• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
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    • 专利摘要:
    New heterocyclylcarboxylic acid derivatives which are acylated in the nucleus, especially benz-acyl-benzimidazole-2-carboxylic acid derivatives of the formula <IMAGE> (I) in which R is a free, esterified or amidated carboxyl group or a free, etherified or esterified hydroxymethyl group, R1 is an aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic or heterocyclic-aliphatic radical, R2 is hydrogen or an aliphatic radical and Ph is a 1,2-phenylene group containing the radical R1-C(=O)-, with the proviso that R1 contains at least 2 carbon atoms if Ph is otherwise unsubstituted, R2 is ethyl and R is acetoxymethyl, and salts of such compounds having salt-forming properties, are useful as anti-allergic agents.
    公开号:SU784766A3
    申请号:SU792707652
    申请日:1979-01-15
    公开日:1980-11-30
    发明作者:Габихт Эрнст；Джорджо Феррины Пиэр；Саллманн Альфред
    申请人:Циба-Гейги Аг (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to a process for the generation of new (2) -aqueous
    O R I, —C — Ph. Where R is an esterified carboxyl group
    R ^ is an aliphatic, cycloaliphatic or aromatic residue; fifteen
    Rj is hydrogen or an aliphatic residue;
    A Ph- 1,2-phenylene group containing the remainder R 4 -C (= 0), unsubstituted or substituted with lower alkyl, lower alkoxy, hydroxy and / or halogen, having biological activity.
    The esterification reaction is well known, for example, by the reaction of carboxylic acids with fl J.
    The purpose of the invention is the synthesis of new derivatives of imidazole.
    The goal is achieved by the proposed method for obtaining compounds of 30 formulas I, which consists in the fact that the compound of the formula
    n B1 -C-RN ^ I > -X, (I]
    I x g where X is a carboxyl group or anhydride, 'is reacted with an alcohol, an oxonium salt, an N, N-lowering alkylformamide acetal or with an organic carbonate, pyrocarbonate, sulfite or phosphite.
    According to the proposed method, when X represents a carboxyl group in the compound of formula 11, the process is carried out using an organic pyrocarbonate in the presence of trinized alkylamine or using an oxonium salt in the presence of alkali metal hydroxide, or using Ν, ди-lowering alkylformamide acetal in a neutral medium.
    Example!. 2.5 g of 5-butyryl-6-methyl-benzimidazole-2-carboxylic acid are dissolved in 100 ml of 0.1 N sodium hydroxide solution and 14.5 g of sodium carbonate are added. To the resulting suspension, 38 g of triethyloxonium tetrafluoroborate are added portionwise over 10 minutes. Then stirred for another 30 minutes, extracted with ethyl acetate, washed twice with water, dried with sodium sulfate and evaporated to dryness. The evaporation residue 3 is chromatographed over 100 g of silica gel with chloroform as solvent. Get 5-butyryl-6-methylbenzimidazole-2-carboxylic acid ethyl ester with so pl. 142-144 ° C. · * Example 2. A mixture of 2.5 g of 5-butyryl-6-methylbenzimidazole ~ 2-carboxylic acid, 1.91 g of dimethylform ^ middiethylacetal and 25 ml of acetonitrile is kept for 2 days at room temperature 15 with the exception humidity and shaking occasionally. ' Then acetonitrile is distilled under reduced. by pressure, the residue was partitioned between ethyl acetate and sodium bicarbonate, the neutral phase was washed with water, evaporated and chromatographed on alumina with a mixture of chloroform-ethanol (9: 1) to give 5-butyryl-6-methylbenzimidazole-2- ethyl ether carboxylic acid with so pl. 142-144 ° C.
    Example 3. To a mixture of 62.9 g of diethyl pyrocarbonate, 100 ml of triethylamine and 500 ml of acetonitrile, 19.1 g of 5-butyryl-6-methylbenzimidazole-2-carboxylic acid are added over 5 minutes with stirring. It is additionally stirred at room temperature for 1 hour and then for 6 hours under heating to a boil, evaporated under reduced pressure to dryness, dissolved in ethyl acetate, washed with sodium bicarbonate solution and twice with water, dried with sodium sulfate, evaporated and ethyl acetate is recrystallized from the mixture. acids - methylene chloride.
    5-Butyryl-6-methyl-benzimidazole-2-carboxylic acid ethyl ester is obtained with a melting point of 146-147 S.
    Example 4. To a solution of 18.9 g of 2-ethoxymethyl-5-butyryl-6-methylbenzimidazole in 380 ml of acetone, 9.5 ml of pyridine and 5.7 ml of water, cooled to 45 10 ° C, 15 g of potassium permanganate are added. The mixture is stirred for another 1 h under ice-cooling and 40 h at room temperature, filtered, evaporated under reduced pressure, dissolved in ethyl acetate, washed with gg sequentially with sodium bicarbonate pH 6 and twice with water, dried with sodium sulfate and evaporated under reduced pressure, Then dissolved in 30 ml of heated acetic ether, maintained overnight 40 and crystalline ethyl ether 5-butyryl-6-methylbeneimidazole-2-carboxylic acid with so pl. 137139 ° C. Another product can be obtained from the mother liquor with mp 129-65
    132 with C. Recrystallization from a mixture of ethyl acetate, methylene chloride, up to 146147 ° C.
    Example 5. To a mixture of 150 ml of acetonitrile, 15 ml of triethylamine and 18.5 diethyl pyrocarbonate, 6.0 g of 5-butyryl-1,6-dimethylbenzimidazole-2-carboxylic acid was added over 15 minutes with stirring and at room temperature. It is maintained overnight, acetonitrile is distilled off under reduced pressure, dissolved in ethyl acetate, washed with water, dried with sodium sulfate and evaporated to dryness. Received sleep. The oily and then crystallizing ethyl ester of 5-butyryl-1, b-dimethylbenzimidazole-2-carboxylic acid is filtered off with suction. Recrystallized from a mixture of ethyl acetate, cyclohexane, it melts at 106-108 o C.
    "Example 6. Analogously to example 3, starting from 10.1 g of 5-butyryl-1-methylbenzimidazole-2-carboxylic acid and 20 g of diethylpyrocarbonate, 5-butyryl-1.-methylbenzimidazole ethyl ester is obtained -2-carboxylic acid with so pl. 115-117 ° C,
    PRI me R 7. Similar to the examples.
    1-6, the following compounds can be prepared:
    2- ethoxymethyl-5-butyryl-6-methylbenzimidazole-2-methanol with a melting point of 46-47 ° C, 5-butyryl-1,6-dimethylbenzimidazole-2-carboxylic acid isopropyl ester with mp. 90-91 ° C.
    权利要求:
    Claims (2)
    [1]
    This invention relates to the way in which new benzacylbeneimidaeol (2) is produced by the aqueous formulas J.-d. -Pk, where R is an esterified carboxyl ester R - an aliphatic, cycloaliphatic OR aromatic residue; Rj is hydrogen OR aliphatic residue; Ph-1,2-phenylene group containing a residue (0). Unsubstituted OR substituted by lower alkyl group by a lower alkoxy-group AND / OR halogen with biological activity. A widely known esterification reaction, for example, the interaction of carboxylic ACIDS with alcohols p. . The purpose of the invention is the synthesis of new imidazole derivatives. This goal is achieved by the proposed method of obtaining a compound of the Scientific Research Institute of Formula 1, which consists in the fact that the compound of the formula. R, -C-Ph where X is a carboxyl group or an anhydride, is reacted with an alcohol, oxonium salt, N, N-DIESEL alkyl formamide acetal or organic carloate, pyrocarbonate, sulfite, OR phosphite. According to the proposed method, when in the compound of the formula I, X represents a carboxyl group, the process is carried out with an organic pyrocarbonate in the presence of trinisome alkylamine or with oxonium SALT in the presence of an alkali metal hydroxide, or with N, N-lower alkyl alkylformamide in neutral medium. Example. 2.5 g of 5-butyryl-6-methyl-benzimidazole-2-carboxylic acid is dissolved in 100 ml of 0.1N sodium hydroxide solution and 14.5 g of sodium carbonate is added, to the resulting suspension is added in portions for 10 min 38 g of triethyloxonium tetrafluoroborate. Then it is stirred for another 30 minutes, extracted with ethyl acetate, washed twice with water, dried with sodium sulfate and evaporated to dryness. The residue after evaporation is chromatographed on 100 g of silica gel with chloroform as solvent. 5-Butyryl-6-methylbenzimidazole 2-carboxylic acid ethyl ester is obtained with m.p. 142-144 0. Example 2. A mixture of 2.5 g of 5-6-uryl-6-methylbnzimidazole-2-carboxylic acid, 1.91 g of dimethylformamide diethyl II; etal and 25 ml of acetonitrile are kept for 2 days at room temperature with the exclusion of humidity and with shaking from time to time. The acetonitrile is then distilled under reduced pressure. the residue is distributed between ethyl acetate and sodium bicarbonate solution, the neutral phase is washed with water, evaporated and chromatographed on alumina with a mixture of chloroform-ethanol (9: 1) and 5-butyryl-6-methylbenzimidazole ethyl ester is obtained -2-carboxylic acid with so pl. 142-144 ° C. Example To a mixture of 62.9 g of diethylpyrocarbonate, 100 ml of triethylamine and 500 ml of acetonitrile, 19.1 g of 5-butyryl-6-methylbenzimidol-2-carboxylic acid are added with stirring over 5 minutes. Stir additionally at room temperature for 1 hour and then b at heating to boiling, evaporate under reduced pressure until dry, dissolve in ethyl acetate, wash with sodium bicarbonate solution and twice with water, dry the sodium sulfate, evaporate and recrystallize from mixtures of ethyl acetate - methylene chloride. Get ethyl efcr 5-butyryl-6-methyl-benzimidazole-2-carboxylic acid with so pl. 146-147 C. Example4. To a solution of 18.9 g of 2-ethoxymethyl-5-butyryl-b-methylbenzimidazole in 380 ml of acetone, 9.5 ml of pyridine and 5.7 ml of water cooled to 10 ° C and cooled to 10 ° C, 15 g of potassium permanganate are added with stirring. Pere. stir for another 1 hour while cooling with ice and 40 hours at room temperature, filter, evaporate under reduced pressure, dissolve in acetic acid ethyl ester, wash successively with sodium bicarbonate buffer solution with pH 6 and two drops with water, dry with sodium sulfate and pack under reduced pressure. The solution is dissolved in 30 ml of heated acetic ether, incubated overnight, and the crystalline ethyl 5-butyryl-6-methylbenzimidazul-2-carboxylic acid ester is sucked off with a mp. 137HZE S. From the mother liquor, you can get another product with so pl, 129132 0. By recrystallization from a mixture of ethyl ester of acetic acid - methylene chloride increase so pl. to 146147s. Example5. To a mixture of 150 ml of acetonitrile, 15 ml of triethylamine and 18.5 diethylpyrocarbonate, with stirring and at room temperature, 15.0 g of 5-butyryl-1, 6-dimethylbe, nzimidazole-2-carboxylic acid are added over 15 minutes . Stand overnight, distill off acetonitrile under reduced pressure, dissolve in ethyl acetate, wash with water, dry with sodium sulfate, and evaporate to dryness. Received sleep-. The oily and then crystallized ether ethyl ester of 5-butyryl-1, 6-dimethylbenzimidazole-2-carboxyethyl acid is sucked off. The acetic acid ethyl ester-cyclohexane, recrystallized from a mixture, melts at 106-108 C. Example 6, analogously to Example 3, starting from 10.1 g of 5-butyryl-1-methylbenzimidazole-2-carboxylic acid and 20 g of diethylpyrocarbonate, 5-butyryl-1.-methylbenzimidazole-2-carboxylic acid ethyl ester is obtained, m.p. 115-117 C, PRI me R 7. Similar to the examples. 1-6, the following compounds can be prepared: 2-ethoxymethyl-5-butyryl-6-methylbenzimidazole-2-methanol with mp. 46-47 ° C, isopropyl ester of 5-butyryl-1,6-dimethylbenzimidazole-2-carboxylic acid with so pl. 90-91 ° C. Claim 1, Method for preparing benacylbenzi. Imidazole (2)-derivatives of the formula Phr tc-H. 1- ° --XK g where R is an esterified carboxyl group into an ester; RJ is an aliphatic, cycloaliphatic or aromatic residue; yl-hydrogen or aliphatic residue; a ph-1,2-phenylene group containing a residue (0), lower alkyl, lower alkoxy, hydroxy and / or halogen, O. distinguished by the fact that the compound of the formula k, -C-Ph 578 where X is a carboxyl group or an anhydride , is reacted with an alcohol, oxonium salt, NN-di-lower alkyl formamide acetal or with organic carbonate pyrocarbonate, sulfite or phosphite, with the release of the desired product. 2. The method according to claim 1, of which it is in the case when, in the compound of the formula P, X is a carboxyl group, the process is carried out with the help of organic pyrocarbonate in the presence of trinisome alkylamine. 3. The method according to claim 1, distinguished by the fact that in the case when in 7666 the compound of formula Ii X represents a carboxyl group, the process is carried out using oxonium salt in the presence of an alkali metal hydroxide, 4. Method pop.1 , and with the fact that in the case when in the compound of the formula P, X is a carboxyl group, the process is. carried out with the help of N, N-di-lower alkyl formamide acetal in a neutral medium. Sources of information taken into account in the examination 1. Bksher K., Pearson D. Organic 15 syntheses, h.
    [2]
    2. M., Mir, 1973, p.
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    引用文献:
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    法律状态:
    优先权:
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    LU75684A|LU75684A1|1976-08-27|1976-08-27|
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