Improved method of producing medetomidine or non-toxic pharmaceutically acceptable salts thereof

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to a method of producing 4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole, also known as medetomidine, having structural formula I: , which involves alkylation of N-trimethylsilyl imidazole with 2,3-trimethylbenzyl chloride in the presence of titanium tetrachloride in the medium of chlorine-containing organic solvents with molar ratio with 2,3-trimethylbenzyl chloride: trimethylsilyl imidazole:TiCl4 equal to 1.0:4.0-5.0:3.6-4.5.

EFFECT: improved method of producing medetomidine, characterised by high output of the end product.

1 tbl, 1 ex

 

The invention relates to the field of pharmaceutical chemistry, specifically to an improved method of obtaining 4-[1-(2,3-dimetilfenil)ethyl]-1H-imidazole, also known as medetomidine, which corresponds to the structural formula I:

Medetomidin - selective agonist α2-adrenergic receptors and sedative, analgesic, hypnotic and anxiolytic action. Medetomidin is the current top of veterinary drug Domitor, and its D-isomer - medical drug Precedex.

There are several ways of obtaining medetomidine.

In US patent No. 4443466 (or patent SU 1241990), publ. 15.02.1983, C07D 233/54) describes a method of obtaining benzylamine of imidazoles, including medetomidine. The method consists in the fact that conduct consistently reaction of 2,3-dimethylphenylethylamine and methylacrylamide with ether 4-imidazolecarboxamide acid to obtain 4-[[α-(2,3-dimetilfenil)-α-methyl]oxymethyl]imidazole, followed by dehydration of the obtained tertiary alcohol to obtain the corresponding alkene, which hydronaut to medetomidine.

In WO 2009053709 (A1), publ. 30.04.2009, C07D 233/54, describes the interaction of N-trimethylsilylimidazole and 2,3-di-α-methylbenzylamino alcohol in the presence of a Lewis acid such as titanium tetrachloride in chlorinated rest retele, for example anhydrous methylene chloride, at a temperature of less than or about 45°C., preferably at a temperature of about 30°C. When the molar ratio of dimethyl-methylbenzylamino alcohol to N-trimethylsilylimidazole is from 1:2 to 1:8, mainly 1:4 or 1:3 (page 6 of the description), and dimethyl-methylbenzylamino alcohol to the Lewis acid of 1:2-1:8.

L.V.Kudzma, S.P.Tumbml, Synthesis 1991, p.1021-1022, describe getting medetomidine by acylation bisamidines imidazole-acid chloride 2,3-dimethylbenzoic acid; hydrolysis derived to 4-(2,3-dimethylbenzyl)imidazole, the interaction of the latter with methyllithium and restoration of the intermediate compounds to medetomidine.

The disadvantage of each of the above methods is either not a high yield of the obtained product, or a multi-stage and complexity in the implementation of methods with the use of Grignard reagents.

In EP 0072615 B1, publ. 23.02.1983, C07D 233/58 described several ways of obtaining medetomidine or its non-toxic pharmaceutically acceptable additive salts. The closest to the method proposed according to the present invention, a method of obtaining medetomidine or its pharmaceutically acceptable salts by alkylation of N-trimethylsilylimidazole 1-chloro-1-(2,6-dimetilfenil)ethane (α,2,3-trimethylbutyramide) when outstay a Lewis acid for example, titanium tetrachloride, in dry chloroform or methylene chloride with a stoichiometric ratio of N-trimethylsilylimidazole and 1-chloro-1-(2,6-dimetilfenil)ethane. The process is carried out in 6-12 hours. The yield of 2,6-dimethyl analogue of medetomidine at a molar ratio of N-trimethylsilylimidazole : titanium tetrachloride : α,2,3-trimethylbenzoic 1:1,4:1 is 33%.

The disadvantage of this method is the low yield of the target substance.

The objective of the invention is to simplify the process of obtaining and increasing the yield of medetomidine.

The problem is solved proposed according to the present invention a method of receiving medetomidine or its non-toxic pharmaceutically acceptable additive salts. The method consists in the fact that N-trimethylsilylimidazole subjected to alkylation of 2,3-trimethylbutyramide in the presence of titanium tetrachloride in the environment of chlorine-containing organic solvent.

The difference of the proposed method from the previously known is that the process is carried out at a molar ratio of 2.3-trimethylbenzoic : trimethylsilylimidazole : TiCl41,0:4,0-5,0:3,6-4,5. When the molar ratio of titanium tetrachloride to N-trimethylsilylimidazole should not exceed 1, mainly of 0.95, and the molar ratio of titanium tetrachloride to α,2,3-trimethylbenzyl the chloride must be greater than 1.

When the molar ratio of titanium tetrachloride to N-trimethylsilylimidazole equal to 1.0 and above, there is a sharp decrease in the output of medetomidine to 20% and below.

Increasing the molar ratio of N-trimethylsilylimidazole α,2,3-trimethylbutyramide from 1.2 to 5.0 increases the output of medetomidine (α,2,3-trimethylbenzoic) from 62 to 84%.

The predominant molar ratio of α,2,3-trimethylbenzoic : N-trimethylsilylimidazole : TiCl4is 1.0:5,0:4,5. In this case, the method allows to increase considerably the output of medetomidine, which reaches 84%.

As the organic solvent can be used methylene chloride, chloroform, 1,1-dichlorethylene. The ratio solvent/reagent has no significant impact on the yield of the target substance.

When processing the obtained medetomidine non-toxic pharmaceutically acceptable acid, such as hydrochloric acid, Hydrobromic acid, oxalic acid, can be obtained from the corresponding non-toxic pharmaceutically acceptable salt.

Experimental part

The described method is illustrated by the following example.

Example 1.

To a solution of 56,0 g (0.40 mol) of N-trimethylsilylimidazole in 150 ml of chloroform at room temperature under stirring for 30 minutes, add a solution to 72.2 g (0.38 mol) of titanium tetrachloride in 100 the l of chloroform. Stirred the reaction mixture for 30 minutes, then add dropwise a solution of 16,85 g (0.10 mol) of α,2,3-trimethylbutyramide in 50 ml of chloroform. The stirring is continued for 3-5 hours and poured into 300 ml of ice water.

The aqueous layer was separated, alkalinized to pH>8, is treated with ethyl ether (3×100 ml) and the ether layer separated.

From the organic layer remaining after pouring into ice-cold water, remove the solvent in vacuo, to the residue is added 200 ml of 10% solution of sodium hydroxide, the resulting mixture is treated with ethyl ether (3×100 ml), the ether layer separated.

The combined ether extract is treated with 10% solution of acetic acid (3×50 ml), the aqueous layer was separated and alkalinized to pH>8. Released medetomidin extracted with methylene chloride (3×50 ml), the organic layer dried over Na2SQ4and remove the solvent Gain of 16.4 g (82% in the calculation of α,2,3-trimethylbenzoic) 4-[1-(2,3-dimetilfenil)ethyl]-1H-imidazole (medetomidine) as a light yellow crystalline substance. NMR H1: δ 1.56 (d, 3H, J=7,3 Hz, CH-CH3), of 2.20 (s, 3H, C6H5-CH3), and 2.27 (s, 3H, C6H5-CH3), 4,36 (q, 1H, J=7,3 Hz, CH-CH3), 6,70 (s, 1H, Im, C-5), 6,94 (m, 1Harom), 7,01 (m, 2Harom), 7,37 (s, 1H, Im, C-2), a 9.60 (br s, 1H, NH). TPL171-172°C. (hydrochloride).

Precipitate received base with acid, such as hydrochloric or oxalic acid, prevadid receiving respectively hydrochloride or oxalate.

The results of the experiments with different ratios of α,2,3-trimethylbenzoic, N-trimethylsilylimidazole and titanium tetrachloride are presented in the table.

The influence of the ratio of reagents on the output of medetomidine (number α,2,3-trimethylbutyramide 0.1 mol)
№ p/pThe molar ratio of the reactantsThe solvent quantity in ml for a, b, COutput
A*B*S*
111,20,5CHCl3, 50,50,2010-15 (mix-in)
211,21,1CHCl3, 50, 50, 3062
3121,8CHCl3, 50, 75, 5075
4 4the 3.8CHCl3, 50, 150, 10082
5142CHCl3, 50, 150, 5079
6144CHCl3, 50, 150, 10020
7144,1CHCl3, 50, 150, 1008
8143,6CH2Cl2, 50, 150, 10083
9143,6CH2CCl2, 50, 150, 10080
10154,5CHCl3, 50, 150, 10084
11143,6CHCl3, 25, 75, 5081
* A - α,2,3-trimethylbenzoic. In* - N-trimethylsilylimidazole,* - TiCl4.

The claimed method of obtaining medetomidine ease and good reproducibility, the yield of the target compounds at the optimum value of α,2,3-trimethylbenzoic : N trimethylsilylimidazole : TiCl41,0:5,0:4,5 reaches 84%, much higher than previously known results. From the prior art is not obvious to implement the proposed reaction, as seen from the above data, when the change ratio cannot always be obtained a product with high output.

1. The method of receiving medetomidine formula I

or its non-toxic pharmaceutically acceptable salts by alkylation of N-trimethylsilylimidazole α,2,3-trimethylbutyramide in the presence of titanium tetrachloride in the environment chlorinated solvents, followed if necessary, by converting the compounds obtained in the non-toxic pharmaceutically acceptable salt, wherein the process is conducted at a molar ratio of N-trimethylsilylimidazole α,2,3-tributive is singleride in the interval 1,0:4,0-5,0:3,6-4,5; when this molar ratio of N-trimethylsilylimidazole to titanium tetrachloride should be the maximum, but less than 1, and the molar ratio of titanium tetrachloride to α,2,3-trimethylbutyramide must be greater than 1.

2. The method according to claim 1, characterized in that the molar ratio of α,2,3-trimethylbutyramide:N-trimethylsilylimidazole:titanium tetrachloride is 1.0:5,0:4,5.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel cyclic N,N'-diarylthioureas or N,N'-diarylureas of general formula (1), their optic (R)- and (S)-isomers and their pharmaceutically acceptable salts - antagonists of androgenic receptors. In formula (1), where: X represents oxygen or sulfur atom; m=0 or 1, mR1 represents C1-C3alkyl; R2 and R3 represent hydrogen atom; or R2 and R3 together with carbon atom, to which they are bound, form group C=O; or represents group NH; R4 and R5 represent hydrogen atom; or R4 represents hydrogen atom, and R5 represents methyl; or R4 represents hydrogen atom, methyl, and R5 represents group Zn-Y-R6, in which n=1 or 2, Z represents CH2 or C=0 and Y- oxygen atom or N-CH3, or Y represents C=O, and Z represents CH2; R6 represents hydrogen atom, methyl, benzyl, hydroxygroup or R5 and R4 together with atoms, to which they are bound, form five or sic-member heterocycle, including, at least, oxygen or nitrogen atom, which can be substituted by methyl. Invention also relates to method of obtaining compounds.

EFFECT: invention relates to anti-cancer substance, pharmaceutical composition, medication and method of treating prostate cancer with application of invention compounds.

12 cl, 6 dwg, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) in form of a separate stereoisomer, a mixture of stereoisomers or a racemic mixture of stereoisomers and their pharmaceutically acceptable salts. In formula (I) ring A, C or D is independently completely or partially saturated; each of C1, C4, C11, C12, C15 and C16 is independently substituted with two hydrogen atoms; each of C9 and C14 is independently substituted with a hydrogen atom; R1 represents -OR7 or -N(R7)2. Values of the rest of the radicals are given in the formula of invention. The invention also relates to a pharmaceutical composition with anti-inflammatory activity and contains an effective amount of the disclosed compound and to use of the said compounds to make a medicinal agent with anti-inflammatory activity.

EFFECT: disclosed compounds have anti-inflammatory activity.

23 cl, 47 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel imidazole derivatives of formula (I): and to its salts with acid, where: R1 and R2 represent hydrogen; Q represents (CH2)m-X-(CH2)n-A; A represents direct bond, O, SO2, NR5; X represents direct bond, O, SO2, C(O) or NR5; Z represents group selected from : m and n represent, each independently, 0, 1, 2, 3 or 4; p represents 1, 2, 3 or 4; q represents 0, 1 or 2; dotted line means that R8 and/or R9 can be situated in any position of benzothiophene ring; R3 and R8 represent, each independently, hydrogen or hydroxy, cyano, halogen, nitro, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl, (C1-C6)alkylthio, (C1-C6)alkylsulfonyl, acyl, (C1-C6)alcoxycarbonyl, carboxamido, NR10R11, SO2NR10R11, OSO2NR10R11 or NR12SO2NR10R11, OSO2NR12SO2NR10R11, CO2R10; when Q-Z represents n 0, 1 or 2 and p represents 1, one of R3 and R8 represents hydroxy, nitro, NR10R11, OSO2NR10R11, NR12SO2NR10R11, OSO2NR12SO2NR10R11, CO2R10, CONR10R11, and the other represents hydrogen or hydroxy, cyano, halogen, nitro, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl, (C1-C6)alkylsulfonyl, acyl, (C1-C6)alcoxycarbonyl, carboxamido, NR10R11, SO2NR10R11 OSO2NR10R11, NR12SO2NR10R11, CO2R10; R4 and R9 represent, each independently, hydrogen or hydroxy, cyano, halogen, nitro, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl, (C1-C6)alkylthio, (C1-C6)alkylsulfonyl, acyl, (C1-C6)alcoxycarbonyl, carboxamido, NR10R11, SO2NR10R11, OSO2NR10R11, NR12SO2NR10R11, OSO2NR12SO2NR10R11, CO2R10, CHO; when p represents 2, 3 or 4, R9 can be similar or different; R6 and R7 represent hydrogen; each R5, R10, R11 and R12 represents hydrogen; when Z represents and p represents 1, then R8 and R9 can also together with phenyl ring form benzoxathiazine dioxide. Invention also relates to pharmaceutical composition and to application of derivatives by any of ii.1-25.

EFFECT: obtaining novel biologically active compounds which possess inhibiting activity with respect to aromatase and/or steroid-sulfatase and/or carboanhydrase.

36 cl, 67 ex, 5 tbl

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

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 new amino acid derivatives and their pharmaceutically acceptable salts, specifically to new amino acid derivatives and their pharmaceutically acceptable salts, which have an inhibiting activity against renin, to methods for their preparation, to pharmaceutical compositions containing them and to a method for the treatment of hypertension and heart failure in humans or animals

The invention relates to the separation and purification of 2-methylimidazole, which is an intermediate for the synthesis of antitrichomonas, protivoallergennogo drug metronidazole and accelerator curing epoxy resins

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: chemistry.

SUBSTANCE: invention relates to novel imidazole derivatives of formula (I): and to its salts with acid, where: R1 and R2 represent hydrogen; Q represents (CH2)m-X-(CH2)n-A; A represents direct bond, O, SO2, NR5; X represents direct bond, O, SO2, C(O) or NR5; Z represents group selected from : m and n represent, each independently, 0, 1, 2, 3 or 4; p represents 1, 2, 3 or 4; q represents 0, 1 or 2; dotted line means that R8 and/or R9 can be situated in any position of benzothiophene ring; R3 and R8 represent, each independently, hydrogen or hydroxy, cyano, halogen, nitro, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl, (C1-C6)alkylthio, (C1-C6)alkylsulfonyl, acyl, (C1-C6)alcoxycarbonyl, carboxamido, NR10R11, SO2NR10R11, OSO2NR10R11 or NR12SO2NR10R11, OSO2NR12SO2NR10R11, CO2R10; when Q-Z represents n 0, 1 or 2 and p represents 1, one of R3 and R8 represents hydroxy, nitro, NR10R11, OSO2NR10R11, NR12SO2NR10R11, OSO2NR12SO2NR10R11, CO2R10, CONR10R11, and the other represents hydrogen or hydroxy, cyano, halogen, nitro, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl, (C1-C6)alkylsulfonyl, acyl, (C1-C6)alcoxycarbonyl, carboxamido, NR10R11, SO2NR10R11 OSO2NR10R11, NR12SO2NR10R11, CO2R10; R4 and R9 represent, each independently, hydrogen or hydroxy, cyano, halogen, nitro, (C1-C6)alkyl, (C1-C6)alkoxy, trifluoromethyl, (C1-C6)alkylthio, (C1-C6)alkylsulfonyl, acyl, (C1-C6)alcoxycarbonyl, carboxamido, NR10R11, SO2NR10R11, OSO2NR10R11, NR12SO2NR10R11, OSO2NR12SO2NR10R11, CO2R10, CHO; when p represents 2, 3 or 4, R9 can be similar or different; R6 and R7 represent hydrogen; each R5, R10, R11 and R12 represents hydrogen; when Z represents and p represents 1, then R8 and R9 can also together with phenyl ring form benzoxathiazine dioxide. Invention also relates to pharmaceutical composition and to application of derivatives by any of ii.1-25.

EFFECT: obtaining novel biologically active compounds which possess inhibiting activity with respect to aromatase and/or steroid-sulfatase and/or carboanhydrase.

36 cl, 67 ex, 5 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) in form of a separate stereoisomer, a mixture of stereoisomers or a racemic mixture of stereoisomers and their pharmaceutically acceptable salts. In formula (I) ring A, C or D is independently completely or partially saturated; each of C1, C4, C11, C12, C15 and C16 is independently substituted with two hydrogen atoms; each of C9 and C14 is independently substituted with a hydrogen atom; R1 represents -OR7 or -N(R7)2. Values of the rest of the radicals are given in the formula of invention. The invention also relates to a pharmaceutical composition with anti-inflammatory activity and contains an effective amount of the disclosed compound and to use of the said compounds to make a medicinal agent with anti-inflammatory activity.

EFFECT: disclosed compounds have anti-inflammatory activity.

23 cl, 47 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel cyclic N,N'-diarylthioureas or N,N'-diarylureas of general formula (1), their optic (R)- and (S)-isomers and their pharmaceutically acceptable salts - antagonists of androgenic receptors. In formula (1), where: X represents oxygen or sulfur atom; m=0 or 1, mR1 represents C1-C3alkyl; R2 and R3 represent hydrogen atom; or R2 and R3 together with carbon atom, to which they are bound, form group C=O; or represents group NH; R4 and R5 represent hydrogen atom; or R4 represents hydrogen atom, and R5 represents methyl; or R4 represents hydrogen atom, methyl, and R5 represents group Zn-Y-R6, in which n=1 or 2, Z represents CH2 or C=0 and Y- oxygen atom or N-CH3, or Y represents C=O, and Z represents CH2; R6 represents hydrogen atom, methyl, benzyl, hydroxygroup or R5 and R4 together with atoms, to which they are bound, form five or sic-member heterocycle, including, at least, oxygen or nitrogen atom, which can be substituted by methyl. Invention also relates to method of obtaining compounds.

EFFECT: invention relates to anti-cancer substance, pharmaceutical composition, medication and method of treating prostate cancer with application of invention compounds.

12 cl, 6 dwg, 16 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to a method of producing 4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole, also known as medetomidine, having structural formula I: , which involves alkylation of N-trimethylsilyl imidazole with 2,3-trimethylbenzyl chloride in the presence of titanium tetrachloride in the medium of chlorine-containing organic solvents with molar ratio with 2,3-trimethylbenzyl chloride: trimethylsilyl imidazole:TiCl4 equal to 1.0:4.0-5.0:3.6-4.5.

EFFECT: improved method of producing medetomidine, characterised by high output of the end product.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 4-(2,3-dimethylbenzyl)-1H-imidazole, also known as detomidine, having formula I: , which involves alkylation of trimethylsilyl imidazole with a compound of formula II: , where X: CI, Br, OH, in the presence of titanium tetrachloride in the medium of a chlorine-containing organic solvent, where molar ratio of titanium tetrachloride to N-trimethylsilyl imidazole must be maximum but must not be more than 0.95.

EFFECT: novel method of producing detomidine, characterised by high output of the end product.

1 cl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a method for preparing 2-methylimidazole involving mixing 40% aqueous glyoxal, acetaldehyde and aqueous ammonia, further recovering an end product by distillation, differing by the fact using 25% ammonia, mixing acetaldehyde and ammonia at temperature 0÷5°C; adding glyoxal preliminary purified from impurities by electrodialysis at temperature no more than 60°C; the agents taken in a ratio of ammonia : acetaldehyde : glyoxal = 2:1:1; the reaction conducted at temperature 90-95°C for 3 hours; besides, the end product recovered by vacuum distillation at residual pressure 0.5-1.5 kPa and vapour temperature 120-140°C preceded by water distillation.

EFFECT: what is developed is the new method for preparing 2-methylimidazole differing by high yield and end product quality, as well as simplified process of recovering and purifying.

2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to benzimidazole derivatives of general formula (I) and to their pharmaceutically acceptable salts, mixed stereoisomers and enantiomers, wherein R1 is L1C(O)OL2C(O)OT; R2 is unsubstituted C1-C10alkyl; L1 is a bond; L2 is unsubstituted C2-C10alkylene; T is C1-C10alkyl. Also, the invention refers to a pharmaceutical composition of the compound of formula (I) and a method of anaesthetising on the basis of using the compound of formula (I).

EFFECT: there are prepared new imidazole derivatives effective as an anaesthetising agent.

15 cl, 9 dwg, 15 ex

FIELD: pharmacology.

SUBSTANCE: compounds of the invention are intended for manufacture of a pharmaceutical composition, kit or drug. The invention also relates to a process for preparation of compounds of the invention (versions). Compounds of the invention are intended for use in the prevention or treatment of diseases caused by RNA-containing viruses belonging to enteroviruses, metapneumoviruses or pneumoviruses.

EFFECT: amide compounds for treatment or prevention of diseases caused by RNA-containing viruses.

26 cl, 8 tbl, 5 ex

Up!