzimidazole derivatives and their pharmaceutically acceptable salts exhibiting excellent hypoglycemic effect

The invention relates to new modifications of 2-amino-4-(4-forbindelsen)-1-etoxycarbonyl-aminobenzoyl formula I

< / BR>
methods for their preparation and their use in pharmaceutical compositions

The invention relates to new derivatives of carbamino acid of General formula 1, where R1and R2independently of one another denote alkyl, aryl, aralkyl, heteroaryl, cycloalkyl or heterocyclyl, R3and R4independently of one another denote hydrogen, alkyl, halogen, hydroxyl or aryl, R5means-COOR6, R6denotes hydrogen or alkyl, And indicates alkylen or albaniles, denotes-O(CH2)m- or -(CH2)n-, m denotes an integer from 1 to 8, inclusive, n represents an integer from 0 to 8, inclusive, or their racemates, or individual isomers, or their new pharmaceutically acceptable salt, or solvate

The invention relates to the use of fluorinated derivatives of carbamino acid, namely polyfluoroankyl-N-arylcarbamates General formula

< / BR>
where R and R' = H, o-, m-or p-alkyl (C1-C3, CF3CH3S, Cl, NO2, NHCOOCHR"R"';

R" = H, CF3;

R"' = CF3, (CF2)nH, where n = 2-6, or-CF2NO2except 2.2-debtor-2-nitroethyl-N-phenylcarbamate, 2.2.2-triptorelin-N-p-nitrophenylacetate,

possessing antimicrobial activity

The invention relates to new visakapatnam the tritium substituted the carbamates of the formula R-NH-CO-OR1(I) where R is m-aminoacetophenone, when R1represents isopropyl, or R represents 3-(dimethylamino)-propyl, when R1is propyl

The invention relates to methods of producing alkyl-N-arylcarbamates, which use, for example, as starting materials for the production of isocyanates, pesticides, etc

The invention relates to new tricyclic derivative of the formula (I), (Ia'), (Ib'), (Ig'), (If'), their salts and hydrates, which have immunosuppressive or anti-allergic activity, pharmaceutical compositions based on these compounds and to a method of suppressing immune response or treatment and/or prevention of allergic diseases
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