Derivatives of imidazoline and method of production thereof

 

(57) Abstract:

Available ortho-carboxy-/5-oxo-2-imidazolin-2 - yl/benzoheterocycles compounds, in which the condensed heterocyclic ring system is a 5-element ring containing one, two or three nitrogen atom, derivatives of the aforementioned heterocyclic compounds and how they can be applied for the destruction of monocotyledonous and dicotyledonous plant species. 2 S. p. f-crystals, 5 PL.

Some imidazolines benzoic and naphthoic acids, esters and salts, their use as herbicide agents proposed in U.S. patents NN 4 188 487; 4 297 128 and 4 554 013, and in the patent application UK N 2 172 866 A and European patent application 86200304.3. However, imidazolines benzazolyl of the present invention is not described nor suggested in the above patents and patent applications. Connection with the condensed heterobasidion and herbicide use is described in U.S. patent No. 4 650 514 and 4 752 323. Although there are a large number herbicide active imidazolinone compounds are much more effective imidazolinone compounds would be useful for farmers, agronomists, entrepreneurs, and for controlling undesirable plants is zainil ortho-carboxy-2-benzoheterocycles connection and indolocarbazoles diones for the destruction of a variety of monocotyledonous and dicotyledonous plant species such as those species that are in General very difficult to destroy in agricultural practice.

The invention relates to 2-/2-imidazolin-2-yl/benzoheterocycles compounds, which have the following structure:

< / BR>
in which: R1is hydrogen, CI/C1-C4/ alkylamino,

C1-C12the alkyl may be substituted by one to three substituents: C1-C4alkoxy, C1-C4alkylthio, halogen, hydroxy, C1-C4cycloalkyl, benzoyloxy, fullam, phenyl, possibly substituted by nitro, one to three halogen, C1-C4alkyl groups or C1-C4alkoxy groups, carboxy, C1-C4alkoxycarbonyl, cyano or three/C1-C4/ alkylammonium a halide;

C3-C12alkenyl may be substituted by one to three substituents: C1-C4alkoxy, phenyl, halogen or C1-C4alkoxycarbonyl;

C3-C6cycloalkyl, can be substituted one to three C1-C4alkyl groups;

C3-C16the quinil may be substituted by one to three halogen or a cation;

R2is C1-C4by alkyl;

R3is e carbon to which they are attached, they may represent C1-C4cycloalkyl possibly replaced by stands;

B is hydrogen, COR4or SO2R5with the proviso that when B is COR4or SO2R5, R1is other than hydrogen or a cation, and R9different from hydrogen;

R4is C1-C11the alkyl, chlorochilon or phenyl, possibly substituted with halogen, nitro or C1-C4by alkyl;

R5is C1-C4the alkyl or phenyl, possibly substituted C1-C4by alkyl;

X, Y and Z each independently is CR6, CR7R8, N or NR9with the proviso that at least one of X, Y and Z must be N or NR9;

configuration is either a simple bond or double bond with the proviso that when any of X, Y or Z is CR7R8or NR9then === configuration, attached to it, is a simple connection, with one proviso that at least one of the === configuration represents a simple bond;

R6, R7and R8are independently hydrogen, halogen, C1-C4alkoxy or C1-C4the alkyl may be substituted od and;

R9is hydrogen or C1-C4the alkyl possibly substituted by hydroxy or one to three halogen, C1-C4alkoxy groups, or C1-C4alkylthio groups;

Q is hydrogen, halogen, C1-C4alkoxy or C1-C4the alkyl, possibly substituted by one to three of the following substituents: halogen, C1-C4alkoxy, C1-C4alkylthio or C2-C4alkenyl;

their optical isomers, when R2and R3not the same or when R7and R8unequal;

their tautomers and geometric isomers, and their attached salts of acids, except when R1is salabrasion cation.

In addition, in accordance with the present invention provides methods of obtaining the above-mentioned compounds and methods for the destruction of undesirable monocotyledonous and dicotyledonous plant species by means of their application.

The invention relates to 2-/2-imidazolin-2-yl/benzoheterocycles compounds having the structure:

< / BR>
in which R1is hydrogen, CI/C1-C4/alkylamino,

C1-C12the alkyl, possibly substituted by one to three of sometimes.ilike, fullam, phenyl, possibly substituted with one nitro, one to three halogen, C1-C4alkyl groups or C1-C4alkoxy groups, carboxy, C1-C4alkoxycarbonyl, cyano or three/C1-C4/alkylammonium a halide;

C3-C12alkenyl, possibly substituted by one to three substituents: C1-C4alkoxy, phenyl, halogen or C1-C4alkoxycarbonyl;

C3-C6cycloalkyl, possibly substituted with one to three C1-C4alkyl groups;

C3-C16the quinil, possibly substituted by one to three halogen or a cation;

R2is C1-C4by alkyl;

R3is C1-C4the alkyl or C3-C6cycloalkyl, and when R2and R3taken together with the carbon atom to which they are attached, they may represent C3-C6cycloalkyl possibly replaced by stands;

B is hydrogen, COR4or SO2R5with the proviso that when B is COR4or SO2R5is other than hydrogen or a cation, and R9different from hydrogen;

R4is C1-C11the alkyl, chlorochilon or phenyl, vosmom or phenyl, possibly substituted C1-C4by alkyl;

X, Y and Z each independently is CR6, CR7R8, NR9or N with the proviso that at least one of X, Y or Z is N or NR9;

configuration is either a simple bond or double bond with the proviso that when any of X, Y or Z is CR7R8or NR9then === configuration, attached, represents a simple bond, and on another the proviso that at least one of the === configuration represents a simple bond;

R6, R7and R8independently are hydrogen, halogen, C1-C4alkoxy or C1-C4the alkyl possibly substituted with one hydroxy or one to three halogen, C1-C4alkoxy groups, or C1-C4alkylthio groups;

R9is hydrogen or C1-C4the alkyl possibly substituted with one hydroxy or one to three halogen, C1-C4alkoxy groups, or C1-C4alkylthio groups;

Q is hydrogen, halogen, C1-C4alkoxy or C1-C4the alkyl, possibly substituted by one to three of the following substituents: halogen, C1-C4alkoxy, C1-C47and R8unequal;

the tautomers and geometric isomers, and their attached salts of acids except when R1is a salt-forming cation.

The term "halogen" means F, Cl, Br, or I. the Term cation as used in this patent application and the claims, refers to alkali metals, alkaline earth metals, manganese, copper, iron, zinc, cobalt, lead, silver, Nickel, ammonium or organic ammonium. For alkali metals include sodium, potassium and lithium. Among cations of organic ammonium suitable for use in accordance with the present invention are monoalkylammonium, dialkylammonium, trialkylamine, tetraalkylammonium, monoalkylammonium, dialkylammonium, trialkanolamines, monoalkylammonium, dialkylammonium, monoalkanolamines, dialkanolamines, C5-C6cycloalkylcarbonyl, piperidine, morpholine, pyrrolidine, benzyl ammonium, etc.

Among the ortho-carboxy-/5-oxo-2-imidazolin-2-yl/benzoheterocycles described in accordance with the present invention, use ortho-/2-imidazolin-2-yl/intolerability, ortho-/2-imidazolin-2-yl/Indaselassie, ortho-/2-imidazolin-2-yl/benthem bodymist in agronomic practices in a more effective herbicide agents and in particular, effective herbicide agents that can be used in the presence of important crops so as not to cause harm to the aforementioned plants. Without adequate control of undesirable plant species can destroy or reduce crop yields, reduce the quality and value of the crop, and reduce the efficient production and harvesting. Herbicide imidazolinone benzoheterocycles which is the subject of the present invention have the properties of effective control of a variety of undesirable monocotyledonous and dicotyledonous plant species, and, in addition, demonstrate good selectivity relative to the valuable broadleaf crops such as soybeans and sugar beets.

Herbicide active imidazoline benzoheterocycles compounds having the structure

< / BR>
in which B is hydrogen, and R1, R2, R3X, Y, Z have already been defined above, can be obtained from their previous imeniteloi compounds having the structure of formula I:

< / BR>
Nitrile groups in the compounds of formula I can be hydrolyzed in the presence of sulfuric acid to obtain the corresponding amides, and the resulting alcoholate alkali metal, to obtain the intermediate compounds of diamide of ester of the formula II and their regioisomers. Diamides of ester of the formula II can be converted into the target compounds having structure a or b, the result of the interaction of pentachloride phosphorus in the presence of a solvent. In the case when R6, R7, R8or R9contain one or more exigrep, these actigraphy turned into chlorine group in this reaction. This reaction sequence is illustrated by the flowsheet I.

< / BR>
The regioisomers can be separated using standard chromatographic techniques such as reversed-phase liquid chromatography.

Alternatively, compounds having structure a and b, above, and in which R1is hydrogen, can be obtained in two stages as a result of interaction of the corresponding phthalic anhydride with aminoamides formula III in the presence of a base such as triethylamine, and not necessarily in the presence of a solvent, to obtain the intermediate compounds of diamide acids and their regioisomers, and ring closure of the above intermediate compounds in water under alkaline meta is the new acid, having structure a or b, and their regioisomers, as shown in process scheme II.

< / BR>
The regioisomers can be separated using standard chromatographic techniques such as reversed-phase liquid chromatography.

Another method of preparing compounds of structure a or b, described above, in which R1and B are hydrogen, similar to the method proposed in U.S. patent No. 4 758 667, according to which complex fluids of formula IV is treated with an alcoholate of an alkali metal such as tration.-butyl potassium and aminoamides formula III in the presence of an inert solvent such as xylene, and then treated with an aqueous acid to obtain the target imidazolines benzoheterocycles, as shown in scheme III, where R10is C1-C8the alkyl.

< / BR>
Compounds having the structure of c and d can be obtained from the appropriate onignition formula I by acid hydrolysis of the nitrile groups to obtain the appropriate kidney, and their cyclization in the presence of alkali metal hydride such as sodium hydride, to obtain the target indolocarbazoles diones, as shown in technorama, and B is hydrogen, can be obtained from compounds having the structure c or d as a result of interaction of the above compounds with an appropriate nucleophile such as an alcoholate of an alkali metal, as shown in the flowsheet V.

< / BR>
Compounds having the structure e or f, can be obtained as a result of interaction ortho-/2-imidazolin-2-yl/benzoheterocycles carboxylic acid having structure a or b, in which B is hydrogen, dicyclohexylcarbodiimide (DCC) in the presence of nevroticheskogo solvent, as shown in process scheme VI.

< / BR>
Connection structures c and d in which Z is NR9or N, X and Y are CH, and Q is hydrogen, can be obtained from the corresponding 3-vinylpyrrole through education appropriate kentrilogia intermediate compounds of the formula I in the reaction Delta-Adler with appropriately substituted maleimido nitrile of formula V, and subsequent oxidation using an oxidizing reagent, known in this technical field, such as manganese dioxide, to provide the necessary oxidation state. Education 3-vinylpyrrolidone the source material of the formula I can be converted into the target indolocarbazoles diones of the formula VI in the sequence reaction, described above and illustrated in the flowsheet IV. The reaction scheme shown below technological scheme VII.

< / BR>
And as mentioned above, diones of the formula VI can be converted into the corresponding imidazolines benzoheterocycles structures a and b, as shown in the flowsheet V in which Z is NR9or N, X and Y are CH2and B and Q are hydrogen.

Similarly, compounds having structure a, b, c and d, in which X is NR9or N, Y and Z are CH2and B and Q are hydrogen, can be obtained from 2-pyrrol-carboxaldehyde by repetition of the sequence of reactions shown in the flow charts VII and V, respectively, as shown below.

< / BR>
Compounds having structure a, in which X and Y are N or NR9Z is CR6and B and Q are hydrogen, is obtained from 2-keto-1,3-cyclohexandione as follows: the condensation of the above dione with an appropriately substituted hydrazine provides 1,3-disubstituted dihydroindole formula VII; processing the intermediate compounds of formula VII with sodium hydride and ethylcarbonate gives tetrahydroindazole-5-carboxylate of the formula is the formation gives dihydro-4-cyanoindole-5-carboxylate of formula IX; dehydrogenate the compounds of formula IX and the subsequent treatment of the reaction product hydrogen bromide and acetic acid gives 1,3-dimethyl-1H-indazol-4,5-dicarboxylic acid; treatment with acetic anhydride provides the corresponding anhydride, which can regiospecificity subjected to gap the rings, using the appropriate aminoamide formula III in the target imidazolines benzoheterocycles having the structure a, as is confirmed in the technological scheme II. The reaction sequence is illustrated in the flowsheet VIII (see the end of the description).

Imidazolines indazols having structure b, in which X is CR6and Y and Z are N or NR9can be obtained from digital from an appropriately substituted ketoaciduria, as shown in process scheme IX (see below).

Condensation dimethylacetal, appropriately substituted ketoaciduria with the appropriate hydrazine followed by treatment with acid gives 1,5-dvuhkamernyi pyrazole, as shown. The processing of the above pyrazole with phosphorus oxychloride and dimethylformamide (DMF) and after the reaction the Wittig get vinylphenol formula Hafir formula XI, which then turned into a product imidazolines of indazole using the procedure illustrated in the flowsheet III.

Ortho-imidazolines benzimidazolecarboxylate having structure a and b, can be obtained from their total previous connection, 4-carboxamidine, which is obtained from the acylation of 4-aminophthalate. Using the nitration procedure described by R. L. Williams and C. U. Chalabi in the Journal of Heterocyche Chemistry, 1973, /10/, 891 receive the intermediate compounds of formula XII and XIII. Separation of compounds XII and XIII perform using fractional recrystallization. Hydrogenation of compound XIII with subsequent cyclization of the resulting aminoaniline gives, in primary forms benzimidazole of the formula XIV. Complex fluids of formula XIV can be directly converted into imidazolines the benzimidazole structures a and b, using the techniques described above, and technological schemes II and III. Alternatively, complex fluids of formula XIV can be subjected to alkylation with a suitable alkylhalides to get benzimidazolecarboxylate formula XV, which in turn target imidazolines a benzimidazole having the structure of a and b by means of the procedure shown in the flow charts II environmental scheme X (see at the end of the description).

Similarly, the intermediate compound of formula XII can be converted into ortho-imidazolidinethione carboxylate of formula XVI and XVII, as shown in process scheme XI (see end of opisanie).

Connection imidazolines benzimidazole, in which R6is hydrogen, can be obtained from compounds of formula XIII using sequential acid hydrolysis of amide groups and nitrogroup reduction through the catalytic hydrogenation, to obtain the diamine of formula XVIII. As a result of processing of the diamine with formic acid and azeotropic removal of water get benzimidazole, in primary forms formula XIX, which is then directly converted into the target compounds having structure a or b, in which X and Y are N and Y is CH or complex fluids of formula XVIII is subjected to alkylation, as described above, and the substituted benzimidazole, in primary forms converted into the target compounds having structure a or b, in which X and Z are N or NR9and Y is CH. Transformation of dicarboxylates in the final imidazolines the benzimidazole shown in the flow charts II and III, and the reaction sequence, starting with compounds of formula XIII, shown newstory a, and b, in which X, Y and Z are independently N or NR9receive by using a diamine of the formula XVIII. The reaction of the above-mentioned diamine with solidities in the presence of acetic acid gives complex fluids of benzotriazole formula XX, which is then converted into the target compounds having structure a and b, in which X, Y and Z are N or NR9using the procedure described above for compound diesters benzimidazole of the formula XIV and XIX. This reaction scheme is illustrated by the flowsheet XIII (see the end of the description).

Of course, all the connections described above, having structure a or b, in which R1and B are hydrogen, can be converted into the corresponding imidazolines indolocarbazoles dione having the structure e and f, by repetition of the procedure illustrated in technological scheme VI. Appropriate imidazolines indolocarbazoles dione having the structure c and d, can be obtained by the interaction of the above imidazoline of benzoheterocycles with the anhydride of the acid, not necessarily in the presence of a solvent, as shown in process scheme XIV.

< / BR>
Compounds having structure a or b, in which R1ex is set obtained through the interaction of the compounds, having structure a or b, in which R1is other than hydrogen or a cation, R9different from hydrogen, and B is hydrogen, acylhalides such as acylchlorides or sulfonylamides such as sulfonyl chloride, to obtain the target products in which B is a COR4or SO2R5. The reaction is shown in the flowsheet XV (see the end of the description).

Alternatively, compounds having structure a, or b, in which R1is other than hydrogen or a cation, R9different from hydrogen, and B is a COR4can be obtained by the interaction of compounds having structure a or b, in which R1is other than hydrogen or a cation, R9different from hydrogen, and B is hydrogen, with an acid anhydride of the formula /R4CO/2O.

Imidazolines benzoheterocycles compounds of the present invention are highly effective in destroying a variety of undesirable monocotyledonous plant species such as just plushie, Alopecurus, nymphalinae, sedge, wild oat, onion, etc. and dicotyledonous plant species such as bindweed, Matricaria, morning glory, mustard field, ragweed high, limnocharis, etc. Destroyed what about the invention to the foliage of the aforementioned plants or to soil or water, containing seeds or other means of reproduction in a dose of from about 0,016 to 4.0 kg/ha

Unexpectedly, it was found that some compounds of the present invention are well tolerated broad-leaved cultivated plants such as soybeans and sugar beets when the above compounds are applied to the foliage of the above crops or to soil containing seeds or other means of reproduction in a dose of from about 0,016 up to 1,000 kg/ha

Soybeans play an increasing role as a source of high quality protein and are the most important food legumes, received currently. Sugar beet is the main source of sugar in North America, approximately one third of the sugar consumed here, derived from sugar beets. In Europe, sugar beet is the main source of refined sugar. Using a combination of weed control and tolerance of cultivated plants the use of compounds of the present invention enables to improve the management of harvest, time of harvest, quality and quantity of the harvest.

Imidazolines benzoheterocycles compounds may be used in the fir, as wettable powders, dispersible granules, granular forms, etc.

If herbicide-active compounds are water soluble, they can simply be dissolved in water and applied in the form of water jets. The above compounds can also be arranged in the form of emulsifiable concentrate and diluted with water immediately prior to use in the form of a spray. The composition of the emulsifiable concentrate can be obtained by dissolving about 5-25 wt. active compounds in about 65-90 wt. N-methyl-pyrrolidone, isophorone, butylcellosolve, acetate, etc., and dispersing therein about 5-10 wt. non-ionic surface-active agent such as alkylenedioxy alcohol.

Compositions of wettable powders can be obtained by grinding together about 20-45 wt. finely powdered carrier such as kaolin, bentonite, diatomaceous earth, attapulgite, etc., about 40-80 wt. herbicide-active compounds, and about 2-5 wt. non-ionic surface-active agent such as alkylenedioxy alcohol.

General granular products can be obtained by dissolving the active compound in the solvent Tel-clay such as attapulgite or kaolin,thus, to obtain about 3-20 wt. active compound and about 80-97 wt. media.

To facilitate further understanding of the present invention, the following examples are presented primarily for purposes of illustration, some additional details. The present invention is not limited by nothing but claims.

Reduction kg/ha denotes kilograms/hectare. Reduction NOE, 1H-NMR and IR denote the nuclear effect of Overhouse, proton nuclear magnetic resonance and infrared spectrum, respectively. The term Ehud denotes liquid chromatography high pressure. All parts are mass parts, unless stated otherwise.

Example 1. Getting dimethyl 4-acetamido-5-nitrophthalic /I/ and dimethyl 4-acetamido-3-nitrophthalic /II/.

< / BR>
Dimethyl 4-acetamidophenol /100,4 g, 0.400 mol) was added fuming nitric acid /90% 600 ml/ at a temperature of from 0 to 5oC. When the addition is finished /0.5 h, the mixture was stirred for 2.5 h at 0 to 10oC, connected with cold methylene chloride and shaken with crushed ice. The aqueous layer was separated and then extracted with methylene chloride. United organizations is concentrated under vacuum, to obtain a solid residue. The residue was subjected to recrystallization twice from methanol to obtain the product I from header example in the form of orange-brown needles, melting point 119-120oC. Initial mother liquor was concentrated under vacuum, and the residue was subjected to recrystallization several times from carbon tetrachloride to obtain compound II header example in the form of bright yellow needles, melting point 124-125oC. the Yield of compound I is equal to 38.3 g (32.9 per cent), and the yield of compound (II) is equal to 33.1 g (28,1%).

Example 2. Getting dimethyl 2-methyl-4,5-benzimidazolecarboxylate.

< / BR>
A mixture of dimethyl 4-acetamido-3-nitrophthalic (142,1 g to 0.480 mol) in methanol with 5% platinum on carbon (catalyst) was subjected to hydrogenation in hydrogenator Parra at room temperature. The reaction mixture was filtered through diatomaceous earth and concentrated under vacuum to obtain a solid residue. This solid was dispersible in glacial acetic acid and toluene and was heated with stirring at a temperature of deregulirovania for 4 h with azeotropic removal of water. The resulting hot reaction mixture was slowly added to easysector to receive the product from the header of the example as a white solid (71,6 g, 60,1%), melting point 97-103oC.

Example 3. Obtaining 2-methyl-4,5-benzimidazolecarbamic acid

< / BR>
A mixture of dimethyl 2-methyl-4,5-benzimidazolecarboxylate and 8 equivalents of a 10N solution of hydrate of sodium oxide was stirred 4 h at a temperature of 70oC, cooled and acidified with hydrochloric acid to obtain a product of header example in the form of cream-colored crystals, melting point 270oC (Razlog.).

Example 4. Getting 4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-2-methyl-4-benzimidazole carboxylic acid (I) and 5-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-2-methyl-4 - benzimidazolecarbamic acid /II/, 4:1-mixture.

< / BR>
A mixture of 2-methyl-4,5-benzimidazolecarboxylate /of 5.00 g, 22.7 mmol/ or acetic anhydride was stirred for 6 hours at a temperature of deregulirovania, cooled and concentrated under vacuum to obtain a residue. The residue was transferred in acetonitrile and treated a-methyl-valeramide /5,90 g of 45.3 mg/ DL. The resulting mixture was stirred 15 h at a temperature of deregulirovania, cooled and kept in overnight. Utverzhdennuyu the reaction mixture was transferred into a 5N solution of hydrate of sodium oxide, was heated up to those who trated HCl, to obtain a brown solid to precipitate which was removed by filtration. The brown solid was heated in methanol, filtered hot, and the filtrate was concentrated under vacuum to obtain the product from the header of the example in the ratio 4: 1 to I:II, respectively, in the form of a yellow powder (0,93 g, 13,0%), melting point 256oC (Razlog.).

Example 5. Getting dimethyl 1,2-dimethyl-4,5-benzimidazolecarboxylate

< / BR>
The sodium methylate (1.98 g, 36.6 mmol) was added to a solution of dimethyl 2-methyl-4,5-benzimidazolecarboxylate (7,44 g, 33.3 mmol) in methanol and tetrahydrofuran. After 5 min was added logmean (2,18 ml of 35.0 mmol) and the mixture was stirred for 24 h at room temperature. Added additional sodium methylate (1,80 g, 33.3 mmol) and jodean (2,07 ml, 33.3 mmol) and stirring continued for 15 hours, the Reaction mixture was concentrated under vacuum to get a residue, which was dispersible in dilute hydrochloric acid and treated with sodium bicarbonate to pH 8 and extracted with chloroform. The combined organic extracts were dried (magnesium sulfate) and concentrated under vacuum to get a residue, which was subjected to recrystallization iocchi melting 205-208oC.

Example 6. Obtaining 1,2-dimethyl-4,5-benzimidazole-dicarboxylic acid

< / BR>
A mixture of dimethyl 1,2-dimethyl-4,5-benzimidazolecarboxylate (1.70 g, of 6.49 mmol) and a 2N solution of hydrate of sodium oxide (25 ml, 12.5 mmol) was stirred 5 h at 100oC. the Mixture was cooled, acidified to pH 4 with hydrochloric acid and filtered to obtain the product of the header example in the form of a white powder (1,32 g, and 86.8%) melting point 305-308oC (Razlog.).

Example 7. Obtaining 1,2-dimethyl-4,5-benzimidazolecarbamate anhydride

< / BR>
A mixture of 1,2-dimethyl-4,5-benzimidazolecarbamic acid (1,00 g, 4,27 mmol) and acetic anhydride (10 ml) was stirred 4 h at the temperature of reflux distilled, was kept over night at room temperature and filtered to obtain the product of the header example in the form of yellow crystals (0,830 g, 89,8%), melting point 295oC (Razlog.).

Example 8. Getting 4-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl]-1,2 - dimethyl-6-benzodiazepinovoj acid /I/, 5-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl] -1,2-dimethyl-4 - benzimidazolecarbamic acid /II/, 4: 1-mixture

< / BR>
A mixture of 1,2-dimethyl-4,5-benzimidazolecarbamate anhydride (0,830 g of 3.85 mmol), and-the overnight and filtered, to get the product from the header of the example as a white solid (1.24 g, 93,2% ), melting point 246-248oC, which was identified through 1H-NMR as 4:1-mixture of compound I and compound II, respectively.

Example 9. Getting 4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-1,2 - dimethyl-5-benzimidazolecarbamic acid

< / BR>
A solution of 4-[/1-Carbarnoyl-1,2-dimethylpropyl/-carbarnoyl] -1,2 - dimethyl-6-benzimidazolecarbamic acid (5,70 g, 16.5 mmol) and 10N solution of hydrate of sodium oxide (9,88 ml, 98,8 mmol) was stirred 3 hours at the temperature of reflux distilled, cooled to 0oC and acidified to pH 4 with hydrochloric acid and filtered. The filter cake was dried to obtain a product of header example in the form of a white solid (4.11 g, 75.8 per cent), the melting point 280-285oC (decomposition).

Example 10. 9-isopropyl-2,3,9-trimethylimidazo [1',2':1,2] pyrrolo [3,4-e] benzimidazole-6,8/3H,9H/-Dion

< / BR>
A mixture of 4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-1,2 - dimethyl-5-benzimidazolecarbamic acid (0,942 g, 2,87 mmol), dicyclohexylcarbodiimide (0,590 g, 2,87 mmol) and tetrahydrofuran (THF) was stirred for 3 h at the temperature of reflux distilled, cooled and koncentrira header example in the form of a white powder (0,210 g, 23,6%), melting point 258-263oC.

Example 11. Obtain methyl 4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/- 1,2-dimethyl-5-benzimidazolecarboxylate

< / BR>
The solution diazomethane simple ether was added dropwise to a solution of 4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-1,2 - dimethyl-5-benzimidazolecarbamic acid (2.50 g, to 7.61 mmol) in methanol until then, until the yellow color. The reaction mixture was neutralized with acetic acid and concentrated under vacuum. After preparative ghvd (silica gel, ethyl acetate eluent) received the product header example in the form of off-white crystals (0,750 g, 28.9 percent), the temperature of the melting point of 240-242oC.

Example 12. Getting dimethyl 1-benzyl-2-methyl-4,5-benzimidazolecarboxylate

< / BR>
Sodium hydride (0,750 g, 80% oil dispersion, 25,0 mmol) was added in portions to a solution of dimethyl 2-methyl-4,5-benzimidazolecarboxylate (6,07 g, 24.6 mmol) in dry dimethylformamide at 0oC under stirring. After the evolution of hydrogen ceases, benzylbromide (2,93 ml, 24.6 mmol) was added to the reaction mixture and stirring was continued for 16 hours the Reaction mixture was concentrated under vacuum and the resulting OS the organic phases were combined, was dried and concentrated under vacuum to obtain a solid residue. After recrystallization solids from ethyl acetate received the product header example in the form of not quite white powder (3,81 g 45,0%), melting point 192-195 (in Russian)oC.

Example 13. Obtain 1-benzyl-2-methyl-4,5-benzimidazolecarbamic acid

< / BR>
A mixture of dimethyl 1-benzyl-2-methyl-4,5-benzimidazolecarboxylate (5.50 g, 16.2 mmol), methanol, 10N solution of hydrate of sodium oxide (13 ml, 130 mmol) and water was stirred for 4 h at 70oC, cooled, acidified to pH 4 with hydrochloric acid and filtered to obtain the product of the header example in the form of not-quite-white solid (4.94 g, 98.4 per cent), the melting point 224-226oC.

Example 14. Obtain 1-benzyl-2-methyl-4,5-benzimidazolecarbamate anhydride

< / BR>
A mixture of 1-benzyl-2-methyl-4,5-benzimidazolecarbamic acid (4,40 g of 14.2 mmol) and acetic anhydride was stirred 5 h at a temperature of deregulirovania, cooled to 0oC and filtered to obtain the product of the header example in the form of a pale yellow solid (of 3.78 g, to 91.1%), which was identified using 1H-NMR spectroscopy.

Example 15. Paucinervis-1,2-dimethylpropyl/-carbarnoyl]-2-methyl-4-benzimidazole - Borovoy acid (II), 4:1-mixture

< / BR>
A mixture of 1-benzyl-2-methyl-4,5-benzimidazolecarbamate anhydride /3,70 g, 12.7 mmol/ as-methylvaleramide /1.70 g, 13,0 mmol) and acetonitrile was stirred for 6 hours at a temperature of deregulirovania, cooled to 0oC and filtered to obtain the product from the header of the example, 4:1-mixture of compound I and compound II, respectively, in the form of not quite white powder (4,08 g, 76,1% ), melting point 194-196oC. the product was identified through 1H-NMR spectral analysis.

Example 16. Obtain 1-benzyl-4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-2-methyl-5 - benzimidazolecarbamic acid.

< / BR>
A mixture of 1-benzyl-4-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl] -2-methyl-5 - benzimidazolecarbamic acid (3:58 g of 8.47 mmol), 10 N solution of hydrate of sodium oxide (5,06 ml, 50.8 mmol) and water was stirred for 4 hours at a temperature of deregulirovania, cooled, acidified to pH 4 hydrochloric acid and filtered. The filter cake was subjected to recrystallization from acetonitrile, to obtain the product of the header example in the form of not quite white powder (1.06 g, 31,0%), melting point 198-208oC (decomposition).

Example 17. Obtain methyl 1-benzyl-4-/4-idrostop ether was added to a suspension of 1-benzyl-4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-2 - methyl-5-benzimidazolecarbamic acid (1,15 g, 2,84 mmol) in methanol until then, until the yellow color. The reaction was stirred 5 min, stopped by addition of 2 drops of acetic acid and concentrated under vacuum. The resulting residue was subjected to purification using ghvd (silica gel, ethyl acetate eluent) to obtain the product of the header example in the form of a white powder (to 0.480 g, 40.3 per cent), the melting point 194-196oC.

Example 18. Getting dimethyl 1-ethyl-2-methyl-4,5-benzimidazolecarboxylate

< / BR>
Sodium hydride (1,38 g, 46,0 mmol, 80% oil dispersion) was added in portions to a solution of dimethyl 1-benzyl-2-methyl-4,5-benzimidazolecarboxylate (10,9 g that 43.8 mmol) in dry dimethylformamide at 0oC. After the evolution of hydrogen ceases, ethyl iodide (3,68 ml of 46.1 mmol) was added. The reaction mixture was stirred at room temperature overnight, treated with ethyl acetate and filtered. The filtrate was concentrated under vacuum; the resulting residue was subjected to recrystallization from a mixture of 50% ethyl acetate:hexanol to get the product from the header example in the form of a bright yellow powder (3,84 g, 31.7 percent), melting point 126,5-128oC.

Example 19. Obtain 1-ethyl-2-methyl-4,5-benimeli), methanol and 5N solution of hydrate of sodium oxide (30 ml, 150 mmol) was stirred for 4 h at 100oC, cooled, acidified with hydrochloric acid and filtered to obtain the product of the header example in the form of a lemon-yellow powder (4,07 g, 85,5%), which was identified using 1H-NMR spectral analysis.

Example 20. Obtain 1-ethyl-2-methyl-4,5-benzimidazolecarbamate anhydride

< / BR>
A mixture of 1-ethyl-2-methyl-4,5-benzimidazolecarbamic acid (4,00 g, 16,1 mmol) and acetic anhydride (50 ml) was stirred 5 h at the temperature of reflux distilled, cooled and filtered. The filter cake was washed with a simple ether and dried to obtain the product of the header example in the form of Golden plates (3,37 g, 90,8%), which was identified using 1H-NMR spectral analysis.

Example 21. Getting 4-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl]-1-ethyl-2-methyl-5 - benzimidazolecarbamic acid (I) and 5-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl] -1-ethyl-2-methyl-4 - benzimidazolecarbamic acid (II), 4:1 mixture of

< / BR>
A mixture of 1-ethyl-2-methyl-4,5-benzimidazolecarbamate anhydride (3,30 g of 14.3 mmol), and methylvaleramide (1.90 g, 14.5 mmol) and acetonitrile was stirred 2 h at the temperature of reflux distilled in t the vacuum up to 50% of the original volume and filtered, to get the product from the header example in the form of a 4:1 mixture of compound I and compound II bright yellow (powder) (4.59 g, 88,8%), melting point 240-243oC.

Example 22. Obtain 1-ethyl-4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/- 2-methyl-5-benzimidazolecarbamic acid

< / BR>
A mixture of 4-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl] -1-ethyl - 2-methyl-5-benzimidazolecarbamic acid (4.09 g, to 11.4 mmol), 10 N solution of hydrate of sodium oxide (6.8 ml, to 68.0 mmol) and water was stirred for 2 h at the temperature of reflux distilled, cooled, acidified to pH 4 with hydrochloric acid and filtered. The filter cake was subjected to recrystallization from acetonitrile, to obtain the product of the header example in the form of a white powder (1.10 g, 28.2 per cent), the melting point 250-256oC (Razlog).

Example 23. Obtain methyl 1-ethyl-4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin - 2-yl/-2-methyl-5-benzimidazolecarboxylate

< / BR>
The solution diazomethane simple ether was added dropwise to a mixture of the original carboxylic acid (2.10 g, 6,13 mmol) in methanol until then, until the yellow color is not stabilized. After 5 min the reaction was stopped with acetic acid and concentrated under vacuum. Received in rezultatele as not quite white powder (1,03 g, 47,2%), melting point 189-191oC.

Example 24. Getting dimethyl 2-methyl-5,6-benzimidazolecarboxylate

< / BR>
A mixture of dimethyl 4-acetamido-5-nitrophthalic, methanol and 5% platinum on carbon was subjected to hydrogenation in hydrogenator Parra. The reaction mixture was filtered through diatomaceous earth and the filtrate concentrated under vacuum. Thus obtained crude diamine (intermediate compound, 48,09 g, 0,180 mmol) was mixed with para-toluene/mono/acid (51,4 g, 0,270 mol) and toluene (400 ml) and was stirred for 2 h at the temperature of reflux distilled under azeotropic removal of water, cooled and concentrated under vacuum. The resulting residue was subjected to recrystallization from methanol, to obtain para-toluene sulphonate salt of the product from the header of the example. This salt was dissolved in hot water, made alkaline with sodium bicarbonate and was extracted with methylene chloride. The United extracts were washed with brine, dried (magnesium sulfate) and concentrated under vacuum to obtain a red solid. After recrystallization of a portion of a red solid was obtained the product from the header of the example as white crystals, the temperature of the point of the Sabbath. < / BR>
The sodium methylate (1,96 g of 36.3 mmol) was added to a solution of dimethyl 2-methyl-5,6-benzimidazolecarboxylate (8,50 g, 34,2 mmol) in methanol. The reaction mixture was stirred 0.5 h at room temperature, was treated with iodomethane (2,15 ml, 34.5 mmol), stirred overnight, acidified to pH 6 with acetic acid, was treated with sodium bicarbonate to pH 8 and extracted with chloroform. The extracts were combined, dried (magnesium sulfate) and concentrated under vacuum to obtain the product of the header example in the form of a pink solid (6.25 g, 63.7 per cent). A small portion was subjected to recrystallization from ethyl acetate to obtain the product of the header example in the form of pink crystals, melting point 147-148oC.

Example 26. Obtaining 1,2-dimethyl-5,6-benzimidazolecarbamic acid

< / BR>
A mixture of dimethyl 1,2-dimethyl-5,6-benzimidazolecarboxylate (2,80 g of 10.7 mmol), potassium hydroxide (1,49 g, to 26.7 mmol), water and methanol was stirred at room temperature for 16 h, and then concentrated under vacuum. The resulting residue was transferred into a minimum amount of water, cooled, acidified to pH 3 with hydrochloric acid and filtered to obtain the product of the title etc is the significance of 1,2-dimethyl-5,6-benzimidazolecarbamate anhydride

< / BR>
A mixture of 1,2-dimethyl-5,6-benzimidazolecarbamic acid (1.25 g, of 5.34 mmol) and acetic anhydride was stirred for 2 h at the temperature of reflux distilled, cooled to 5oC and filtered. The filter cake was dried to obtain a product of header example in the form of brown needles (1.04 g, 90,1%), melting point 310-315oC).

Example 28. Obtain 6-[/1-carbarnoyl-1,2-dimethyl-propyl/-carbarnoyl]-1,2 - dimethyl-5-benzimidazolecarbamic acid (I) and 5-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl]-1,2-dimethyl-6 - benzimidazole carboxylic acid (II)

< / BR>
A mixture of 1,2-dimethyl-5,6-benzimidazolecarbamate anhydride (0,500 g, 2,31 mmol), and methylvaleramide (0,300 g, 2,31 mmol) and acetonitrile was stirred for 3 h at the temperature of reflux distilled, cooled and filtered. As a result of recrystallization of the filter cakes of methanol was received compound I in the form of a white powder (0,230 g, 28,8), melting point 169-171oC. the mother liquor was concentrated under vacuum to a yellow solid, which was subjected to recrystallization from methanol, to obtain a connection from the header of example II in the form of a white foam (0,240 g 30,0%), melting point 145-150oC.

Example 29. the notes

< / BR>
A mixture of 6-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl] -1,2-dimethyl-5 - benzimidazolecarbamic acid (0,330 g, 0,910 mmol) and 2M solution of hydrate of sodium oxide (3.0 ml, 6.0 mmol) was stirred for 2.5 hours at the temperature of reflux distilled, cooled, acidified to pH 3 with hydrochloric acid and filtered. The filter cake was subjected to recrystallization from ethanol to obtain the product from the header of the example as a white solid (0,120 g, 31.5%) and the melting point 256-258oC.

Example 30. Obtain methyl 5-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-1,2-dimethyl - benzimidazolecarboxylate

< / BR>
A mixture of the original diamine (0,510 g of 1.47 mmol) and 2M solution of hydrate of sodium oxide (5.0 ml, 10.0 mmol) was stirred for 2.5 h at the temperature of reflux distilled, cooled, acidified to pH 3 with hydrochloric acid and filtered. The filtrate was concentrated under vacuum to obtain a white solid, which was dissolved in methanol and treated with a solution of diazomethane simple ether until then, until the yellow color. The reaction was quickly stopped with acetic acid and concentrated under vacuum. The resulting residue was subjected to chromatography (silicogermanate the melting point 138-140oC.

Example 31.

< / BR>
A suspension of sodium hydride (14.6 g, 0,365 mol, 60% oil dispersion) in dry benzene at 5-10oC was treated 1,5,6,7-tetrahydro-1,3-dimethyl-4H-indazol-4-one (30.0 g, 0,183 mol). The reaction mixture was treated dropwise ethyl carbonate (45,0 ml, 0,365 mol) and ethanol (1.0 ml) under cooling, stirred for 11 h at the temperature of reflux distilled, cooled to room temperature and treated with acetic acid (24,1 g, 0.400 mol) and water. The phases were separated, the organic phase was removed, and the aqueous phase was extracted with simple ether. The organic phases were combined, washed with water, dried (sodium sulfate) and concentrated under vacuum. The resulting residue was twice replaced by toluene, subjected to recrystallization from (2: 1) methylene chloride/heptane, and the second time - out of 50% tetrahydrofuran/heptane to obtain the product of the header example (27,6 g, 63.9 per cent), the melting point of 76.5-79oC.

Example 32. Obtain ethyl 4-cyano-4,5,6,7-tetrahydro-1,3-dimethyl-4-/trimethyl - siloxy/-1H-indazol-5-carboxylate

< / BR>
A solution of ethyl 4,5,6,7-tetrahydro-1,3-dimethyl-4-oxo-1H-indazol-5-carboxylate (41,0 g, 0,174 mol) in benzene was stirred at the temperature of reflux distilled azeotropic del mol), was stirred 15 min at 65oC, was treated with zinc iodide (2.00 g, 0,00688 mol), was stirred 6 h at 65oC, was kept over night at room temperature and concentrated under vacuum to obtain the product of the header example in the form of oil, which was identified by IR and mass spectroscopy.

Example 33. Obtain ethyl 4-cyano-6,7-dihydro-1,3-dimethyl-1H-indazol-5-carboxylate

< / BR>
A solution of ethyl 4-cyano-4,5,6,7-tetrahydro-1,3-dimethyl-4-/three - methylcellulose/-1H-indazol-5-carboxylate (28,1 g, 0,119 mol) in pyridine was mixed with phosphorus oxychloride (43,0 ml, 0,461 mol), was stirred for 5 hours at a temperature of reflux distilled and concentrated under vacuum. The resulting black residue was diluted with ethyl acetate and water, and treated with sodium bicarbonate to pH 6. The phases were separated, the organic phase is left, and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with aqueous sodium bicarbonate solution and water, dried (magnesium sulfate) and concentrated under vacuum to get the black residue. The residue is triturated with ethyl acetate to obtain the product of the header example in the form of a reddish-brown solid (15.5 g, 52.9 per cent), which identify the 5-carboxylate

< / BR>
A mixture of ethyl 4-cyano-6,7-dihydro-1,3-dimethyl-1H-indazol-5 - carboxylate (13.5 g, 55,0 mmol), ortho-chloranil (16.3 g, 66,0 mmol) and dry benzene was stirred for 1.5 h at a temperature of deregulirovania, cooled and filtered. The filtrate was concentrated under vacuum, filtered through two bags of neutral alumina and evaporated until dry, to obtain yellow solid. As a result of recrystallization from ethyl acetate received the product header example (6,33 g, 47.2 percent), melting point 170-175,5oC.

Example 35. Obtain 1,3-dimethyl-1H-indazol-4,5-dicarboxylic acid

< / BR>
A mixture of ethyl 4-cyano-1,3-dimethyl-1H-indazol-5-carboxylate (7,03 g, 28.7 mmol), concentrated Hydrobromic acid (35 ml) and acetic acid (35 ml) was stirred for 2 hours at a temperature of deregulirovania, cooled, diluted with water (200 ml) and stirred 2 h After filtering the reaction mixture obtained product header example in the form of a pale blue solid (6,57 g, 97.8 per cent ), the melting point 228,5-reach 232.5oC.

Example 36. Obtain 1,3-dimethyl-1H-indazol-4,5-dicarboxylic anhydride

< / BR>
A mixture of 1,3-dimethyl-1H-indazol-4,5-dicarboxylic acid (6,30 g, travali. The filter cake was air dried to obtain the product of the header example in the form of needles color Chartreuse (4,80 g, 82.5 per cent), the temperature of the melting point of 214-215,5oC.

Example 37. Getting 4-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl]1,3-dimethyl - 1H-indazol-5-carboxylic acid

< / BR>
A mixture of 1,3-dimethyl-1H-indazol-4,5-dicarboxylic anhydride (1.60 g, 7.40 mmol), triethylamine/1,12 ml, 8,10 mmol), and-methyluronamide (1.06 g, 8,14 mmol), dimethoxyethane and dimethylformamide was stirred for 16 h at room temperature and concentrated under vacuum. The resulting residue was diluted with water and filtered to obtain the product of the header example in the form of a white solid. After acidification of the filtrate to pH received additional product, which was identified using 1H-NMR, IR and mass spectroscopy. The total yield of 2.00 g (78,1%).

Example 38. Obtain methyl 4-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl]- 1,3-dimethyl-1H-indazol-5-carboxylate

< / BR>
A solution of 4-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl] 1,3 - dimethyl-1H-indazol-5-carboxylic acid (determined as 0.720 g, 2,07 mmol) in dry dimethylformamide was treated with a sufficient amount of diazomethane simple ether to obtain a constant ultracomm. The resulting residue was replaced 2 times with xylene, was subjected to recrystallization from 50% aqueous methanol to obtain the product of the header example in the form of a white solid, melting point 221-222oC.

Example 39. Obtain methyl 4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-1,3-dimethyl - 1H-indazol-5-carboxylate

< / BR>
A mixture of methyl 4-[/1-carbarnoyl-1,2-dimethylpropyl/carbarnoyl]- 1,3-dimethyl-1H-indazol-5-carboxylate (0,600 g, 1,67 mmol), pentachloride phosphorus (1.04 g, 5.00 mmol) and dry toluene (7.0 ml) was stirred for 3.5 h at 90oC, cooled and filtered. The filter cake was washed with toluene, to prepare a slurry in water, treated with sodium bicarbonate (0,370 g, 4.40 mmol) to pH 8.5 and was filtered to obtain the product from the header of the example as a white solid (0,490 g, 85.7 percent), melting point 130-150oC.

Example 40. Getting 4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-1,3 - dimethyl-1H-indazol-5-carboxylic acid

< / BR>
A mixture of methyl 4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/- 1,3-dimethyl-1H-indazol-5-carboxylate (0,310 g, 0,905 mmol), 2N solution of hydrate of sodium oxide (of 0.91 ml, 1.82 mmol) and tetrahydrofuran (11 ml) was stirred tip is ovali chloroform. The organic extracts were dried (sodium sulfate) and concentrated under vacuum to get a residue, which was subjected to recrystallization from acetonitrile, to obtain the product from the header of the example as a white solid (0,160 g, 53.2 per cent), the melting point 156,5-166oC.

Example 41. Getting 1-methylpyrrole-3-carboxaldehyde

< / BR>
Monomethylamine (20 g, of 0.64 mol) was added through the condenser with dry ice in a mixed solution of 2,5-dimethoxy-3-tetrahydrobenzaldehyde of 48.1 g, 0,300 mol) in glacial acetic acid (500 ml) at 10oC. the dry ice Condenser was replaced with a water condenser and the reaction mixture was stirred 2 h at 110oC, cooled to room temperature and subjected to distillation at 25-30oC/4,0 mm RT. Art. to remove acetic acid. The residue was diluted with ice water, washed with simple ether, cooled, treated with hydrate of sodium oxide to pH 7 and extracted with methylene chloride. The organic extracts were combined, dried (magnesium sulfate) and concentrated under vacuum to obtain products from header example in the form of a red liquid (11,0 g, 33.6 per cent), which was identified using 1H-NMR spectroscopy.

Example 42. The floor is sparse) in dry tetrahydrofuran under nitrogen atmosphere was added bromide methyltriphenylphosphonium (51.8 g, 0,145 mol). The mixture was stirred 1 h at a temperature of deregulirovania, cooled to 45oC and treated dropwise with a solution of 1-methylpyrrole-carboxaldehyde (15,8 g, 0,145 mol) in tetrahydrofuran. The resulting mixture was stirred for 6 days at room temperature and filtered through neutral alumina with petroleum ether, as an additional eluate. The filtrate was concentrated under vacuum to a yellow-white semi-solid substance, which was diluted with petroleum ether and again filtered through neutral alumina. The colorless filtrate was concentrated under vacuum to obtain the product of the header example in the form of a pale yellow oil (10.1 g, 65.2 percent), which was identified using 1H-NMR spectroscopy.

Example 43. Getting hexahydro-a-isopropyl-a,1-dimethyl-6,8 - dioxobenzo[2,1-b:3,4-c']dipyrrole-7/1H/-acetonitrile

< / BR>
A mixture of 1-methyl-3-vinylpyrrole (9,50 g 0,089 mol), a-isopropyl-a-methyl-2,5-dioxo-3-pyrrolin-1-acetonitrile (17.0 g, 0,089 mol) and chloroform was stirred over night at room temperature and concentrated under vacuum to an amber oil residue. This residue was subjected to evaporative chromatography (silica gel, elution gradient: 50% hexane, 8,8%), which was identified using 1H-NMR spectroscopy.

Example 44 Getting 6,8-dihydro-a-isopropyl-a, 1-dimethyl-6,8 - dioxobenzo[2,1-b:3,4-c']dipyrrole-7/1H/-acetonitrile

< / BR>
A mixture of hexahydro-2-isopropyl-a,1-dimethyl-6,8 - dioxobenzo[2,1-b:3,4-c'] dipyrrole-7/1H/-acetonitrile (of 9.30 g, 30.0 mmol), manganese dioxide (7,00 g, 80,5 mmol) and chlorobenzene was stirred at a temperature of deregulirovania during the night, was treated with an additional amount of manganese dioxide (3.50 g, with 40.2 mmol) and was heated for another 16 hours to a temperature of deregulirovania. Added a third portion of manganese dioxide (3.50 g, with 40.2 mmol) and the reaction mixture was stirred 3 days at a temperature of deregulirovania, cooled to 25oC and concentrated under vacuum to get the black residue. The residue was subjected to evaporative chromatography (silica gel, 50% simple ether:hexane) to obtain the product from the header of the example as a yellow solid (4,30 g, 48.5 percent), melting point 134-138oC.

Example 45. Obtain 6,8-dihydro-a-isopropyl-a,1-dimethyl-6,8 - dioxobenzo[2,1-b:3,4-c']dipyrrole-7/1H/-ndimethylacetamide

< / BR>
A solution of 6,8-dihydro-to-isopropyl-a, 1-dimethyl-6,8 - dioxobenzo[2,1-b: 3,4-c'] dipyrrole-7/1H/-acetonitrile (5.30 g, 18.0 mmol) in methylenediamine. The ice bath was removed and the reaction mixture was stirred over night at ambient temperature, poured on crushed ice, diluted with methylene chloride, and treated with 50% solution of hydrate of sodium oxide when cooled ice bath to pH 3-4 and shared. The aqueous layer was extracted with methylene chloride. The combined organic layers were dried (magnesium sulfate) and concentrated under vacuum to obtain a residue in the form of an orange foam, which was subjected to recrystallization from methylene chloride to obtain a product of header example in the form of yellow crystals (1.30 grams, 23,2%), melting point 184-189oC.

Example 46. Getting 8-isopropyl-1,8-dimethyl-1H-imidazo[1',2':1,2]pyrrolo[3,4-g]indole-6,9- -dione and 8-isopropyl-1,8-dimethyl-1H-imidazo[2',1':5,1] pyrrolo[3,4-g]-indole - 7,10-dione (1:1 mixture)

< / BR>
Sodium hydride (0,240 g, 6,00 mmol, 60% oil dispersion) portions was added to a mixture of 6,8-dihydro-a-isopropyl-a-1 - dimethyl-6,8-dioxobenzo[2,1-b: 3,4-c']dipyrrole-7/1H/-ndimethylacetamide (to 0.900 g, 2,87 mmol) and dry toluene at a temperature of deregulirovania. After 1 h at the temperature of deregulirovania the mixture was cooled to room temperature and filtered through diatomaceous earth. The filtrate was concentrated under vacuum to receive assistance 1H-Amspecblog analysis.

Example 47. Obtaining methyl [7-/4-isopropyl-4-methyl-6-oxo-2-imidazolin-2-yl/-1 - methyl] indole-6-carboxylate and methyl [6-/4-isopropyl-4 - metal-5-oxo-2-imidazolin-2-yl/-1-methyl]indole-7-carboxylate (1:1-mixture)

< / BR>
A catalytic amount of sodium hydride (60% oil dispersion) was added to a solution of 1:1-mixture of 8-isopropyl-1,8-dimethyln - imidazo[1',2':1,2] pyrrolo[3,4-g] indole-6,9-dione and 8-isopropyl-1,8-dimethyl-1H-imidazo[2', 1': 5,1] pyrrolo[3,4-g] -indole -7,10 Dion (to 0.900 g, 3.00 mmol) in methanol at room temperature to pH 10. After 5 days was added sodium hydride to pH 10-11 and the reaction mixture was heated using a steam bath for 1 H. After cooling to room temperature was added acetic acid to pH 6 and the mixture was concentrated under vacuum. The residue was diluted with methylene chloride and water; the organic layer was dried (magnesium sulfate) and concentrated under vacuum to obtain the product from the header of the example as a yellow foam (0,350 g, 37.7 per cent). Identification was carried out using 1H-NMR spectral analysis.

Example 48. Getting 7-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-1 - methylindol-6-carboxylic acid and 6-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-1-methylindol-7 - carboxylic acid (1:1-mixture)

< / BR>
I-I-a mixture of methyl[7-/4-is Zolin-2-yl/-1-methyl]indole - 7-carboxylate /0,350 g, 1.07 mmol/ methanol and N 1,93 solution of hydrate of sodium oxide (0,60 ml of 1.16 mmol) was stirred over night at room temperature. The reaction mixture was concentrated under vacuum and the residue was diluted with water, treated with concentrated hydrochloric acid to pH 3 and filtered to obtain the product of the header example in the form of a bright yellow solid (0,140 g), melting point 122-140oC.

Example 49. Obtain 1-methyl-2-vinylpyrrole

< / BR>
Bromide methyltriphenylphosphonium (35,7 g, 0,100 mol) was added to a slurry of sodium hydride (4,80 g, 0,120 mol, 60% oil dispersion) in dry tetrahydrofuran at 10oC in nitrogen atmosphere. The mixture was stirred at a temperature of deregulirovania 1 h, cooled to 35oC was treated dropwise with a solution of 1-methylpyrrole-2-carboxaldehyde (10,9 g, 0,100 mol) in tetrahydrofuran, stirred for 3 days at ambient temperature, 2 h under delegirovano and 16 h at room temperature. The reaction mixture was filtered through neutral alumina with petroleum ether. Clear yellow filtrate was concentrated under vacuum to obtain a bright yellow semi-solid substance that is transported in petroleum ether and filtered through Laperouse under vacuum, to get the product from the header of the example as colorless transparent oil /7,80 g, 72,5%/, which was identified using 1H-NMR spectroscopy.

Example 50. Obtaining 3,3 a, 4,5,6,8 in-hexahydro-a-isopropyl-a, 6-dimethyl,3 dioxobenzo/1,2-b:3,4-c'/dipyrrole-2/1H/-acetonitrile

< / BR>
A mixture of 1-methyl-2-vinylpyrrole (3,90 g, 36,0 mmol), a-isopropyl-a-methyl-2,5-dioxo-3-pyrrolin-1-acetonitrile (7,00 g, 36,0 mmol) and chloroform was stirred over night at room temperature and concentrated under vacuum. The resulting residue was subjected to evaporative chromatography (silica gel, 50% simple ether: hexane - eluent) to obtain the product of the header example in the form of a clear yellow glass (63.5 g, 58.8 per cent).

Example 51. Getting 3,6-dihydro-a-isopropyl-a,6-dimethyl-1,3 - dioxobenzo[1,2-b:3,4-c']dipyrrole-2/1H/-acetonitrile

< / BR>
Activated manganese dioxide (27,0 g, 0,310 mol) was added to a solution of 3,3 a, 4,5,6,8 in-hexahydro-a-isopropyl-a, 6-dimethyl-1,3 - dioxobenzo[1,2--b: 3,4-c']dipyrrole-2/1H/-acetonitrile (51,3 g, 0,167 mol) in chlorobenzene. The reaction mixture was stirred overnight at a temperature of deregulirovania, cooled and filtered twice through diatomaceous earth with methylene chloride. The filtrate content, then a mixture of hexanol: methylene chloride, to obtain yellow solid (5.50 g, 11.6 percent ). As a result of recrystallization of hexanol: methylene chloride has received the product from the header of example, the melting point 123-128oC.

Example 52. Getting 3,6-dihydro-a-isopropyl-a,6-dimethyl-1,3 - dioxobenzo[1,2-b:3,4-c']dipyrrole-2/1H/-ndimethylacetamide

< / BR>
Concentrated sulfuric acid (5.50 ml) was added slowly into a solution of 3,6-dihydro-a-isopropyl-a, 6-dimethyl-1,3 - dioxobenzo[1,2-b: 3,4-c'] dipyrrole-2/1H/-acetonitrile (5.50 g, 19.0 mmol) in methylene chloride at 10oC. was Added crushed ice. The mixture was stirred 24 h at ambient temperature and was poured into crushed ice, and treated with 6N solution of hydrate of sodium oxide to pH 2 and extracted with methylene chloride. The organic layer was separated, dried (magnesium sulfate) and concentrated under vacuum to obtain a residue in the form of an orange foam. After evaporation chromatography (silica gel, simple ether, then ethyl acetate eluent) received the product from the header of the example as a yellow foam (1,53 g, 25.7 per cent), the melting point 159-168oC.

Example 53. Getting 8-isopropyl-3,8-dimethyl-1H - imidazo[1', 2':1,2] pyrrolo[3,4-e] indole-6,9-dione and 8-isopropyl-3,8-dimethyl-1H-Im1,2-b; 3,4-c']dipyrrole-2/1H/-ndimethylacetamide (2,60 g, 8,30 mol) portions was added to a suspension of sodium hydride (0.800 to g, of 16.6 mol, 50% oil dispersion) in toluene at a temperature of deregulirovania in nitrogen atmosphere. After stirring for 20 hours at a temperature of deregulirovania the mixture was filtered hot through diatomaceous earth, the yellow filtrate was concentrated under vacuum to a dark yellow oily residue, which was rubbed with simple ether to obtain the product from the header of the example as a yellow solid (1.60 g, 65%), which was identified using 1H-NMR spectroscopy.

Example 54. Obtaining methyl [5-/4-isopropyl-4-methyl-5-oxo-2 - imidazolin-2-yl/-1-methyl] indole-4-carboxylate (I) and methyl [4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-1-methyl]indole - 5-carboxylate (II)

< / BR>
A catalytic amount of sodium hydride (60% oil dispersion) was added to a solution of 1:1-mixture of 8-isopropyl-3,8-dimethyl-1H - imidazo[1',2':1,2] pyrrolo-[3,4-e] indole-6,9-dione and 8-isopropyl-3,8-dimethyl-1H-imidazo[2',1': 5,1] pyrrolo[3,4-e] indole-7,1 - 0-dione (1,00 g, 3,39 mmol) in methanol to pH 10. The reaction mixture was stirred for 1 h at room temperature, was treated with glacial acetic acid /2 drops/ and then concentrated under vacuum. The obtained magnesium) and concentrated under vacuum, to get an orange foam, which was subjected to evaporative chromatography (silica gel) to obtain 3 fractions, which were in the order of decreasing Rf:

1. Compound I from the header of example, a pale yellow solid (0,100 g);

2. The mixture of compounds I and II of the header example (0,60 g);

3. Compound II from the header of example, a pale yellow solid (0,080 g).

These fractions were identified using 1H-NMR spectroscopy.

Example 55. Getting 5-/4-isopropyl-4-methyl-5-oxo-2 - imidazolin-2-yl/-1-methylindol-4-carboxylic acid and 4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-1-methylindol-5 - carboxylic acid (1:1-mixture)

< / BR>
A mixture of 1.93 N solution of hydrate of sodium oxide (0,70 ml of 1.34 mmol), a 1:1 mixture of methyl[5-/4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl/-1 - methyl] indole-4-carboxylate and methyl 4-/4-isopropyl-4-methyl-5-oxo-2 - imidazolin-2-yl/-1-methyl/indole-5-carboxylate (0.400 g, 1,22 mmol) and methanol was stirred 4 days at room temperature and concentrated under vacuum. The resulting residue was diluted with water, cooled, acidified to pH 3 with concentrated hydrochloric acid and was extracted with ethyl acetate. The organic extracts were dried (magnesium sulfate) is (0,160 g, 41,9% ), melting point 266-280oC, which was identified through 1H-NMR analysis.

Example 56. Getting dimethyl 1H-benzotriazol-4,5-in primary forms

Mix a solution of methyl 3,4-diaminopimelate (2.24 g, 10 mmol) in acetic acid and methylene chloride was treated in one portion of ice solution isoamylamine (1.6 ml) in 1 ml of methylene chloride at 5oC. the Cooling bath was removed and the reaction mixture was allowed to heat up as a result of ectothermy 40oC, then heated up to 80oC for 30 min, cooled and concentrated under vacuum to obtain a brown oil. This residue was subjected to chromatography using alumina E and 2-5% methanol in chloroform as eluent to obtain the product of the header example in the form of a solid color of buff leather (0.73 g, 31% yield), melting point 147-150oC.

Example 57. Getting dimethyl 1-methyl-1H-benzotriazol-4,5 - in primary forms

< / BR>
Mix a solution of dimethyl 1H-benzotriazol-4,5-in primary forms (10.1 g, 43 mmol) in dimethylformamide was treated with a portion of the cooling sodium hydride. When gas evolution ceased, the reaction mixture was treated according drops diluted with a mixture of chloroform and water. The layers were separated, the organic layer was washed with brine, dried over magnesium sulfate and concentrated under vacuum to obtain a residue. The residue was subjected to chromatography using silica gel, 35% ethyl acetate in hexano to get the product from the header example in the form of a white solid substance and 3.15 g, melting point 146-147oC. the Structure was determined by NMR, AEO experiments.

Example 58. Getting 4-/4-isopropyl-4-methyl-5-oxo-2-imidazolin - 2-yl/-1-methyl-1H-benzotriazol-5-carboxylic acid

< / BR>
A mixture of dimethyl 1-methyl-1H-benzotriazol-4,5-in primary forms (0.73 g, 2.9 mmol) and a-methylvaleramide (0.40 g, 3.1 mmol) in toluene was treated with portions tration.-the butyl potassium (0.68 g, 6.1 mmol) for 30 minutes, heated to a temperature of deregulirovania for 5 hours, allowed to cool to room temperature for 26 hours, and treated with 5 ml of a 2N solution of hydrate of sodium oxide and stirred for 1 hour. The phases were separated and the organic phase was extracted with water. Prominent phases were combined, acidified to pH 3 with concentrated HCl, concentrated under vacuum to 1/2 the original volume, cooled to 5-10oC and filtered to obtain 3:2-mixture of the product isC.

Example 59. Herbicide evaluation of the test compounds to the emergence and used plant species are presented in table. 1, 2, respectively.

Herbicide activity to the emergence of imidazolines benzoheterocycles compounds that are the subject of the present invention was confirmed by the following tests, in accordance with which the seeds of a variety of monocotyledonous and dicotyledonous plant species were individually mixed with the soil used for growing seedlings, and planted on top to a depth of approximately one inch (25.4 mm) in a Cup with a capacity of one pint (0.568 liters). After planting, the cups are sprayed with aqueous acetone solution containing test compound. The above-mentioned test solution consisted of a 50/50 mixture of acetone/water and the test compound in sufficient quantity to ensure approximately equivalent to 0.016 kg/ha to 4.0 kg/ha of active compound when applied to the soil through the spray tip, operating at a pressure of 40 psig (2.8 kg/cm2) within a predetermined time. The treated cups were then placed on shelves in the greenhouse and cared for in accordance with known procedures.

below. The results of herbicide evaluations are expressed on a scale of 0-9. This scale is based on the visual observation of the plants, defects, size, chlorosis and General appearance of the plants compared to control.

The data obtained are collected in table. 3. When carried out more than one experiment for this connection, this is an average value.

Example 60. Herbicide evaluation test compounds after germination.

Used plant species are presented in table. 4.

Herbicide activity after germination imidazolines benzoheterocycles compounds that are the subject of the present invention was confirmed by the following tests, in which a variety of monocotyledonous and dicotyledonous plants were treated with solutions of the test compounds in aqueous acetone. The above test solutions consisted of a 50/50 mixture of acetone/water containing 0,50% NDBYF 20, monolaurate polyoxyethylene sorbitan, surface-active agent manufactured by Atlas Chemical industries, and test compounds in sufficient quantity, to ensure approximately equivalent to 0.016 kg/ha-1.00 kg/ha active with im /2.8 kg/cm AC/ within a predetermined time. In these tests the shoots of plants grown at temporary sites within approximately two weeks. Plants were sprayed test solution was placed in a greenhouse and cared for in accordance with known procedures for greenhouses.

After 4-5 weeks after treatment the plants were analyzed and evaluated in accordance with the rating system, which was described above. Herbicide activity of the compounds that are the subject of the present invention, are evident from the data listed in the table. 5, below.

If this connection is carried out by more than one test, the data are averaged.

1. Derivatives of imidazoline of the General formula

< / BR>
where A denotes a group of the formula

< / BR>
where R1hydrogen, alkyl (C1C4,

X, Y and Z are each independently CR or N, provided that at least one of X, Y and Z must be N,

R is hydrogen or alkyl (C1C4,

R2and R3alkyl, C1C4.

2. The method of obtaining derivatives of imidazoline of the General formula

< / BR>
where R1hydrogen, alkyl (C1C4,

R2and R3alkyl, C1C4,

R4alkyl, C1C4, characterized in that the Oia, with an aqueous base followed by addition of mineral acid.

 

Same patents:

The invention relates to new substituted pyrazolylborate, and to their use as herbicide compositions

The invention relates to a helical compounds of General formula 1

< / BR>
where a denotes an integer of 0 or 1, b denotes an integer equal to 2 to 5 inclusive, c is an integer of 0 or 1, and d denotes an integer of 0 to 2, inclusive; Z meansan atom of oxygen or sulfur, where R1means a hydrogen atom, an amino group, monoalkylamines from 1 to 6 carbon atoms, dialkylamino containing 1 to 6 carbon atoms in the alkyl group, hydroxyl group, alkoxygroup from 1 to 6 carbon atoms or a hydroxyalkyl group of 1 to 6 carbon atoms; R2means a hydrogen atom, alkyl group of 1 to 6 carbon atoms, a hydroxyalkyl group of 1 to 6 carbon atoms, haloalkyl group of 1 to 6 carbon atoms, formyl group or alkylcarboxylic group of 2 to 7 carbon atoms, R3means a hydrogen atom or alkyl group of 1 to 6 carbon atoms; Q represents a structural fragment of formula II

< / BR>
where R4means an alkyl group of 1 to 6 carbon atoms, alkenylphenol group of 2 to 6 carbon atoms, Halaal substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, alkoxygroup from 1 to 6 carbon atoms or alkylamino from 1 to 6 carbon atoms; R5means a hydrogen atom, a substituted or an unsubstituted amino group, a hydroxyl group, alkoxygroup of 1 -6 carbon atoms or a halogen atom; A denotes a nitrogen atom or awhere R7means a hydrogen atom, alkyl group of 1 to 6 carbon atoms, a halogen atom, alkoxygroup of 1 -6 carbon atoms, haloalkyl group of 1 to 6 carbon atoms or cyano; R4may, taken together with R5and/or R7to form a substituted or unsubstituted ring, which may include an oxygen atom, nitrogen or sulfur, where the Deputy is an alkyl group of 1 to 6 carbon atoms or haloalkyl group of 1 to 6 carbon atoms; X represents a halogen atom, preferably a fluorine atom; Y represents a hydrogen atom, alkyl group of 1 to 6 carbon atoms, alkoxyalkyl group of 1 to 6 carbon atoms, phenylalkyl group containing 1 to 6 carbon atoms in its alkyl fragment, group dihalides boron, phenyl group, acetoxymethyl group, pivaloyloxymethyl group, ethoxycarbonylethyl, politikatol-4-ylmethylene group or 3-acetoxy-2-oxobutyl group, and the salts of these compounds

The invention relates to new derivatives of 3-aminopyrazole possessing biological activity, and to their use in farbkomposition

The invention relates to new derivatives of pyrazole and their pharmaceutically acceptable salts

The invention relates to a simple ester of (thio)-morpholinyl and piperazinil-alkyl phenols of the formula

(I) their salts accession acids and their stereochemical isomeric forms, while Het is a heterocycle of the formula

Ror< / BR>
R6is hydrogen, C1-C4-alkyl, halogen, actigraphy, trifluoromethyl, cyano, C1-4-alkyloxy-FROM1-4-alkylthiophene,1-4-alkylthio (alkylsulfonyl)1-4-alkylsulfonyl,1-4-allyloxycarbonyl,1-4-alkylcarboxylic or aryl;

R7and R8each independently is hydrogen or C1-4-alkyl;

R9is hydrogen, halogen, amino, C1-4-alkyl, trifluoromethyl or aryl;

R10is hydrogen, halogen, amino or nitro-group;

R11is hydrogen, C1-4-alkyl, C1-4-alkyloxyalkyl, WITH1-4the alkyl or aryl-C1-4-alkyl;

n is an integer from 1 to 4 inclusive;

R1and R2each independently is hydrogen, C1-4-alkyl or halogen;

R3is hydrogen, halogen, cyano-C1-4-alkyloxy, aryl or-СОOR4and R4is hydrogen, C1-4-alkyl, aryl-C1-4-alkyl, C3-6-cycloalkyl-C1-4-alkyl, C3-5-alkenyl,3-5-quinil or1-4-alkyloxy-C1-4-alkyl, or R3is a radical of the formula

or< / BR>
R12and R13each independently is hydrogen, C1-4the alkyl, aryl or aryl-C1-4-alkyl;

each aryl is phenyl, optionally substituted by one or two substituents, each independently selected from halogen, C1-4-alkyl, trifloromethyl,1-4-alkyloxy or actigraphy

The invention relates to new derivatives of 1-phenyl-3-azabicycloalkanes-2-ones, to a method for producing them, to pharmaceutical compositions containing them and to their use as therapeutic agents

The invention relates to new pyridazinyl, derivatives which have the General formula:

(1) where one or two carbon atoms of methylene groups in the residue-NX - can be substituted by alkyl WITH1-C4, alkoxygroup1-C4or two carbon atom of the methylene groups of the above-mentioned residue can be connected by bridge with alkane(C2-C4)delovym radical; X represents CH or a nitrogen atom; each of m and n, independently of one another, denotes 1, 2, 3, and the sum m+n is 3, 4 or 5; R1denotes a hydrogen atom, alkyl WITH1-C4the halogen atom; each of R2and R3independently denotes a hydrogen atom or alkyl WITH1-C4; Аlк denotes alkane(C1-C4)diyl, each of R4and R5independently denotes hydrogen atom or halogen atom, or WITH1-C4-alkyl, and Неt denotes the group of one of formulae

where R6denotes a hydrogen atom, alkyl (C1-C6), oxyalkyl(C1-C6), cycloalkyl(C3-C6), phenyl or amino; each of R7independently denotes a hydrogen atom, alkyl (C1-C6), cycloalkyl(C3-C6), phenyl or trifluoromethyl, and their salts or a stereochemical isomeric form

The invention relates to new biologically active compounds derived from 4-oxo-1,4-dihydropyrimidin having antiallergic activity, which can find application in pharmaceutical industry and medicine

The invention relates to chemical-pharmaceutical industry, namely to new biologically active substances on the basis of which can be created drugs with hypotensive and analepticheskih activity

The invention relates to new benzofuranol derivatives, process for their preparation and to contain these compounds in pharmaceutical compositions

The invention relates to new chemical compound - complex 1-ethylimidazole with ascorbate zinc (eskazole) formula

enhance the body's resistance to the action of nitrogen dioxide and has cytoprotective and antihypoxant activity (N state of registration 10191991)

FIELD: chemistry.

SUBSTANCE: invention relates to synthesis of 11-(21-alkylimidazolinyl-11)-2-[(21- alkylimidazolinyl-11)poly(ethylene-N-alkanoylamido)]ethane, capable of increasing adhesion of asphalt to mineral materials, which can be used in industrial and road construction when building roads, aerodromes, roofs, waterproof coatings etc. Said compound is used as an adhesive additive, rubber is used as a structure-forming additive and the plasticiser used is a liquid fraction of low-molecular weight polyethylene and/or a fraction of C20-C26 alpha-olefins and/or propylene pentamers. Components of the binder are used in a certain quantitative ratio.

EFFECT: compounds have high adhesion to road surface mineral materials and high temperature stability, thereby improving plasticity of the asphalt binding material.

2 cl, 3 tbl, 3 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of 2-(azol-1-yl)ethaneamines that are used as the parent compounds in preparing biologically active compounds of medicinal and agriculture designation. Method for synthesis of 2-(azol-1-yl)ethaneamines of the general formula (I): wherein R1 means hydrogen atom or alkyl group comprising from 1 to 6 carbon atoms; each Z and X means independently -CH or nitrogen atom (N); or Z and X mean in common group -C-CH=CH-CH=CH-C that forms a system anellated with azole cycle involves the alkylation reaction of azole compounds wherein R1, Z and Y have the same values as in the formula (I) with oxazolines of the formula (II): wherein R2 means alkyl group comprising from 1 to 6 carbon atoms, phenyl, halogenphenyl group in the presence of Lewis acid or protonic acid to yield N-[2-(azol-1-yl)ethyl]alkaneamides of the formula (III): wherein R1, R2, Z and X have above given values followed by their hydrolysis in the presence of acids or bases in polar solvent medium at temperature 60-120°C.

EFFECT: improved method of synthesis.

5 cl, 17 ex

FIELD: organic chemistry, medicine, veterinary science, cosmetology.

SUBSTANCE: invention relates to agents used for accelerating processes for tissues regeneration and especially in presence of inflammatory processes accompanied with infection with pathogenic microflora. Invention describes 1,3-dialkylbenzimidazolium halides of the general formula: wherein R1 and R2 mean Alk; X- means F-, Cl-, Br-, J- that possess regenerating, anti-inflammatory and antibacterial activity. Invention provides preparing group of compounds of 1,3-dialkylbenzimidazolium monohalides possessing valuable biological properties. Invention can be used in pharmaceutical industry and cosmetology.

EFFECT: valuable properties of compounds.

5 tbl, 1 dwg, 1 ex

FIELD: organic chemistry, chemical technology.

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

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

8 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of 1,2-disubstituted 2-aminobezimidazole, and more specifically to 2-(9-anthrylmethyl)amino-1-[2-(1-pyrrolidinyl)ethyl]benzimidazole of formula I: , which have properties of fluorescent chemosensor on H+ cations.

EFFECT: obtaining new fluorescent chemosensor on H+ cations.

1 dwg, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there is described a compound of formula I: or its pharmaceutically acceptable salt, where R2 represents (CR3R4)n-NR5R6 and m, p, q, Ar, R1, R3, R4, R5 and R6 are those as specified in the patent claim and defined as selective 5-NT6 and/or 5-NT2A antagonists. There is also described a pharmaceutical composition containing this compound, and application thereof in preparing drugs for treating diseased conditions of central nervous system chosen from psychoses, schizophrenia, manic depressions, neural disorders, memory impairment, attention deficient syndrome, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, malnutrition and Huntington's disease.

EFFECT: preparation of the compounds which can find application in treatment of a diseased condition of central nervous system.

27 cl, 1 tbl, 29 ex

FIELD: chemistry.

SUBSTANCE: disclosed compounds can be used as a medicinal agent having CXCR2 inhibiting properties. In formula I , X denotes -CR3=CR4-, -CR5=N-, -N=CR6-, -NR7- or -S-; R3, R4, R5 and R6 independently denote hydrogen, F, CI, Br, I; R7 denotes hydrogen; Y1, Y2, Y3 and Y4 independently denote -CR8- or nitrogen, provided that at least two of Y1, Y2, Y3 and Y4 denote -CR8-; where R8 denotes hydrogen, F, CI, Br, I; A denotes a cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms; a bicyclic partially saturated 9-member cycloalkyl; a bicyclic partially saturated 9-10-member heterocycle in which two atoms in the ring are oxygen atoms; phenyl; naphthyl; a 5-6-member heteroaryl in which 1-3 atoms in the ring are oxygen, sulphur and nitrogen atoms; a 9-10-member bicyclic heteroaryl in which 1-3 atoms in the ring are nitrogen, oxygen and sulphur atoms; a 6-member heterocycle in which one atom in the ring is a nitrogen atom and which can be unsubstituted or substituted with alkyl having 1, 2, 3 or 4 carbon atoms, -C(O)CH3, -C(O)CH2CH3, -C(O)cyclopropyl, -C(O)CF3 and -C(O)OC(CH3)3; where phenyl, heterocyclic or heteroaryl radical is substituted with 1, 2 or 3 radicals selected from a group consisting of F, O, Br, I, OH, CN, NO2, SCF3, SF3, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; cycloalkyl having 3, 4, 5 or 6 carbon atoms; alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; -S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; -NR9R10, C(O)R44, S(O)SR47, -(CH2)k-phenyl, 5-6-member heteroaryl, in which 1-3 atoms in the ring are nitrogen and sulphur atoms; where the phenyl radical may be substituted with F, CI, Br, I; R9 is an alkyl having 1, 2, 3 or 4 carbon atoms; R10 is an alkyl having 1, 2, 3 or 4 carbon atoms; R44 is an alkyl having 1, 2, 3 or 4 carbon atoms, where 1, 2, 3 hydrogen atoms may be substituted with fluorine atoms; alkoxy having 1, 2, 3 or 4 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms; R47 is an alkyl having 1, 2, 3 or 4 carbon atoms; k equals 0, 1, 2 or 3; s equals 1 or 2; B is -O-C(R11R12), -C≡C-, -CR52=CR53-, -C(R13R14)C(R15R16), -NR17-C(R18R19); R11, R12, R13, R14, R15, R16, R17, R18, R19, R52, R53 independently denote hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; D is C(O)OH, C(O)NHR21 or C(=NR58)NHR22; R21 and R22 independently denote hydrogen, -SO2-alkyl having 1, 2, 3 or 4 carbon atoms, -SO2-phenyl; R58 is OH; R1 and R2 independently denote an alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, where the alkyl radicals are unsubstituted or substituted with 1 radical selected from a group consisting of F, Cl, Br, I, phenyl substituted with OH; or R1 and R2, taken together with a carbon atom with which they are bonded form a 3-, 4-, 5- or 6-member carbocycle. The invention also relates to use of formula I compounds in preparing a medicinal agent which has CXCR2 inhibiting properties, to a medicinal agent which containing an effective amount of the disclosed compound and having CXCR2 inhibiting properties, as well as to use of formula II compounds (formula and values of radicals are given in the formula of invention) in preparing a medicinal agent having CXCR2 inhibiting properties.

EFFECT: high effectiveness of application.

10 cl, 384 ex

Up!