Sulfonamide derivatives, method for their preparing and method for weed eradication

FIELD: organic chemistry, chemical technology, herbicides, agriculture.

SUBSTANCE: invention relates to new sulfonamides of the formula (I):

and their salt wherein A represents substituted or unsubstituted benzene ring or 5-membered, or 6-membered substituted or unsubstituted heteroaromatic ring taken among the group comprising thienyl, pyrazolyl, imidazolyl, pyridyl wherein optional substitutes are taken among the group consisting of halogen atom, substituted or unsubstituted (C1-C4)-alkyl, unsubstituted or substituted (C1-C4)-alkoxy-group, nitro-group, phenyl, phenoxy-group, benzoyl and (C1-C4)-alkylcarboxylate when any alkyl fragment in the latter indicated substituted is substituted with one or some halogen atoms, (C1-C4)-alkoxy-groups, cyano-group and phenyl; Q represents -O-, -S- or group of the formula: -CXX' wherein X and X' can be similar or different and each represents hydrogen atom, halogen atom, cyano-group, alkyl comprising 1-8 carbon atoms, or the group -ORa, -SRa; or one of X and X' represents hydroxy-group and another has values determine above; Ra means (C1-C8)-alkyl, phenyl; Rb means (C1-C8)-alkyl, phenyl; Y means nitrogen atom or the group CR9; R1 means unsubstituted (C1-C8)-alkyl or that substituted with halogen atom, cyano-group, phenyl or (C1-C4)-alkoxycarbonylamino-group, or it represents phenyl; R2 means hydrogen atom (H), (C1-C4)-alkyl; R3 and R4 can be similar or different and each represents (C1-C4)-alkyl, (C1-C4)-alkoxy-group, halogen atom; R9 means hydrogen atom (H) under condition that when Q represents oxygen atom (O) or -S- then ring A represents 5-membered substituted or unsubstituted heteroaromatic ring and determined above. Compounds of the formula (I) possess the herbicide activity that allows their using for eradication of weeds. Also, invention describes a method for preparing compounds of the formula (I).

EFFECT: improved preparing method, valuable properties of compounds.

9 cl, 5 tbl, 18 ex

 

The present invention relates to herbicide sulfonamides, processes for their preparation and preparative forms based on them.

In patent EP No. 323040 and WO No. 91/10653 disclosed herbicide sulfonamides, related to the compounds of the present invention.

One of the objects of the present invention are new sulfonamides of the formula:

and their salts, where

And represents a substituted or unsubstituted benzene ring, or a 5-membered substituted or unsubstituted heteroaromatic ring;

-Q - is-O-, -S - or a group-CXX'-,

X and X', which may be identical or different, represent a hydrogen atom, halogen atom, cyano, possibly substituted alkyl group, or a group-ORa, -SRaor-CORb; or one of X or X' is a hydroxyl group, and the other accepts the above specified values; or X and X' together form a group =O or =S;

Rarepresents a possibly substituted alkyl, aryl or acyl group;

Rbrepresents a possibly substituted alkyl or aryl group, or accept the value ORcor-NRcRd;

Rcand Rdthat may be the same or different, represent a hydrogen atom, possibly substituted alkyl or aryl group is y;

Y represents a nitrogen atom or a group CR9;

R1represents a possibly substituted alkyl, alkenylphenol, alkenylphenol, cycloalkyl, aryl group, heterocyclic, benzoheterocycles or amino group;

R2represents a hydrogen atom, possibly substituted alkyl or carboxylic acyl group; or a group-SO2R1;

R3and R4that may be the same or different, represent a hydrogen atom, halogen atom, possibly substituted alkyl, CNS, cycloalkyl or amino group or possibly substituted heterocyclic group; and

R9represents a hydrogen atom or a possibly substituted alkyl group;

provided that when Q takes the value of-O - or-S-, ring A represents a 5-membered substituted or unsubstituted heteroaromatic ring; and

provided that when the substituent R1represents a substituted alkyl, it is not a group of the formula:

where the Deputy X represents oxygen atom or sulfur, and each of the substituents R6, R7and R8represents a hydrogen atom or a possibly substituted alkyl group.

When A is A 5-membered heterocyclic ring, he predpochtitel is but puts a substituted or unsubstituted thiophene, furan, pyrrole, thiazole, isothiazol, pyrazol, imidazole, oxazole or isoxazole ring.

The ring A is any of the substituents at the carbon atom preferably represents a halogen atom, ceanography, group-COOR10(where the substituent R10represents a hydrogen atom or a possibly substituted alkyl group), or possibly substituted alkyl, CNS, aryloxy, heterocyclic or amino group. Preferably such substituting groups are fluorine atoms and chlorine.

Any of the substituents at the nitrogen atom of ring A preferably represents a substituted or unsubstituted alkyl, CNS, amino or aryl group, especially a methyl group.

Any of those present alkyl groups in the molecule preferably has from 1 to 8 carbon atoms, more preferably from 1 to 6 carbon atoms, especially from 1 to 4 carbon atoms. Specific preferred unsubstituted alkyl or alkalmazasa groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert.-butyl, methoxy, ethoxy and n-propoxy.

If any of the alkyl groups in the molecule is substituted, the substituents can be, for example, one or more halogen atoms (e.g. fluorine, chlorine or bromine), alkoxy - or alkylthio containing from 1 to 4 carbon atoms, (e.g. the, methoxy - or ethoxy-), hydroxy-, nitro-, mercapto-, amino, substituted amino, carbamoyl, substituted carbamoyl, thiocarbamoyl, substituted thiocarbamoyl, cyano, acyl, aryl or heteroaryl group. Particularly preferred substituted alkilsoderjasimi groups are chloromethylene, brometalia, dichlorethylene, triptoreline, deformedarse, cyanomethylene, methoxyaniline or amoxicilina.

Any of those present alkenyl or etkinlik groups in the molecule preferably has from 2 to 6 carbon atoms, for example vinyl, allyl or propargyl. Any such Alchemilla or Alchemilla group is preferably unsubstituted, although, if necessary, it can be substituted, e.g. by halogen.

Any of those present cycloalkyl groups in the molecule preferably has from 3 to 7 carbon atoms,especially preferred cyclopentolate or tsiklogeksilnogo group. They are preferably unsubstituted.

Any of the participants of aryl groups in the molecule preferably represents phenyl which is preferably substituted by one or more alkyl, alkoxy, alkoxycarbonyl or alkylthiophene containing from 1 to 4 carbon atoms (and which, in turn, may themselves be substituted), atoms ha is ogena, cyano-, aminosulfonyl or a nitro group; especially preferably, the phenyl group has been substituted by one or more chlorine atoms, bromine or fluorine, and/or one or more methyl, methoxy-, triptoreline, methylthio-, methoxycarbonylamino, ethoxycarbonylphenyl or nitro groups.

Any heterocyclyl groups in the molecule, which is not a ring And preferably represents a furyl, thienyl or nitrogen-containing heterocycle, for example 5 - or 6-membered heterocyclic ring, for example pyrrolyl, oxazolyl, isoxazolyl, isothiazolin, pyrimidinyl, triazolyl or imidazolyl. Deputy R1may also preferably be a pyridyl, furyl, thienyl or bicyclic heterocyclyl group, for example triazolamtriazolam, triazolopyrimidines or pyrazolopyrimidine.

Any benzoheterocycles groups in the molecule preferably is benzothiophenes, benzodioxole, quinoline, khinazolinov, benzothiazoline or dihydrobenzofuranyl group.

Any of the halogen atoms in the molecule preferably is a fluorine atom, chlorine or bromine.

Any of the substituted amino groups in the molecule may be mono - or disubstituted, for example, alkilani containing from 1 to 4 carbon atoms, alkenylamine containing from 2 to 4 carbon atoms, ka is baturinym or carboxylic acyl, alkoxycarbonyl, alkylcarboxylic or dialkylammonium groups in which the alkyl group contains from 1 to 4 carbon atoms.

Used herein, the term "acyl" refers to the residue of carboxylic, sulfonic or fosforsoderzhashchie acids, for example, group alkanoyl, alkanoyl, alkanoyl, cycloalkenyl, arkanoid, aroyl, carbarnoyl, thiocarbamoyl, alkoxycarbonyl, sulfonyl, sulfamoyl and phosphonyl, in which any alkyl, alkeline, alkyline or aryl groups can be substituted or unsubstituted.

Especially preferred group, in which R1may be a methyl, chloromethyl, methyl bromide, cyanomethyl, trifluoromethyl or 2,2,2-triptorelin.

Deputy R2preferably represents a hydrogen atom.

Each of R3and R4preferably represents a hydrogen atom, a methyl, a methoxy group or a chlorine atom.

Particularly preferably, if the substituents R3and R4identical and most preferably, when both of them represent a methoxy group.

Ring A is preferably a benzene (possibly substituted by fluorine atoms, chlorine, bromine, methyl, methoxy or ethoxypropane) or pyrazol (possibly substituted by one or more methyl groups).

Deputy Q preferably of t is made by a-CH 2-, -CH(CH3)-, -S - or-O-.

Preferred salts of the compounds of formula I are the salts formed by strong bases, such as alkali metal salts (e.g. potassium or sodium), salts of amines (for example, tryptamine, Diisopropylamine, cyclohexylamine or piperidine).

The most preferred compounds of the present invention are compounds, which are listed below in the Examples.

Another object of the present invention is a method for sulfonamida formula I, which consists in the interaction of the amine of the formula:

where the substituents A, Q, Y and R2-R4take the above values, with an appropriate sulfonic anhydride of formula (R1SO2)2O or sulphonylchloride formula R1SO2Hal, where Hal is a halogen atom, and the substituent R1takes the values described previously, with the formation of the desired connection.

The reaction is very easily proceeds in the presence of a base, for example an organic base, such as pyridine.

In turn, the compounds of formula II can be obtained by the reaction of a substituted amine of the formula:

where A, Q, and R2take the above meanings, in the presence of a base with the compound of the formula:

where the substituents Y, R3and R4take the above values, and Deputy L is a leaving group, with formation of the desired connection.

Leaving group L may be any suitable group, but preferably it represents a halogen atom, especially a chlorine atom, or methylsulfonyl group.

As grounds, it is preferable to use alkylate, for example tert.-utility, and the reaction is preferably carried out in an environment of solvent such as tetrahydrofuran.

The compounds of formula II, in which the substituent R2represents a hydrogen atom, an alternative can be obtained by reduction of the corresponding nitro compounds of the formula:

where the substituents A, Q, Y, R3and R4take the above values.

Recovery is convenient to carry out using tin chloride(II); an alternative method is to process the iron in an acidic environment, particularly preferably in triperoxonane acid and/or its anhydride by methods which are in themselves known. According to the latest technique originates in the transformation of the nitro group-NHCOCF3, which is then converted into the amino group by the action of a base, for example potassium carbonate.

If necessary, the compounds of formula II can the be converted into other compounds of formula II with known methods. For example, the compounds of formula II, in which the Deputy X or X' represents an alkyl group, can be obtained from corresponding compounds of formula II in which Q represents-CH2-, and R2is a hydrogen atom, initially protected amino group, for example, by reaction of the compound with di-tert.-BUTYLCARBAMATE, processing secure connections alkylating agent, such as methyliodide, in the presence of a strong base, followed by removal of the protection of the amino group, for example, triperoxonane acid.

In turn, the compounds of formula V can be obtained by the interaction of the compounds of the formula:

where the Deputy And accepts the above meanings, and Hal is a halogen atom, in the presence of a base with a compound corresponding to the formula IV, in which the substituents R3and R4take the above values, and Deputy L is a group-OH, where Deputy Q takes the values described previously.

Alternative compounds of formula V can be obtained by the reaction of nitro compounds of the formula:

where the substituents A and Q take the values described previously, as Deputy L represents a leaving group (preferably, a chlorine atom or imidazol-I-yl), in the presence of a base with the compound fo the mules R 3C(=NH)YHC(=NH)R4where the substituents Y, R3and R4take the above values.

The preferred base is diisopropylethylamine.

The compounds of formula II, where the Deputy And represents the N-methylpyrazole ring, and the substituent R3is a hydrogen atom, an alternative can be obtained by the reaction of dimethylaminoacetonitrile formula:

where the substituents Q, Y, R3and R4take the above values, with methylhydrazine in acetic acid with the formation of the target compounds.

The initial substance in the above-described processes, in particular especially compounds of formulas III, IV, VI, VII and VIII are either known compounds or can be obtained by known methods from related compounds, which are well known qualified in this area specialists.

Salts of compounds of formula I can be obtained by known methods by treatment of the corresponding free compounds with a suitable base in a suitable solvent (e.g. ether).

The compounds of formula I in which the substituent R2is different from a hydrogen atom, an alternative can be obtained from the salts of the compounds of formula I by reaction with a suitable alkylating or allermuir agent containing the desired group R2, methods, and similar is known.

The compounds of formula I have a weed-killing activity against a broad spectrum of broadleaf and grass weeds, but are relatively safe for some crops. Therefore, they can be used as selective serviceof, in particular, for the destruction of a large number of weeds in crops of cereals, sugar beet and other crops, for example wheat, barley, maize, soybean, oilseed rape, cotton or rice.

Thus, another object of the present invention is a method for killing weeds in areas littered with weeds or on sites which assume their appearance, which is handling the above mentioned areas effective amount of one or more compounds of formula I.

The desired doses of the compounds of the formula I or their salts are doses in the range of from 0.001 to 2 kg/ha, preferably from 0.005 to 1 kg/ha, more preferably from 0.01 to 0.5 kg/ha

Another object of the present invention are preparative forms, which contain one or more compounds of the present invention in a mixture with acceptable carrier and/or surface-active agent.

Preparative forms usually contain 0.01 to 99 wt.% compounds of the present invention and generally initially prepared in the form of the of oncentrates, containing from 0.5 to 99%, preferably from 0.5 to 85%, and more preferably from 10 to 50 wt.% these compounds. Such concentrates are diluted, if necessary, before processing stations so that the content of the active ingredient used in the formulation ranged from 0.01 to 5 wt.%.

As the carrier there may be used water, which in some cases may contain an organic solvent, although usually it is not used. Flowable suspension concentrate can be obtained by grinding the compound with water, wetting and suspenders agent, for example, xanthan resin.

As the carrier there may be used water-immiscible organic solvent, for example hydrocarbons, boiling in the range of 130-270°C, for example xylene, in which is dissolved or suspendered compound of the present invention. Can also be obtained emulgirujushchie concentrate containing not miscible with water, solvent and surfactant so that the concentrate acts as a self emulsifiable oil by mixing it with water.

As the carrier can be used, and the solid product which is subjected to fine grinding or pelleting. Examples of acceptable solid carriers are limestone, clay, sand, mica, chalk, attapulgite, diatom is t, perlite, thick, silicas, silicates, lignosulfonates and solid fertilizers. The media can be of natural or synthetic material, or a modified natural product.

Wettable powders, soluble or dispergirujutsja in water, can also be obtained by mixing the compounds of the present invention in the form of particles with a carrier in the form of particles or when spraying molten compound on a carrier in the form of particles, mixed with a wetting agent and dispersing agent, and then crushed the entire powder mixture.

Aerosol formulations can be prepared by mixing the compounds of the present invention with propellents, for example with polygalacturonase alkanes, such as dichloromethane, and, if necessary, with a solvent.

The term "surfactant" in the broad sense includes materials, called emulsifying agents, dispersing agents and wetting agents. Such agents are well known in this field.

Used surfactants can be anionic, such as mono - or diesters of phosphoric acid and ethoxylated fatty alcohols, or salts of such esters, sulfates of fatty alcohols, such as sodium dodecyl sulphate, ethoxylated sulfates of fatty IPN is tov, ethoxylated alkylphenol sulfates, lignosulfate, petroleum sulfonates, alkylarylsulfonates, such as alkylbenzenesulfonate or lower alkylnaphthalene, salts of sulfonated condensation products of naphthalene with formaldehyde, or a more complex sulfonates such as sulfonates amides, for example sulphonated condensation product of oleic acid and N-methyltaurine or diallylmalonate, for example the sodium salt of sulfated dioctylmaleate.

Surfactants can also be a non-ionic agents, for example condensation products or esters of fatty acids, fatty alcohols, fatty acid amides or alkyl substituted phenols with ethylene oxide, fatty acid esters from simple esters of polyhydric alcohols, for example sorbitane esters of fatty acids, condensation products of such esters with ethylene oxide, for example polyoxyethylenesorbitan esters of fatty acids, block copolymers of ethylene oxide and propylene oxide, acetylenic glycols such as 2,4,7,9-tetramethyl-5-Decin-4,7-diol, or ethoxylated acetylenic glycols.

Surfactants can be cationic agents, such as alkyl and/or aryl-substituted Quaternary ammonium compounds such as cetyltrimethylammonium bromide, and ethoxylated fatty tertiary amine is mi.

Preferred surfactants are ethoxylated sulfates of fatty alcohols, ligninsulfonate, alkylarylsulfonate, salts of sulfonated condensation products of naphthalene with formaldehyde, oleyl-N-methyltaurine sodium, diallylmalonate, ethoxylated ALKYLPHENOLS and fatty alkylalkoxysilane.

Active compounds of the present invention, especially those presented in the Examples below, can be mixed with other pesticides, for example with another herbicide, fungicide or insecticide or plant growth regulator. Especially preferably use a different herbicide. Acceptable additional herbicides are triacetin, linuron, MSRA, dichlorprop, isoxaben, diflufenican, metolachlor, fermeture, oxyfluorfen, fomesafen, bentazon, prometryn, norflurazon, glamazon, EPTC, imazaquin, more preferably Isoproturon, sentimentmeasures, trifluralin, ioxynil, bromoxynil, benazolin, mecoprop, fluroxypyr, alachlor, acifluorfen, lactofen, metribuzin, pendimethalin, and most preferably ethofumesate and phenmedipham.

Compounds of the present invention can be used for treatment of plants, soil, terrestrial and aquatic areas, and especially areas where growing crops or for which they'll have to grow Atisa. These compounds possess both pre-emergence and post-harvest activity.

The invention is illustrated by the following examples.

EXAMPLE

EXAMPLE A1

1,1,1-Cryptor-2'-(4,6-dimethoxypyrimidine-2-ylmethyl)methanesulfonanilide

(a) 2-(4,6-Dimethoxypyrimidine-2-ylmethyl)aniline

Method 1

To a solution of o-toluidine (5.35 g) in dry tetrahydrofuran (100 ml) under stirring at -70°C in nitrogen atmosphere is added dropwise n-utility (21 ml of a 2.5 M solution in hexane). The resulting suspension allowed to warm to 5°receiving light yellow solution. In reational the mixture was bubbled with dry carbon dioxide for approximately 6 minutes, the Solvent is evaporated with stirring under high vacuum at room temperature. The obtained white solid is suspended in dry tetrahydrofuran and cooled to 70°C in an atmosphere of nitrogen and added dropwise within 15 min add tert.-utility (70 ml of a 1.6 M solution in pentane). Mixture is allowed to warm to -15°C and stirred at this temperature for 75 minutes the Mixture is cooled to -70°C and added dropwise a solution of 4,6-dimethoxy-2-methylsulfonylamino (10.9 g) in tetrahydrofuran. The mixture was stirred at -75°C for 60 min and left overnight at room temperature. The solvent is evaporated in vacuo, to the residue at which osphere nitrogen cooling water with ice add 2 N. hydrochloric acid. Then add 250 ml of water, the obtained turbid solution is alkalinized with a saturated solution of sodium bicarbonate and extracted with ether (2×400 ml). The combined extracts are washed with saturated sodium bicarbonate solution, dried and evaporated. The obtained orange oil distilled chromatographytandem will receive 2 g of the product in a solid yellow color, TPL 82-84°C.

Method 2

(I) of 4,6-Dimethoxy-2-(2-nitrobenzyl)pyrimidine

To a suspension of dichlorhydrate of maleimide (73.2 g) in methylene chloride (400 ml) at -40°C in nitrogen atmosphere with stirring, add dropwise diisopropylethylamine (240 ml), stirred for 25 min, get the suspension a To suspension carbonyldiimidazole (53.3 g) in methylene chloride (400 ml) with stirring at room temperature portions add 2-nitrophenyloctyl acid (65.16 g). The resulting solution was stirred for 10 min and for 30 min at -40°C under stirring is added dropwise to a suspension A. the Mixture is stirred at -40°C for 45 min and at room temperature over night. The solution was washed with water (400 ml), 2 N. HCl (400 ml) and saturated sodium bicarbonate solution (400 ml), dried and evaporated. The obtained solid orange color mixed with 2-propanol (60 ml) for 10 min and filtered. The filtrate is washed with 50 ml of 2-propanol and sushi is t, obtain 32.6 g of the desired product as a yellow solid, TPL 92-93°C.

(II) 2-(4,6-Dimethoxypyrimidine-2-ylmethyl)aniline

To a suspension of chloride dihydrate tin(II) (133 g) in ethanol (300 ml) with stirring, add the product from step (I). The mixture is boiled for 2 h, poured into ice water (2500 ml) and extracted with ethyl acetate (3×500 ml). The combined extracts are washed with saturated sodium chloride solution, dried and evaporated, to obtain 24.3 g of the desired product as a brown solid, TPL 82-84°C.

(b) 1,1,1-Cryptor-2'-(4,6-dimethoxypyrimidine-2-ylmethyl)-methanesulfonanilide

To a solution of 2-(4,6-dimethoxypyrimidine-2-ylmethyl)aniline (0.98 g) and pyridine (0.31 g) in dry methylene chloride (15 ml) at -70°C in nitrogen atmosphere are added in several portions triftormetilfullerenov anhydride (1.12 g). Received the orange solution stirred for 2 h at -75°C and allowed to warm to room temperature over 1 h the Mixture was washed with water, dried, get a red oil, which is distilled chromatographytandem and recrystallization from petroleum ether 60-80°receive 0.4 g of the product as a white solid, TPL 99-100°C.

EXAMPLE A2

1,1,1-Cryptor-2'-[1-(4,6-dimethoxypyrimidine-2-yl)ethyl]methanesulfonanilide

(a) tert.-Butyl-[2-(4,6-dimethoxypyrimidine-2-ylmethyl)phenyl]carbamate

A solution of the product article is Hai (a) of Example A1 (24.1 g) and di-tert.-BUTYLCARBAMATE (24 g) is boiled in dry tetrahydrofuran (250 ml) under nitrogen atmosphere for 4 hours The solvent is evaporated, the obtained brown oil is crystallized from hexane (200 ml), obtain 28 g of the desired compound as a brown solid, TPL 98-100°C.

(b) tert.-Butyl-[2-[1-(4,6-dimethoxypyrimidine-2-yl)ethyl]-phenyl]carbamate

The product of the above stage (a) (1 g) dissolved in dry tetrahydrofuran (20 ml) and under nitrogen atmosphere add tetramethylethylenediamine (1.1 ml). The solution is cooled to -70°C and added dropwise 1.7 M solution of tert.-utility in pentane (4.3 ml). The mixture is then stirred at -20°C for 1 h, cooled to -70°C and add methyliodide (0.45 g). The reaction mixture is allowed to warm to 0°and add a saturated solution of ammonium chloride (25 ml). The mixture is extracted with tetrahydrofuran (3×50 ml), the combined extracts dried and evaporated, and the obtained pale-brown solid is triturated with hexane, to obtain 0.73 g of the desired product, TPL 119-121°C.

(a) 2-[1-(4,6-Dimethoxypyrimidine-2-yl)ethyl]aniline

The product of the above stage (b) (5.0 g) is added to triperoxonane acid (25 ml) and the resulting solution was stirred at room temperature for 3 hours the Solution is evaporated, the residue triturated with diisopropyl ether and cooled with a mixture of dry ice-acetone. The solid is filtered off, washed with diisopropyl ether, to obtain 3.5 g of the desired product,TPL 136-139°C.

(d) 1,1,1-Cryptor-2'-[1-(4,6-dimethoxypyrimidine-2-yl)ethyl]-methanesulfonanilide

A named connection receive according to the method similar to that described in stage (b) of Example A1, using as initial product of the above stage (C), TPL 132-133°C.

EXAMPLE A3

1,1,1-Cryptor-2'-(4,6-dimethoxy-1,3,5-triazine-2-ylmethyl)methanesulfonanilide

(a) 2,4-Dimethoxy-6-(2-nitrobenzyl)-1,3,5-triazine

To a suspension of 2-nitrophenylacetic acid (3.4 g) in methylene chloride (30 ml) under stirring portions add carbonyldiimidazole (3.34 g) and stirred the mixture at room temperature for 30 minutes the resulting red solution under stirring is added dropwise to a suspension of zinc salts of dimethylimidodicarbonimidic (3.0 g) in methylene chloride (25 ml) at -35°C. the Reaction mixture was stirred at room temperature overnight and poured into water (100 ml). The mixture is extracted with methylene chloride (3×50 ml), the combined extracts dried and evaporated. The resulting oil red triturated with ether, to obtain 1.41 g of the desired product as a solid pale brown, TPL 91.6-92.3°C.

(b) 1,1,1-Cryptor-2'-(4,6-dimethoxy-1,3,5-triazine-2-yl-methyl)methanesulfonanilide

A named connection receive by methods similar to those described in Example A1(a), Method 2(II) and A1(b), using as recognize the aqueous product of the above stage (A), TPL 101-108°C.

EXAMPLE A4

N-[3-(4,6-dimethoxypyrimidine-2-ylmethyl)-2-pyridyl]-1,1,1-triftormetilfullerenov

(a) tert.-Butyl-(3-methyl-2-pyridyl)carbamate

A solution of 2-amino-3-methylpyridine (20 g) and di-tert.-BUTYLCARBAMATE (46.8 ml) in dry tetrahydrofuran boiled for 3 h and evaporated. The obtained dark brown oil is dissolved in ethyl acetate (400 ml), washed with 1 N. citric acid (3×200 ml) and a saturated solution of sodium chloride, dried and evaporated. The obtained pale-yellow solid residue is crystallized from a mixture of hexane-diisopropyl ether (1:2), obtain 6.5 g of the desired product as a pale-yellow solid, TPL 135-137°C.

(b) tert.-Butyl-[3-(4,6-dimethoxypyrimidine-2-ylmethyl)-2-pyridyl]-carbamate

The product of the above stage (a) (5 g) dissolved in dry tetrahydrofuran (100 ml) and under nitrogen atmosphere at -70°C is added dropwise tert.-utility (19.2 ml of 2.5 M solution in heptane). The mixture is stirred at -70°C for 20 min, then at 5°C for 3 hours the Mixture is cooled to -70°add 4,6-dimethoxy-2-methylsulfonylamino (5.42 g) and stirred at -70°C for 1 h and at room temperature over night. To the mixture is added a saturated solution of ammonium chloride (500 ml) and extracted with ethyl acetate (2×100 ml). The combined extracts washed with a saturated solution of chloride on the rija (50 ml), dried and evaporated. The obtained orange oil is triturated with hexane, to obtain 5.35 g of the desired product as a solid pale yellow color, TPL 89-92°C.

(C) N-[3-(4,6-dimethoxypyrimidine-2-ylmethyl)-2-pyridyl]-1,1,1-triftormetilfullerenov

A named connection receive according to the method similar to that described in stage (b) of Example A1, using as initial product of the above stage (b), so pl. 124-126°C.

EXAMPLES A5-A17

Methods similar to those described above in Example A1, can be obtained the following compounds of formula Ia, where a is a =CR5; Deputy Q represents-CH2-; Deputy R2represents N; b, D and E take the value of the =CH-; and each of the substituents R3and R4represents a methoxy group:

ExampleYR5R1TPL (°)
A5CHNCH2CN116-117
A6CHClCH2CN162-163
A7CHClCF3113-115
A8CHFCH2CN162-163
A9CHFCF3100-102
A10CHMeCH2CN
A11CHMeCF3
A12NFCH2CNorange oil
A13NFCF3
A14NMeCH2CN
A15NMeCF3
A16NClCH2CN31
A17NClCF3orange oil

EXAMPLES A18-A20

Methods similar to those described above in Example A1, can be obtained the following compounds of formula Ia, where a is a nitrogen atom; Deputy Q represents-CH2-; Deputy R2represents N; b, D and E take the value of the =CH-; and each of the substituents R3and R4represents a methoxy group:

ExampleYR1
A18CHCH2CN
A19NCH2CN
A20NCF3

EXAMPLES A21-A68

Methods described above can be obtained the following compounds of formula 1A where the substituent R2represents a hydrogen atom; each of the substituents R3and R4represents a methoxy group, and Deputy represents-CH:

td align="center"> SNtd align="center"> SN
ExYR1AndInDE
A21SNCF3NNSNSN
A22SNCF3NSNNSN
A23SNCF3NSNSNN
A24SNCF3SNNNSN
A25SNCF3SNNSNN
A26SNCF3SNNN
A27SNCF3CClNNSN
A28SNCF3CClNSNN
A29SNCF3CClSNNN
A30SNCF3CFNNSN
A31SNCF3CFNSNN
A32SNCF3CFSNNN
A33SNCH2CNNNSNSN
A34SNCH2CNNSNNSN
A35SNCH2CNNSNSNN
A36SNCH2CNSNNNSN
A37CH2CNSNNSNN
A38SNCH2CNSNSNNN
A39SNCH2CNCClNNSN
A40SNCH2CNCClNSNN
A41SNCH2CNCClSNNN
ASNCH2CNCFNNSN
A43SNCH2CNCFNSNN
A44SNCH2CNCFSNNN
A45NCF3NNSNSN
A46NCF3NSNNSN
ANCF3NSN SNN
A48 motorwayNCF3SNNNSN
ANCF3SNNSNN
A50NCF3SNSNNN

CH
continuation
A51NCF3CClNNCH
A52NCF3CClNCHN
A53NCF3CClCHNN
A54NCF3CFNNCH
A55NCF3CFNCHN
A56NCF3CFCHNN
A57NCH2CNNNCH
A58NCH2CNNCHNCH
A59NCH2CNNCHCHN
A60NCH2CNCHNNCH
A61NCH2CNCHNCHN
A62NCH2CNCHCHNN
A63NCH2CNCClNNCH
A64NCH2CNCClNCHN
A65NCH2CNCClCHNN
A66NCH2SNCFNNCH
A67NCH2CNCFNCHN
A68NCH2CNCFCH NN

EXAMPLES A-A

Methods described above can be obtained the following compounds of formula Ia, where the substituent R2represents H; each of the substituents R3and R4represents a methoxy group; And represents a =CR5; and Deputy Q represents-CH2is:

ExYR1R5BDEM Pt (°C)
ASNCF3NNSNSN
A70SNCF3NSNNSN
A71SNCF3NSNSNN
A72SNCF3ClNSNSN
A73 motorwaySNCF3ClSNNSN
A74SNCF3ClSNSNN
A75The n CF3FNSNSN
A76SNCF3FSNNSN
ASNCF3FSNSNN
ASNCH2CNNNSNSN
ASNCH2CNNSNNSN
A80SNCH2CNNSNSNN

td align="center"> N A94
continuation
A81SNCH2CNClNCHCH
A82SNCH2CNClCHNCH
ASNCH2CNClCHCHN
ASNCH2CNFCHCH
A85SNCH2CNFCHNCH
A86SNCH2CNFCHCHN
87 motorwayNCF3HNCHCH
A88NCF3HCHNCH
ANCF3HCHCHN
ANCF3ClNCHCH
ANCF3ClCHNCH
92NCF3ClCHCHN
A93NCF3FNCHCH
NCF3FCHNCH
A95NCF3FCHCHN
A96 motorwayNCH2CNHNCHCH
ANCH2CNHCHNCH
ANCH2CNHCHCHN
A99 motorwayNCH2CNClNCHCH
A100NCH2CNClCHNCH
A101NCH2CNClCHCHN
A102NCH2CNFNCHCH
A103NCH2CNF/td> CHNCH
ANCH2CNFCHCHN
ASNCH2CNHCHCClCH175-176
ASNCH2CNHCHCFCH110-111
A107SNCF3HCHCFCH112-114
A108SNCF3HCHCBrCH87-88
ASNCH2CNFCHCFCH185-186
ANCH2CNHCHCHCH186-188
A111 motorwaySNCF3FCHCFCH106-107
A112SNCH2ClFCHCF 140-141
A113SNMeFCHCFCH173-174
ASNCH2CNClCHCClCH211-214
ASNCH2CNFCHCMeCH178-181

continuation
ASNCH2ClClCHCHCH142-143
ANCH2CNClCHCClCHyellow oil
ASNCH2CNFCHC(OMe)CH161-163
ASNCH2CNOMeCHCFCH189-190
A120SNCH2CNFCHC(OEt)CH115-116
ANCH2Cl FCHCHCH141-142
ASNCH2ClFCHCHCH138-139
ASNCH2BrFCHCHCH137-138
ASNCH2CF3FCHCHCH141-142
ASNCH2CF3ClCHCHCH153-154

EXAMPLES A-A

Methods described above can be obtained the following compounds of formula Ia, where the substituent R2represents H; each of the substituents R3and R4represents a methoxy group; And represents a =CR5; and Deputy Q represents-CHMe-:

ExampleYR1R5BDETPL (°)
ACHCH2CNHCHCHCH133-135
ACHCH2CNClSNCHCH133-135

EXAMPLE B

EXAMPLE B1

N-[3-(4,6-Dimethoxypyrimidine-2-ylthio)-1,5-dimethyl-1H-pyrazole-4-yl]-1,1,1-triftormetilfullerenov and N-[5-(4,6-dimethoxypyrimidine-2-ylthio)-1,3-dimethyl-1H-pyrazole-4-yl]-1,1,1-triftormetilfullerenov

(a) 5-(4,6-dimethoxypyrimidine-2-ylthio)-3-methyl-4-nitro-1H-pyrazole

To a solution of 4,6-dimethoxy-2-mercaptopyrimidine (4.65 g) in an aqueous solution of potassium hydroxide (1.7 g in 75 ml of water) is added dropwise a solution of 1,4-dinitro-3-methylpyrazole (4.65 g), dissolved in minimum quantity of ethanol. The reaction proceeds ectothermic and upon its completion the mixture is stirred for 45 minutes the precipitation is filtered off, washed with fresh water, dried, obtain 6.3 g of the desired product, TPL 175-176°C.

(b) 5-(4,6-Dimethoxypyrimidine-2-ylthio)-1,3-dimethyl-4-nitro-1H-pyrazole and 3-(4,6-dimethoxypyrimidine-2-ylthio)-1,5-dimethyl-4-nitro-1H-pyrazole

To a mixture of 60%suspension of sodium hydride (0.47 g) and dry dimethylformamide (20 ml) under stirring and cooling in an ice bath portions add the product of the above stage (a) (3.15 g). At the end of the addition the mixture is stirred for 10 min at room temperature and added dropwise to methyliodide (1.7 g)SMEs stirred at room temperature for 2.5 h, pour ice water (50 ml), extracted with ethyl acetate (3×50 ml), the combined extracts washed with water and dried with magnesium sulfate. Filtration and subsequent evaporation produce the crude product as oil.

The crude product is subjected to rapid chromatography on silica gel (eluent ethyl acetate-petroleum ether 40-60°, 1:1) and produce two new products. The evaporation of the fractions containing the pure substance, there are two different solid product.

According to the results of thin-layer chromatography (TLC) on silikagelevye plates (eluent ethyl acetate-petroleum ether 40-60°, 1:1) one product has an Rfabout 0.75 (apparently, 5-(4,6-dimethoxypyrimidine-2-ylthio)-1,3-dimethyl-4-nitro-1H-pyrazole), and the other Rfabout 0.3 (apparently 3-(4,6-dimethoxypyrimidine-2-ylthio)-1,5-dimethyl-4-nitro-1H-pyrazole). The product yield with Rf0.75 to 1.3 g TPL 124-125°C. the product Yield with Rf0,3 is 0.82 g, TPL 155-156°C.

(b) 3-(4,6-Dimethoxypyrimidine-2-ylthio)-1,5-dimethyl-1H-pyrazole-4-amine and 5-(4,6-dimethoxypyrimidine-2-ylthio)-1,3-dimethyl-1H-pyrazole-4-amine

A mixture of the product from step (b) (Rf0,3) (2.4 g) and chloride dihydrate tin(II) (8.7 g) in ethanol (100 ml) is stirred at boiling for 4 hours, the Ethanol is evaporated in vacuo, the residue is stirred with water (100 ml) and alkalinized with solid sodium bicarbonate. Add ethyl acetate (100 ml), the scientists emulsion is filtered through a kieselguhr pad and the organic layer separated. The precipitate is washed with ethyl acetate (total 75 ml)and the aqueous layer was extracted with ethyl acetate (2×50 ml). The combined organic layers washed with water (50 ml), separated and dried with magnesium sulfate. After evaporation of the ethyl acetate is oil, which crystallizes. The crude product is purified by rapid chromatography on silica gel (eluent ethyl acetate), allocate a new product with Rf0.3 (TLC on silica gel, eluent ethyl acetate). The evaporation of the fractions containing pure new product, obtain 1.33 g of solid substance with TPL 104-105°C.

A similar method get another isomer, yield 2.6 g, TPL 74-75°C.

(g) N-[3-(4,6-Dimethoxypyridine-2-ylthio)-1,5-dimethyl-1H-pyrazole-4-yl]-1,1,1-triftormetilfullerenov (BA) and N-[5-(4,6-dimethoxypyrimidine-2-ylthio)-1,3-dimethyl-1H-pyrazole-4-yl]1,1,1-triftormetilfullerenov (BB)

To a solution of aminopyrazole with the above stage (in) (Rf0.3, 1.2 g) in dry methylene chloride (30 ml) under stirring and at -60°With (cooling bath of dry ice-acetone) is added dropwise a solution of triftormetilfullerenov anhydride (1.2 g) in dry methylene chloride (10 ml). At the end of the addition the temperature of the mixture is slowly brought to room temperature and stirred over night. The obtained dark red solution was diluted with 100 ml of fresh methylene chloride, washed with water (25 ml), 1 M HCl (25 ml) and water (25 ml). The layers are separated, the organization of the mini layer is dried with magnesium sulfate, filtered, evaporated, receive semi-solid dark red substance. Rapid chromatography on silica gel (eluent ethyl acetate-petroleum ether 40-60°, 1:1) allocate a new product with Rf0.5 (TLC on silikagelevye plates, eluent ethyl acetate-petroleum ether 40-60°, 1:1). The fractions containing pure new product, evaporated, get the desired product (BA) as a white solid. Yield 0.83 g, TPL 203-204°C.

A similar method get another isomer (BB), yield 1.8 g, TPL 145-146°C.

EXAMPLE B2

1-Cyano-N-[3-(4,6-dimethoxypyrimidine-2-ylthio)-1,5-dimethyl-1H-pyrazole-4-yl]-1,1,1-triftormetilfullerenov (BA) and 1-cyano-N-[5-(4,6-dimethoxypyrimidine-2-ylthio)-1,3-dimethyl-1H-pyrazole-4-yl]-1,1,1-triftormetilfullerenov (B2B)

Aminopyrazole from stage (C) of Example B1 (Rfof 0.3, 0.8 g) dissolved in dry methylene chloride (10 ml) and with stirring, add the dry pyridine (0.23 g). The mixture is cooled to -78°C (bath of dry ice-acetone) and portions add cyanomethylphosphonate (0.4 g, 0,00285 mol). Mixture is allowed to slowly warm to room temperature and stirred for 2 days. The mixture is then diluted with ethyl acetate to 100 ml and washed with water, 1 M HCl, again with water and separate the layers. The organic layer was filtered, dried with magnesium sulfate, filtered and evaporated. The residue is subjected to rapid chromatography on silica gel (eluent, dieti the new ether), get a new product with Rf0,4 (approx) (TLC on silica gel, eluent diethyl ether).

Fractions with pure product are combined evaporated receive the desired product (BA) in the form of a solid yellow (700 mg), TPL 166-167°C.

A similar method get another isomer (B2B) in the form of solids, the output of 1.6,

EXAMPLE B3

1-Cyano-N-[4-(4,6-dimethoxypyrimidine-2-ylthio)-1-methyl-1H-pyrazole-5-yl]methanesulfonamide (BA) and 1-cyano-N-[4-(4,6-dimethoxypyrimidine-2-ylthio)-1-methyl-1H-pyrazole-3-yl]methanesulfonamide (BB)

(a) 2-(4,6-Dimethoxypyrimidine-2-ylthio)-3-(dimethylamino)-Acrylonitrile

A mixture of dimethylacetal of dimethylformamide (5.8 g) and 2-(4,6-dimethoxypyrimidine-2-ylthio)acetonitrile (5.1 g) was stirred at 100°C in oil bath for 5 h and left overnight at room temperature. The crude solid product is triturated with diisopropyl ether, to obtain the desired product in the form of a solid yellow color with the release of 5.4,

(b) 4-(4,6-Dimethoxypyrimidine-2-ylthio)-1-methylpyrazole-3-amine and 4-(4,6-dimethoxypyrimidine-2-ylthio)-1-methylpyrazole-5-amine

To a mixture of the product of the above stage (a) (2.6 g) and glacial acetic acid (10 ml) is added dropwise methylhydrazine (1.0 g), heated at an oil bath to 100°C and incubated for 3 hours. The mixture is allowed to cool and poured into water (100 ml). Then, the mixture neutrality is tons of solid sodium bicarbonate and extracted with ethyl acetate (3× 75 ml). The combined organic layers washed with water (30 ml), separated, dried with magnesium sulfate, filtered and evaporated. The oil obtained is subjected to rapid chromatography on silica gel (eluent pure ethyl acetate), receive mainly one product (Rf0.3, TLC on silica gel, eluent ethyl acetate). Fractions with pure product are combined evaporated, get no white product with the release of 2.2, Range1H NMR indicates that it is a 50/50 mixture of the two possible isomeric products. The obtained isomers were separated by preparative liquid chromatography high pressure. The process of evaporation of fractions containing clean isomers, get both products in the form of colorless crystals.

One of the products obtained (A) isolated with yields 480 mg, TPL 110-111°C (apparently, 4-(4,6-dimethoxypyrimidine-2-ylthio)-1-methylpyrazole-5-amine). Another product (B) (seems 4-(4,6-dimethoxypyrimidine-2-ylthio)-1-methylpyrazole-3-amine)selected with the release 800 mg, TPL 160-161°C.

(C) 1-Cyano-N-[4-(4,6-dimethoxypyrimidine-2-ylthio)-1-methyl-1H-pyrazole-5-yl]methanesulfonamide and 1-cyano-N-[4-(4,6-dimethoxypyrimidine-2-ylthio)-1-methyl-1H-pyrazole-3-yl] methanesulfonamide

A solution of pyrazole (a) above the stage (b) (475 mg) in methylene chloride (10 ml) cooled to -78°C (bath of dry ice-acetone) and with stirring, add PI is one (0.15 ml). Using a syringe is added dropwise a solution of cyanomethaemoglobin (250 ml) in methylene chloride (1 ml), then slowly heated to room temperature and stirred over night. The mixture is diluted with ethyl acetate and 100 ml, washed with water (30 ml), diluted hydrochloric acid (2×30 ml) and a saturated solution of sodium chloride (30 ml). The organic layer is separated, dried with magnesium sulfate, filtered, evaporated, receive off-white solid product (apparently, 1-cyano-N-[4-(4,6-dimethoxypyrimidine-2-ylthio)-1-methyl-1H-pyrazole-5-yl]methanesulfonamide) (BA). After recrystallization from ethanol allocate 350 mg of product, TPL 206-207°C. the Other isomer (BB) receive similar method, using as the source pyrazole (B) above the stage (b), the output of 650 mg, TPL 147-148°C.

EXAMPLE B4

N-[3-(4,6-Dimethoxy-1,3,5-triazine-2-yl)-1,5-dimethyl-1H-pyrazole-4-yl]-1,1,1-triftormetilfullerenov

(a) Diethyl-(5-methyl-4-nitropyrazole-3-yl)malonate

To a mixture of 60%suspension of sodium hydride (2.3 g) in dry tetrahydrofuran (100 ml) under stirring and cooling in an ice bath is added dropwise diethylmalonate (9.4 g), stirred for 10 min, after which small portions over 10 min add 1,5-dinitro-3-methylpyrazole (5.0 g), maintaining the temperature of 10-12°C. the Mixture is stirred at room temperature for 30 min and in those which begins approximately 5 min is added dropwise glacial acetic acid (3 ml). The mixture is diluted with ethyl acetate (400 ml), washed with water (2×30 ml), the organic layer is separated, dried with magnesium sulfate, filtered and evaporated. The residue is an oil which crystallizes when grinding with perroleum ether 60-80°C. Obtain 7.5 g of the desired product as a pale-yellow solid, TPL 100-102°C.

(b) (5-Methyl-4-nitropyrazole-3-yl)acetic acid

A mixture of potassium hydroxide (5.9 g), the product of the previous stage (7.5 g) and 50%aqueous ethanol (100 ml) is boiled under stirring for 1.5 hours, allowed to cool, evaporated almost to dryness, diluted with water (100 ml) and acidified with concentrated hydrochloric acid. The resulting mixture is heated to about 80°C for 0.5 hours, cooled and evaporated to dryness. The residue is treated with ethyl acetate (100 ml), washed with water (2×20 ml), the organic layer is separated, dried with magnesium sulfate, filtered and evaporated. Obtain 3.85 g of the desired product as a solid yellow color.

(C) Methyl-(5-methyl-4-nitropyrazole-3-yl)acetate

The product from the previous stage (3.85 g) was dissolved in methanol (75 ml)containing few drops of concentrated sulfuric acid. The resulting mixture is boiled under stirring for 2 h and allowed to cool. The methanol is evaporated in vacuo, the residue is dissolved in ethyl acetate, washed with water, organicheskikh separated, dried magnesium sulfate, filtered and evaporated. Obtain 4.0 g of the desired product as a cream solid color, TPL 132-133°C.

(d) Methyl (1,5-dimethyl-4-nitro-1H-pyrazole-3-yl)acetate and methyl (1,3-dimethyl-4-nitro-1H-pyrazole-5-yl)acetate

To a mixture of potassium carbonate (2.5 g) and dimethylformamide (30 ml) was added with stirring the product from the previous stage (3.3 g)in one portion add methyliodide (2.6 g), there is moderately exothermic reaction. The mixture is stirred over night at room temperature, diluted with 100 ml of water and extracted with diethyl ether (4×50 ml). The combined extracts washed with water (30 ml), separated, dried with magnesium sulfate, filtered and evaporated. Obtain 3.2 g of the desired isomeric mixture of products in the form of an oily solid.

(d) (1,5-Dimethyl-4-nitro-1H-pyrazole-3-yl)acetic acid and (1,3-dimethyl-4-nitro-1H-pyrazole-5-yl)acetic acid

To a solution of the product from the previous stage (3.2 g) in ethanol (25 ml) was added with stirring a solution of potassium hydroxide (1.7 g) in water (25 ml) and boiled under stirring for 3 hours the Mixture was evaporated almost to dryness, diluted with 50 ml of water, acidified with concentrated hydrochloric acid and evaporated. The residue is dissolved in ethyl acetate, washed with water, dried with magnesium sulfate, filtered and evaporated. Obtain 3.2 g of the desired isomeric mixtures and products in the form of a solid orange color.

(e) 2-(1,3-Dimethyl-4-nitro-1H-pyrazole-5-ylmethyl)-4,6-dimethoxy-1,3,5-triazine and 2-(1,5-dimethyl-4-nitro-1H-pyrazole-3-ylmethyl)-4,6-dimethoxy-1,3,5-triazine

The product from the previous stage (2.56 g) was dissolved in methylene chloride (50 ml) under nitrogen atmosphere, which is maintained for all subsequent operations. To the mixture add carbonyldiimidazole (2.0 g) and stirred for 30 minutes the resulting mixture with stirring is added dropwise to a suspension of zinc salts of dimethylimidodicarbonimidic (2.1 g) in methylene chloride (25 ml) at -35°C. the Reaction mixture is allowed to warm to room temperature and stirred over night. To the mixture is added water (50 ml) and methylene chloride (50 ml), filtered through diatomaceous earth, the layers separated, the aqueous layer was extracted with methylene chloride (3×30 ml). The combined organic layers washed with water, dried with magnesium sulfate, evaporated, obtain 3.8 g of crude product. Rapid chromatography on silica gel (eluent ethyl acetate) get two new products with Rf0.6 and about 0.4. The fractions containing products, evaporated and get:

Rf0.6: 1.0 g of 2-(1,3-dimethyl-4-nitro-1H-pyrazole-5-ylmethyl)-4,6-dimethoxy-1,3,5-triazine in the form of a crystalline solid and

Rf0.4: 1.0 g of 2-(1,5-dimethyl-4-nitro-1H-pyrazole-3-ylmethyl)-4,6-dimethoxy-1,3,5-triazine, TPL 145°C.

(W) 2-(4-Amino-1,5-dimethyl-4-nitro-1H-pyrazole-3-and is methyl)-4,6-dimethoxy-1,3,5-triazine

To a suspension of 10%palladium on coal (approximately 10 mg) in water (5 ml) add a solution of sodium borohydride (0.13 ml) in water (5 ml). Through a mixture miss nitrogen for 5 min added dropwise a solution of the product from the previous stage with Rf0.4 (0.5 g) in methanol (30 ml). The mixture was kept at room temperature for 30 min, then add acetic acid (1 ml). The mixture is filtered through kieselguhr, washed with methanol and evaporated almost to dryness. The residue was diluted with 15 ml of water, neutralized with solid sodium bicarbonate, extracted with ethyl acetate (3×30 ml), dried with magnesium sulfate, filtered and evaporated. Receive 400 mg of the desired product as a viscous orange oil.

(C) N-[3-(4,6-Dimethoxy-1,3,5-triazine-2-yl)-1,5-dimethyl-1H-pyrazole-4-yl]-1,1,1-triftormetilfullerenov

To a solution of the product from the previous stage (0.4 g) and pyridine (0.13 ml) in methylene chloride (15 ml) under stirring at -60°slowly added dropwise a solution of triftormetilfullerenov anhydride (0.43 g) in methylene chloride (5 ml). Mixture is allowed to slowly warm to room temperature and stirred for further 24 h the mixture is Then washed with water (10 ml), separated, dried with magnesium sulfate, filtered and evaporated. Receive 100 mg of the desired product as pale yellow viscous oil.

EXAMPLE B5

1-Cyano-N-[5-(4,6-dimethoxypyrimidine-2-ylthio)-1,2-dimethyl-1H-imida the ol-4-yl]methylsulfonyl

(a) 1,2-Dimethyl-4-bromo-5-nitro-1H-imidazole and 1,2-dimethyl-5-bromo-4-nitro-1H-imidazol

2-Methyl-4-bromo-5-nitroimidazol (35 g) is dissolved in an aqueous solution of sodium hydroxide (7 g). At room temperature is added dropwise dimethylsulfate (21.3 g) and the reaction mixture is stirred for 2 hours the precipitation is filtered off, washed with water, dried, obtain 33 g of a mixture of isomers, which are separated by chromatographytandem (eluent petroleum ether 60-80° - ethyl acetate, 8:2). Allocate 9.4 g of 1,2-dimethyl-4-bromo-5-nitro-1H-imidazole, TPL 98-99°C and 19.3 g of 1,2-dimethyl-5-bromo-4-nitro-1H-imidazole, TPL 160-162°C.

(b) 5-(4,6-Dimethoxypyrimidine-2-ylthio)-1,2-dimethyl-4-nitro-1H-imidazol

To a solution of 4,6-dimethoxy-2-mercaptopyrimidine (3.0 g) in aqueous sodium hydroxide solution (0.7 g per 100 ml water) is added dropwise a solution of 1,2-dimethyl-5-bromo-4-nitro-1H-imidazole (3.9 g) in ethanol (50 ml) and the mixture is stirred at room temperature for 6 hours the residue is filtered off, washed with water, dried and recrystallized from acetonitrile. Obtain 3.1 g of the desired product, TPL 228-230°C.

(b) 2,2,2-Cryptor-N-[5-(4,6-dimethoxypyrimidine-2-ylthio)-1,2-dimethyl-1H-imidazol-4-yl]ndimethylacetamide

A mixture of the product from the previous stage (7.0 g), triperoxonane acid (130 ml), triperoxonane anhydride (18 ml) and iron powder (5.0 g) is heated with stirring to 70� C and kept at this temperature for 8 hours the Mixture is filtered, the filtrate is poured on ice water, alkalinized 5 N. the sodium hydroxide solution and extracted with ethyl acetate. The combined extracts are dried with magnesium sulfate, the solvent evaporated, the residue is distilled chromatographytandem (eluent petroleum ether 60-80° - ethyl acetate, 8:2), obtain 5.0 g of the desired product, TPL 160-162°C.

(g) 5-(4,6-dimethoxypyrimidine-2-ylthio)-1,2-dimethyl-1H-imidazol-4-amine

To a solution of the product from the previous stage (5.4 g) in methanol (200 ml) is added potassium carbonate (1.5 g) and the reaction mixture is boiled for 6 hours the Mixture is filtered, the filtrate evaporated, the residue is recrystallized from acetonitrile, to obtain 2.6 g of the desired product.

(d) 1-Cyano-N-[5-(4,6-dimethoxypyrimidine-2-ylthio)-1,2-dimethyl-1H-imidazol-4-yl]methanesulfonamide

To a solution of the product from the previous step (1.0 g) in methylene chloride (10 ml) is added pyridine (0.3 g), cooled to -45°C and to one portion add cyanomethylphosphonate (0.5 g). The mixture was stirred at -45°C for 30 min, allowed to warm to room temperature and stirred over night at room temperature. The mixture is then poured into water, extracted with ethyl acetate and purified by chromatographytandem (eluent petroleum ether 60-80° - ethyl acetate, 8:2), obtain 0.7 g of the desired product, TPL 223-225° C.

EXAMPLE B6

1-Cyano-N-[2-(4,6-dimethoxypyrimidine-2-ylthio)-3-thienyl]-methanesulfonamide

(a) 4,6-Dimethoxy-2-(3-nitro-2-tianity)pyrimidine

To a solution of sodium hydroxide (1.2 g) in water (50 ml) was added 4,6-dimethoxy-2-mercaptopyrimidine (5.3 g) and the mixture is stirred at room temperature for 15 minutes To the mixture add a solution of 2-chloro-3-nitrothiophene (5.0 g) in ethanol (50 ml), stirred at room temperature for 6 hours, the precipitation is filtered off, washed with water, dried, obtain 7.6 g of the desired product, TPL 199-201°C.

(b) N-[2-(4,6-Dimethoxypyrimidine-2-ylthio)-3-thienyl]-2,2,2-triptorelin

A mixture of the product from the previous step (2.0 g), triperoxonane acid (50 ml), triperoxonane anhydride (5.0 ml) and iron powder (1.8 g) is heated with stirring to 70°C and kept at this temperature for 8 hours the Mixture is filtered, the filtrate poured into ice water, alkalinized 5 N. the sodium hydroxide solution, extracted with ethyl acetate, dried with magnesium sulfate and evaporated to small volume. The product crystallizes, giving 1.2 g of the desired product, TPL 88-90°C.

(a) 2-(4,6-Dimethoxypyrimidine-2-ylthio)thiophene-3-amine

To a solution of the product from the previous stage (2.2 g) in methanol (30 ml) is added potassium carbonate (1.0 g), the reaction mixture is heated with stirring to 40°C and kept at this t is mperature within 6 hours The mixture is cooled, filtered, the filtrate evaporated, the residue is distilled chromatographytandem (eluent petroleum ether 60-80° - ethyl acetate, 8:2), obtain 1.0 g of the desired product as an orange oil.

(g) 1-Cyano-N-[2-(4,6-dimethoxypyrimidine-2-ylthio)-3-thienyl]methanesulfonamide

A solution of the product from the previous stage (1.2 g) and pyridine (1.0 ml) in methylene chloride (10 ml) cooled to -78°C and with stirring, added dropwise a solution of cyanomethylphosphonate (0.6 g) in methylene chloride (5 ml), maintaining the temperature in the range from -78 to -60°C. the Mixture was stirred at -78°C for 15 min, allowed to warm to room temperature and stirred for 16 h Then the mixture was poured into water and extracted with methylene chloride. The combined extracts are dried with magnesium sulfate, the solvent is evaporated. The solid residue is distilled chromatographytandem (eluent petroleum ether 60 - 80° - ethyl acetate, 8:2), obtain 0.4 g of the desired product, TPL 118-120°C.

EXAMPLE B7

N-[2-(4,6-Dimethoxypyrimidine-2-ylthio)-3-thienyl]-1,1,1-triftormetilfullerenov

A solution of the product from stage (b) of Example B6 (1.0 g) and pyridine (0.6 ml) in methylene chloride (25 ml) cooled to -78°C and with stirring, added dropwise a solution of triftormetilfullerenov anhydride (1.1 g) in methylene chloride (5 ml), maintaining the temperature in the range from -78 to -60°C. a Mixture of AC who're asked at -78° C for 15 min, allowed to warm to room temperature and stirred over night at room temperature. The mixture is then poured into water, extracted with methylene chloride. The combined extracts are dried with magnesium sulfate, the solvent is evaporated. The solid residue is distilled chromatographytandem (eluent petroleum ether 60-80° - ethyl acetate, 8:2), obtain the desired product (BA), TPL 103-104°C, as well as the corresponding compound where the substituent R2represents-SO2CF3(R7), TPL 136-138°C.

EXAMPLE B8

Methods described above can be obtained the following compounds of formula 16 where the substituent R2represents a hydrogen atom; each of the substituents R3and R4represents a methoxy group, and Deputy Q represents-CH2is:

N(Me)
YAndInDR1
CHSSNCHCF3
SNN(Me)SNCHCF3
SNSSNNCF3
SNSNCHCF3
SNSNNCF3
SNN(Me)NCHCF3
SNSNSCHCF3
SNSNN(Me)CHCF3
SNSNN(Me)CHCF3
SNSNSNCF3
SNNSCHCF3
SNNN(Me)CHCF3
SNCClSCHCF3
SNCClN(Me)NCF3
SNCClSNCF3
SNCClN(Me)NCF3
SNCFSCHCF3

continuation
CHCFN(Me NCF3
CHCFSNCF3
CHCFN(Me)NCF3
CHCHCHSCF3
CHCHCHN(Me)CF3
CHNCHSCF3
CHCHNSCF3
CHCHNN(Me)CF3
CHNCHN(Me)CF3
CHCClCHSCF3
CHCClCHN(Me)CF3
CHCClNSCF3
CHCClNN(Me)CF3
CHCFCHSCF3
CHCFCHN(Me)CF3
CHCFNSCF3
CHCFNN(Me)CF3
NSCHCHCF3
NN(Me)CHCHCF3
NSCHNCF3
NSNCHCF3
NN(Me)CHNCF3
NN(Me)NCHCF3
NCHSCHCF3
NCHN(Me)CHCF3
NCHN(Me)CHCF3
NCHSNCF3
NNSCHCF3
NNN(Me)CHCF3
NCClSCH CF3
NCClN(Me)NCF3
NCClSNCF3
NCClN(Me)NCF3
NCFSCHCF3
NCFN(Me)NCF3

continuation
NCFSNCF3
NCFN(Me)NCF3
NSNSNSCF3
NSNSNN(Me)CF3
NNSNSCF3
NSNNSCF3
NSNNN(Me)CF3
NNSNN(Me)CF3
N CClSNSCF3
NCClSNN(Me)CF3
NCClNSCF3
NCClNN(Me)CF3
NCFSNSCF3
NCFSNN(Me)CF3
NCFNSCF3
NCFNN(Me)CF3
SNSSNCHCH2CN
SNN(Me)SNCHCH2CN
SNSSNNCH2CN
SNSNCHCH2CN
SNN(Me)SNNCH2CN
SNN(Me)NCHCH2CN
SNSNS CHCH2CN
SNSNN(Me)CHCH2CN
SNSNN(Me)CHCH2CN
SNSNSNCH2CN
SNNSCHCH2CN
SNNN(Me)CHCH2CN
SNCClSCHCH2CN
SNCClN(Me)NCH2CN
SNCClSNCH2CN
SNCClN(Me)NCH2CN
SNCFSCHCH2CN
SNCFN(Me)NCH2CN
SNCFSNCH2CN

CH2CN N
continuation
SNCFN(Me) CH2CN
SNSNSNN(Me)CH2CN
SNNSNSCH2CN
SNSNNSCH2CN
SNSNNN(Me)CH2CN
SNNSNN(Me)CH2CN
SNCClSNSCH2CN
SNCClSNN(Me)CH2CN
SNCClNSCH2CN
SNCClNN(Me)CH2CN
SNCFSNSCH2CN
SNCFSNN(Me)CH2CN
SNCFNSCH2CN
SNCFNN(Me)CH2CN
NSSNCH
NN(Me)SNCHCH2CN
NSSNNCH2CN
NSNCHCH2CN
NN(Me)SNNCH2CN
NN(Me)NCHCH2CN
NSNSCHCH2CN
NSNN(Me)CHCH2CN
NSNN(Me)CHCH2CN
NSNSNCH2CN
NNSCHCH2CN
NNN(Me)CHCH2CN
NCClSCHCH2CN
NCClN(Me)NCH2CN
NCClSNCH2CN
CClN(Me)NCH2CN
NCFSCHCH2CN
NCFN(Me)NCH2CN
NCFSNCH2CN
NCFN(Me)NCH2CN
NSNCHSCH2CN

N
continuation
NSNSNN(Me)CH2CN
NNSNSCH2CN
NSNNSCH2CN
NSNNN(Me)CH2CN
NNSNN(Me)CH2CN
NCClSNSCH2CN
NCClSNN(Me)CH2CN
NCClSCH2CN
NCClNN(Me)CH2CN
NCFSNSCH2CN
NCFSNN(Me)CH2CN
NCFNSCH2CN
NCFNN(Me)CH2CN

EXAMPLE herbicide activity (pre-emergence)

Seeds of the test species, listed below, are sown in the Cup area of 8.5 cm2filled with sterile loam to 2 cm from the top, and cover with a layer of loam 2-5 mm. cups of water and then treated by spraying on the soil surface following compounds of Examples, drawn up in the form of a solution/suspension in a mixture of acetone and a solution polyoxyethylene (20 moles) of monolaurate (wetting agent, 10 g/l) in a volume ratio of 3:1. The concentration of each test compound and the amount of use I expect to get the desired rate of flow of the compound in 200 l/ha

After 3-4 weeks of growth in the greenhouse (minimum temperature 16°C for species adapted to a temperate climate, 21°C for species Mariposa is slow to moderate the climate, when the duration of the photoperiod 16 h) plants assessed visually to identify any herbicide effect. All differences compared with untreated control assessed on a scale, according to which:

0=no effect,

1=1-24% effect

2=25-69% effect

3=70-89% effect and

4=90-100% of the effect.

To identify the species in the table below uses the following notation:

and Triticum aestivum (wheat)

b - Hordeum vulgare (barley)

in Beta vulgaris (sugar beet)

Mr. Brassica napus (canola)

Dr. Alopecurus myosuroides (Alopecurus mirzahosseini)

e - Avena fatua (wild oat)

W - Elymus repens (couch grass)

C - Bromus sterilis (barren fire)

and Viola arvensis (violet field)

K - Stellaria media (starwort)

l - Galium aparine (cleaver)

m - Matricaria inodora (chamomile odorless)

n - Polygonum lapathifolium (Highlander pale)

o - Veronica persicae (Veronica Persian)

The results are presented below:

td align="center"> 2
Examplekg/haandbingdeWCandtolmnabout
A10.251134131243434
A30.500240000223423
A60.2510341002444434
A70.2510321100343424
A80.12522342122343424
A90.1250122200234 424
A160.12521442221344434
A170.06300130000232322
A1080.500220000222402
A0.500330010433424
A1110.12501110000112303
A1120.125 01210001343413
A0.500220000231313
A0.500220002343434
A0.2511241001344424
B10.501231021223423

EXAMPLE herbicide activity And (post-harvest)

The following plants are grown in a greenhouse (minimalist guest the other temperature 16° For species adapted to a temperate climate, 21°for species not adapted to a temperate climate, with a duration of photoperiod 16 h) in the cups with an area of 8.5 cm2containing sterile loam, and then treated in the chamber for spraying at the stage of 3-4 leaves the compounds of the following Examples, formed in the form of a solution/suspension in a mixture of acetone and a solution polyoxyethylene, (20 moles) of monolaurate (wetting agent, 10 g/l) in a volume ratio of 3:1. The concentration of each test compound and the amount of use I expect to get the desired rate of flow of the compound in 200 l/ha

After 3-4 weeks of growth in the greenhouse the plants is assessed visually to identify any herbicide effect. All differences compared with untreated control assessed on a scale, according to which:

0=no effect,

1=1-24% effect

2=25-69% effect

3=70-89% effect and

4=90-100% of the effect.

To identify the species in the table below uses the same notation as in Example herbicide activity A.

The results are presented below:

Examplekg/haandbthe gdeWCandtolmnabout
ExKg/haandbdefghijklmn
A10.500240000024422
A30.5001 41000124412
A50.511131011212212
A60.2510442222334432
A70.251124 2222333423
A80.2510442020444422
A90.12511340010334422
A160.03211341 000244331
A170.2500440000244431
A0.510441010234423
A111 motorway0.25002310 00003302
A1120.250023000002402
A0.2500020000002000
A0.250014000 0023230
A0.2500441000244222
A0.12500340000034222
A0.12500100000 003030
A0.06310110000002011
B10.501242010033412

ADDITIONAL EXPERIMENTAL DATA

It was found that in addition to the compounds described in this application, the compounds presented in tables 1 and 4 below also apply as herbicides. They are included in the scope of the claims and, thus, additionally confirm announced the initial scope of the invention.

Test 1

Compounds 1-a, 1-b, 1-C and 1-D are presented in table 1 below, feel on herbicide activity against weeds in pre-emergence and post-harvest application in accordance with HERBICIDE EXAMPLES and descriptions. The results are given in tables 2 and 3 below. The results show that the compounds possess valuable herbicide for pre-emergence and/or post-harvest application.

Table 1
The compounds of formula (1)

ConnectionR1QR2R*YLink
1CH2CF3CH-SCH3NFNRefers to paragraph 1 of the invention
1CH3SN-HENFSN Refers to paragraph 1 of the invention
1CH2CICH-och3NFSNRefers to paragraph 1 of the invention
1-DCF3CH-FNFSNRefers to paragraph 1 of the invention
Table 2
Herbicide effect in pre-emergence application
ConnectionDose (Gai/ha)Herbicide activity against
AlEUSEPHSISNGAMAST
175444444444
175222 444444
1753344--343
1-D752334--444
Table 3
Herbicide effect in post-harvest application
ConnectionDose (Gai/ha)Herbicide activity against
AlEUSEPHSISNGAMAST
175222233322
1752 2244444
175232323332

Abbreviations used in tables 2 and 3:

AI=active ingredient

EU=Echinochloa grus-galli

SE=Setaria lutescens

PH=Pharbitis purpurea

SI=Sinapis alba

CP=Chrysanthemum segetum

GA=Gallium aparine

MA=Matricaria inodora

ST=Stellaria media = not tested

All differences from the untreated control assessed in accordance with the index, where 0 is no effect, 1=1-24%, 2=25-69%, 3=70-89%, and 4=90-100% of the action.

S-CH3td align="center"> 2-F
Table 4
The herbicides of the formula (I')
No.R1(R)nR3R4YXSo square (°C)
1CH2CI2-CIOCH3OCH8NS-C6H558-62
2CH2Cl4-NO2 OCH3NS-C6H580-82
3CH2Cl2-SNONOCH3NS-C6H5resin
4CH3CF32-FOCH3OCH3NS-C6H556-60
5CH2CF32,4-F2OCH3OCH3NS-C6H581-84
6CH2CF34-NO2OCH3OCH3NS-C6H5resin
7CH2Cl2,4-F2OCH3OCH3NS-C2H5122-123
8CF32,4-F2OCH3OCH3NS-C6H572-82
9CH32-FOCH3OCH3NS-CH3resin
10SN2,4-F2OCH3OCH3NS-CH3resin
11CH32-SONOCH3OCH3Nresin
12CH2Cl2-FOCH3OCH3SNS-CH3resin
13CH2ClNOCH3OCH3NS-CH3resin
14CH2Cl2-FOCH3OCH3NS-CH3resin
15CH2Cl2,4-F2OCH3OCH3NS-CH3resin
16CH2Cl4-NO2OCH3OCH3NS-CH3137-140
17CH2Cl4-OCF3OCH3OCH3NS-CH3resin
18CH2Cl2-SNOCH3OCH3NS-CH3158-161
19CH2Cl2-ONOCH3OCH3NS-CH3124 to 128
20CH2Cl2-SOSOCH3OCH3NS-CH3resin
21CH2Cl3-CF3OCH3OCH3NS-CH3resin
22CH2CF32-FOCH3OCH3SNS-CH3resin
23CH2CF82-ClOCH3OCH3NS-CH3115-117
24CH2CF32,4-F2OCH3OCH3NS-CH3resin
25CH2CN2-FOCH3OCH3SNS-CH3147
26CF32-FOCH3OCH3NS-CH3143
29CF34-OCF3OCH3OCH3NS-CH372-75
30SNSN2-FOCH3OCH3SNS-CH3resin
31SNSN2-FOCH3OCH3NS-CH372-77
32NHCO2CH3OCH3OCH3SNS-CH3113-115
33CH2Cl2-FOCH3OCH3SNHE153 to 155
34CH2CF32-FOCH3OCH3SNHE143-145
35CH2CN2-ClOCH3OCH3SNHE172 (decomp)
36CF32-FOCH3OCH3SNHE94-96
37CF32-ClOCH3OCH3SNHE120
38SN2-FOCH3OCH3SNHE153-154

All compounds are presented in table 4 above shall be given in accordance with the methods described in this invention. These compounds also have a weed-killing effect in pre-emergence and post-harvest application.

Tested compounds exhibit herbicide activity rating from "good" to "excellent" (70 to 100% compared to control) about the wearing of important species of weeds, such as:

Sinapis alba,

Matricaria inodora,

Chrysanthemum segetum,

Avena sativa

Stellaria media,

Echinochloa crus-galli,

Lolium Polygonum,

Setaria spp,

Abutilon theophrasti,

Amaranthus retroflexus and

Panicum miliaceum

when pre-emergence application in a dose of 0.5 kg and less of active ingredient per hectare.

In addition, the tested compounds possess herbicide activity with rating from "good" to "excellent" with regard to important species of weeds, such as:

Sinapis alba,

Echinochloa crus-galli,

Lolium rnultrflorum,

Matricaria inodora,

Chrysanthemum segetum,

Setaria spp.,

Abutilon theophrasti,

Amaranthus retroflexus,

Panicum miliaceum and

Avena sativa

when post-harvest application in a dose of 0.5 kg and less of active ingredient per hectare.

From the above additional data shows that the claimed amount of claims for compounds of formula (I) is sufficiently substantiated and fully vindicated, and that the aryl group can be substituted by various substituents without loss of useful herbicide action. In addition, the substituents X on the bridge SHH may be modified within the scope of paragraph 1 to include X or X', which represent phenylthio, alkylthio, alkoxy, halogen, hydroxy, etc. their derivatives (or precursors), such as phenoxy.

ADDITIONAL EXPERIMENTAL DATA

We studied the herbicides of the formula (I')

where

No.R1(R)nR3R4YXT Deputy (°)
I'-CHF2-Och3Och3SNHE103-105
I'-bCHF22-CH2-Och3Och3Och3SNHE76-77
I'-CHF22-CH2-CH3Och3Och3SNHE120-121

The compounds shown in the table, obtained by the method presented in the application.

Compounds were tested in field conditions on herbicide activity against weeds typical of the rice fields.

Test conditions and results.

Weed seeds were sown in the soil under a layer of water of thickness 3 see compound used in the form of standard compositions are water-based. After treatment of the plants they were kept for 28 days in greenhouse conditions. After that, the weeds were evaluated by comparing with the control (untreated the s plants). The results are presented below.

Dose

Connection (grams of active ingredient/ha)
Herbicide action (KPI) against
EUMOSC
I'-250555
65455
15355
I'-b250555
65555
15555
I'-250555
65555
15555

Designation

EC=Echinochloa oryzicola

MO=Monoochoria vaginalis

SC=Scirpus juncoides

Efficiency connected the th is expressed using the scale:

0=no effect 9% effect;

1=10-29%;

2=30-49%

3=50-69%

4=70-89%;

5=90-100% effect.

Under the effect refers to the difference in the number of weeds in the processing and control compared to control.

1. The sulfonamides of the formula

and their salts, where

And represents a substituted or unsubstituted benzene ring or 5-membered or 6-membered substituted or unsubstituted heteroaromatic ring, selected from the group comprising thienyl, pyrazolyl, imidazolyl, pyridyl, where the optional substituents selected from the group consisting of halogen, unsubstituted or substituted alkyl containing 1-4 carbon atoms, unsubstituted or substituted alkoxy containing 1-4 carbon atoms, nitro, phenyl, phenoxy, benzoyl and alkylcarboxylic containing 1-4 carbon atoms in the alkyl fragment, when any alkyl fragment in the last mentioned substituents substituted by one or more halogen atoms, alkoxygroup containing 1-4 carbon atoms, cyano and phenyl;

Q represents-O-, -S - or a group of the formula-SHH';

X and X', which may be the same or different, are each hydrogen, halogen, cyano, alkyl containing 1-8 carbon atoms, or a group-ORa, -SRaor one of X and X' submitted is a hydroxy, and the other takes the values defined above;

Rarepresents alkyl containing 1-8 carbon atoms, or phenyl;

Rbrepresents alkyl containing 1-8 carbon atoms, or phenyl;

Y represents nitrogen or the group CR9;

R1represents alkyl containing 1-8 carbon atoms, unsubstituted or substituted with halogen, cyano, phenyl or alkoxycarbonylmethyl containing 1-4 carbon atoms in the alkyl part, or represents phenyl;

R2represents hydrogen or alkyl containing 1-4 carbon atoms;

R3and R4that may be the same or different, are each alkyl containing 1-4 carbon atoms, alkoxygroup containing 1-4 carbon atoms, or halogen;

R9represents hydrogen,

provided that when Q represents O or S, the ring a represents a 5-membered substituted or unsubstituted heteroaromatic ring as defined above.

2. The sulfonamide according to claim 1, where R1represents methyl, chloromethyl, methyl bromide, cyanomethyl or trifluoromethyl.

3. The sulfonamide according to claim 1 or 2, where R2represents hydrogen.

4. Sulfonamides according to any one of claims 1 to 3, where R3represents methyl, methoxy-what the Republican or chlorine, and R4represents a methyl or methoxy group.

5. Sulfonamides according to any one of claims 1 to 4, where a represents a phenyl, optionally substituted by F, Cl, Br, stands or methoxy group, or represents pyrazolyl substituted by one or more metal groups.

6. Sulfonamides according to any one of claims 1 to 5, where Q represents CH2.

7. Herbicide composition containing from 0.01 to 99 wt.% one or more compounds of the formula (I) according to any one of claims 1 to 6 and 1-99,99 wt.% a suitable carrier and/or surface-active substances.

8. Method of controlling weeds in areas littered with weeds or assume their appearance, comprising applying to the specified area of an effective amount of one or more compounds according to any one of claims 1 to 6.

9. The method of obtaining sulfonamida formula I according to claim 1 in which the ring a is a phenyl, which may have 1-2 substituent selected from a halogen atom, lower alkyl, lower alkoxyl, or represents an unsaturated five-membered a heterocycle with the sulfur atom, or two nitrogen atoms and which can be substituted by two lower alkilani, R1represents a lower alkyl group, substituted by halogen atoms, cyano, R2represents hydrogen, Q represents-S-group (CH2)n, which may be substituted by lower what Kilom, n=1 or 2, R3and R4are the same and represent the lowest alkoxygroup, Y represents nitrogen or the group CR9where R9represents hydrogen, including the interaction of the compounds of formula II

where the values of A, R1, R2, Q, n, R3, R4, Y the above, with a sulfonic anhydride of formula (R1SO2)2O or sulphonylchloride formula R1SO2Hal, where Hal represents halogen.



 

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61 cl, 1 tbl, 5 ex

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10 cl, 3 tbl, 1 sch, 12 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of carboxylic acids of the formula: wherein Y is taken independently in each case among the group comprising C(O), N, CR1, C(R2)(R3), NR5, CH; q means a whole number from 3 to 10; A is taken among the group comprising NR6; E is taken among the group comprising NR7; J is taken among the group comprising O; T is taken among the group comprising (CH2)b wherein b = 0; M is taken among the group comprising C(R9)(R10), (CH2)u wherein u means a whole number from 0 to 3; L is taken among the group comprising NR11 and (CH2)n wherein n means 0; X is taken among the group comprising CO2H, tetrazolyl; W is taken among the group comprising C, CR15 and N; R1, R2, R3 and R15 are taken independently among th group comprising hydrogen atom, halogen atom, hydroxyl, alkyl, alkoxy-group, -CF3, amino-group, -NHC(O)N(C1-C3-alkyl)-C(O)NH-(C1-C3-alkyl), -NHC(O)NH-(C1-C6-alkyl), alkylamino-, alkoxyalkoxy-group, aryl, aryloxy-, arylamino-group, heterocyclyl, heterocyclylalkyl, heterocyclylamino-group wherein heteroatom is taken among N atom or O atom, -NHSO2-(C1-C3-alkyl), aryloxyalkyl; R4 is taken among the group comprising hydrogen atom, aryl, aralkyl, benzofuranyl, dihydrobenzofuranyl, dihydroindenyl, alkyl, benzodioxolyl, dihydrobenzodioxynyl, furyl, naphthyl, quinolinyl, isoquinolinyl, pyridinyl, indolyl, thienyl, biphenyl, 2-oxo-2,3-dihydro-1H-benzimidazolyl, pyrimidinyl and carbazolyl. Other values of radicals are given in the claimed invention. Also, invention relates to pharmaceutical composition used for inhibition binding α4β1-integrin in mammal based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof in aims for treatment or prophylaxis of diseases associated with α4β1-integrin.

EFFECT: improved method for inhibition, valuable medicinal properties of compounds.

33 cl, 7 tbl, 42 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to new taxanes of the general formula (I)

wherein R2 means benzoyloxy-group; R7 means hydroxyl (OH); R9 means keto-group; R10 means R10aCOO-; R10 means (C2-C6)-alkyl, (C2-C6)-alkenyl, (C3-C6)-cycloalkyl or 5-6-membered heteroaromatic group wherein heteroatom represents oxygen atom (O), sulfur atom (S) or nitrogen atom (N); R14 means hydrogen atom (H); X3 means (C2-C6)-alkyl, (C2-C6)-alkenyl, (C3-C6)-cycloalkyl, phenyl substituted possibly with nitro-group (-NO2), 5-6-membered heteroaromatic group wherein heteroatom represents O, S or N; X5 means -COX10, -COOX10; X10 means (C2-C6)-alkyl, (C2-C6)-alkenyl, (C3-C6)-cycloalkyl, phenyl or 5-6-membered heteroaromatic group wherein heteroatom represents O, S, N; Ac means acetyl. Compounds of the formula (I) elicit antitumor activity.

EFFECT: valuable medicinal properties of compounds.

68 cl, 1 tbl, 6 ex

Chalcone coumarins // 2266291

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): or their pharmaceutically acceptable salts or solvates wherein Ar represents a substituted or unsubstituted (preferably aromatic one) carbocyclic or heterocyclic group wherein abovementioned carbocyclic or heterocyclic group comprises 5 or 6 atoms in cyclic structure wherein a heteroatom is taken among the group consisting of nitrogen (N) and sulfur (S) atom and any substitutes at Ar group are taken independently of one another of the group consisting of Cl, Br, F atoms and OR10 wherein R10 represents saturated or unsaturated lower hydrocarbon (C1-C6)-radical of normal or branched structure; R represents OR10 wherein R10 corresponds to above given value; R1 represents lower hydrocarbon (C1-C6)-radical of normal or branched structure under condition that if R1 represents -CH3 and R means -OCH3 or -OH then Ar group can't represent 4-methoxyphenyl or 3,4-dimethoxyphenyl. Also, invention proposes a component of medicinal agent used in treatment or prophylaxis of neoplasms. Also, invention proposes a pharmaceutical composition possessing with an anti-proliferative activity and comprising the effective amount of one or some compounds of the formula (I) in combination with one or some pharmaceutically acceptable additives. Invention provides the development of chalcone coumarins possessing with the enhanced anti-proliferative effect with respect to sensitive tumor cells, cells with resistance to conventional chemotherapeutic agents, among them, to anti-tumor medicinal agents of the last generation represented by paclitaxel and docetaxel.

EFFECT: valuable medicinal properties of compounds and compositions.

1 tbl, 21 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of imidazole of the formula (I):

or its pharmaceutically acceptable salts wherein X represents -CH2-(CH2)p-, -O-; R1 represents phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, (C3-C7)-cycloalkyl wherein indicated phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, (C3-C7)-cycloalkyl are substituted optionally with 1-3 substitutes taken independently among halogen atom, -OH, halogen-(C1-C6)-alkyl, (C1-C6)-alkyl, (C1-C6)-alkoxy group and OH-(C1-C6)-alkyl; R2 represents hydrogen atom (H) or (C1-C6)-alkyl; R3 represents H or (C1-C6)-alkyl; R4 represents H or (C1-C6)-alkyl; R5 represents H, or R5 and R7 form in common a bond; each R6 represents independently halogen atom, -OH, halogen-(C1-C6)-alkyl, (C1-C6)-alkyl, (C1-C6)-alkoxy group or OH-(C1-C6)-alkyl; R7 represents H, or R7 and R5 form in common a bond; each R8 represents independently -OH, (C1-C6)-alkyl, halogen-(C1-C6)-alkyl or (C1-C6)-alkoxy group; m = 0, 1, 2 or 3; n = 0 or 1; p = 0 or 1; r = 0 or 1; t = 0. Also, invention relates to a method for preparing compounds of the formula (I) and to a pharmaceutical composition showing affinity to alpha-2-adrenoceptors based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof used in aims for treatment of neurological disturbances, psychiatric disorders or disturbances in cognitive ability, diabetes mellitus, lipolytic diseases, orthostatic hypotension or sexual dysfunction.

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

25 cl, 1 tbl, 14 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to benzimidazole derivatives or their salts useful in medicine of the general formula (1): wherein R1 and R2 can comprise similar or different values and represent independently of one another hydrogen atom, halogen atom, cyano-group, hydroxyl group, alkyl group comprising 1-4 carbon atoms, alkoxy-group comprising 1-4 carbon atoms, trifluoromethyl group; A represents unsubstituted, linear alkylene group comprising 1-7 carbon atoms; E represents group -COOR3 comprising 1-6 carbon atoms; G represents unsubstituted, linear alkylene group comprising 1-6 carbon atoms; M represents a simple bond or -S(O)m- wherein m represents a whole number in the range 0, 1 or 2; J represents substituted or unsubstituted heterocyclic group comprising 4-10 carbon atoms and one heteroatom in ring taken among the group consisting of nitrogen atom or sulfur atom excluding unsubstituted pyridine ring; a substitute in indicated aromatic heterocyclic group is taken among halogen atom, cyano-group, linear alkyl group comprising 1-6 carbon atoms, linear alkoxy-group comprising 1-6 carbon atoms, trifluoromethyl group and trifluoromethoxy-group wherein one or more indicated substituted can be replaced by random positions in ring; X represents methane group (-CH=). Also, invention relates to a pharmaceutical composition used in inhibition of human chymase activity based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof in aims for prophylaxis and/or treatment of inflammatory disease, cardiovascular disease, allergic disease, respiratory disease or osseous either cartilaginous metabolic disease.

EFFECT: valuable medicinal properties of compounds and composition.

14 cl, 3 tbl, 20 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to new 5-aryl-1-phenyl-4-heteroyl-3-hydroxy-3-pyrroline-2-ones of the formula:

wherein (1) X means sulfur atom (S); R means (CH3)2CH; (2) X means sulfur atom (S); R means (CH3)3C; (3) X means oxygen atom (O); R means (CH3)3C. Compounds of the formula (I) are prepared by interaction of the corresponding heteroylpyruvic acid methyl ester with mixture of aniline and aromatic aldehyde in acetic acid medium at short-time heating. Compounds elicit an anti-bacterial activity with value MIC = 3.9-7.8 mcg/ml as compared with 62-1000 mcg/ml for analogue.

EFFECT: valuable properties of compounds.

1 tbl, 3 ex

The invention relates to organic chemistry and can find application in medicine

The invention relates to imidazole derivative of the formula (I), where X, Y, R, R2, R3and R4such as defined in the claims

The invention relates to imidazole derivative of formula (1), where X, Y, R, R2, R3and R4such as defined in the claims

The invention relates to new derivatives of azetidine formula

in which R denotes an element of the formula

R1denotes a methyl radical or ethyl, R2denotes a naphthyl radical, hinely, phenyl, possibly substituted by one or more halogen atoms, alkyl radicals, alkoxyl, hydroxyl, etc.,, R3and R4identical or different, represent a phenyl radical, possibly substituted by one or more halogen atoms, alkyl, alkoxyl, formyl, trifluoromethyl, etc.,, R5denotes an alkyl radical or phenyl, substituted by one or more halogen atoms, R6and R7identical or different, denote a hydrogen atom or an alkyl radical, or R6and R7together with the nitrogen atom to which they are connected, form piperidinyl or pieperazinove cycle, substituted alkyl, R’6and R’7identical or different, denote a hydrogen atom or an alkyl radical, or R’6and R’7together with the nitrogen atom to which they are connected, form a pyrolidine or pieperazinove cycle, possibly substituted by one alkyl radical, cycloalkyl, -ALK-O-ALK, hydroxyalkyl, or R6and R7together with the nitrogen atom to which they are connected, form a loop imidazole, piperazinone, thiomorpholine, etc., R8denotes alkyl, R9denotes a hydrogen atom, an alkyl radical or an alkyl, substituted dialkylamino, phenyl, etc.,, R10and R11identical or different, denote a hydrogen atom or alkyl, R12and R13together with the nitrogen atom to which they are connected, form a loop of the research, a R16and R17together with the nitrogen atom to which they are connected, form a loop of piperidine, R’ denotes a hydrogen atom or the radical-CO-ALK, ALK denotes an alkyl or alkylene, and alkyl or alkylene radicals or their parts and CNS radicals or their parts are straight or branched chain, containing from 1 to 6 carbon atoms, and their optical isomers and their salts with mineral or organic acid

The invention relates to inhibitors tyrosinekinase type bis-indolylmaleimide compounds of the formula I

< / BR>
where Z denotes a group of General formula II

< / BR>
where A, B, X, Z, R1-R10have the meanings indicated in the claims, as well as the way they are received and drug based on these compounds

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of urea of the formula (I): wherein A means heteroaryl that is taken among the group that comprises: and wherein radicals B, R1 and R2 have values given in description. These compound possess capacity to inhibit activity of enzyme RAF kinase and to inhibit growth of tumor cells. Also, invention relates to a method for inhibition of activity of RAF kinase in mammal body and to pharmaceutical compositions based on compounds of the formula (I). Invention provides preparing new derivatives of urea possessing valuable pharmaceutical properties.

EFFECT: improved method for inhibition, valuable properties of compounds and composition.

25 cl, 6 tbl

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