Method for preparing telmisartan

A technology for telmisartan and a compound, which is applied in the field of preparation of antihypertensive drugs, can solve the problems of being unfavorable to industrialized production, cumbersome operation, low overall yield and the like, and achieves remarkable economic benefits, reasonable route and improved yield. Effect

Inactive Publication Date: 2012-10-17
HAIMEN CITY CHEMGOO PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The overall yield is not high, and the operation is cumbersome, which is not conducive to industrial production

Method used

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  • Method for preparing telmisartan
  • Method for preparing telmisartan
  • Method for preparing telmisartan

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Embodiment 1 prepares telmisartan

[0022] 2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2-yl)benzimidazole (30.4g, 0.10mol) shown in formula I, 4-bromomethylbi Benzene-2-carboxylic acid (43.6g, 0.15mol), potassium carbonate fine powder (30g, 0.2mol) mixed with DMSO 500ml, reacted at 100°C for 10 hours, poured the reaction solution into ice water, and slowly adjusted to pH2-3, solid precipitated. Filter and dry at 70°C to obtain a crude product, which is heated and beaten once with 300 ml of ethyl acetate. Filter and dry at 70°C. Recrystallized from DMF to obtain 44.2 g of telmisartan represented by formula III, yield: 86.5%.

[0023] Wherein, the DMSO can be replaced by any one of DMF, dioxane, pyrrolidones, butanone, 2-methylisobutyl ketone and ethylene glycol dimethyl ether.

Embodiment 2

[0024] Embodiment 2 prepares telmisartan

[0025] 2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2-yl)benzimidazole (30.4g, 0.10mol) shown in formula I, 4-bromomethylbi Benzene-2-carboxylic acid (37.83g, 0.13mol), potassium hydroxide (5.6g, 0.10mol) and 500ml of 2-methylisobutyl ketone were mixed, reacted at 80°C for 16 hours, and poured the reaction solution into ice water , Slowly adjust the pH to 2-3 with dilute hydrochloric acid, and precipitate a solid. Filter and dry at 70°C to obtain a crude product, which is heated and beaten once with 300 ml of ethyl acetate. Filter and dry at 70°C. Recrystallized from DMF to obtain 38.8 g of telmisartan represented by formula III, yield: 76%.

[0026] Wherein, the 2-methylisobutyl ketone can be replaced by any one of DMF, DMSO, dioxane, pyrrolidones, butanone and ethylene glycol dimethyl ether.

Embodiment 3

[0027] Embodiment 3 prepares telmisartan

[0028] 2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2-yl)benzimidazole (30.4g 0.10mol) shown in formula I, 4-bromomethylbiphenyl -2-Carboxylic acid (43.6g, 0.15mol), sodium ethoxide (13.6g, 0.2mol) mixed with 500ml of N-methylpyrrolidone, reacted at 50 degrees Celsius for 10 hours, poured the reaction solution into ice water, and slowly Adjust the pH to 2-3 and precipitate a solid. Filter and dry at 70°C to obtain a crude product, which is heated and beaten once with 300 ml of ethyl acetate. Filter and dry at 70°C. Recrystallized from DMF to obtain 27.7 g of telmisartan represented by formula III, yield: 54%.

[0029] Wherein, the N-methylpyrrolidone can be replaced by any one of DMF, DMSO, dioxane, other pyrrolidones, 2-methylisobutyl ketone, butanone and ethylene glycol dimethyl ether.

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Abstract

The invention discloses a method for preparing telmisartan, which can be used for directly producing telmisartan by carrying out nucleophilic substitution reaction on 2-n-propyl-4-methyl-6-(1'-methyl benzimidazole-2-yl) benzimidazole and 4-brooethyl diphenyl-2-carboxylic acid under the action of acid-binding agent. The method is simple in operation, thus improving the yield of the final product and being suitable for the synthetic route of telmisartan in industrial production.

Description

technical field [0001] The present invention relates to a preparation method of antihypertensive drugs, in particular, the present invention relates to a preparation method of Telmisartan (Telmisartan). Background technique [0002] Telmisartan is a novel non-peptide angiotensin (AT) with the following structure: [0003] [0004] The existing synthetic route of telmisartan mainly takes 3-methyl-4-aminobenzoic acid methyl ester as the starting material to obtain the intermediate through N-acylation, nitration, reduction, cyclization, ester hydrolysis and condensation reaction. 2-n-propyl-4-methyl-6-(1'-methylbenzimidazol-2-yl)benzimidazole, and 4-bromomethylbiphenylcarboxylate (R=CH 3 ,C 2 h 5 , t-Bu) nucleophilic substitution to obtain compound IV, and then hydrolyzed to the final telmisartan (Chinese patent CN 1344712A). In the preparation method, the carboxyl group of 4-bromomethylbiphenylcarboxylic acid is protected with methyl group, ethyl group or tert-butyl gro...

Claims

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Application Information

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IPC IPC(8): C07D235/18
Inventor 吴绍伟陶伟坚沈磊张达
Owner HAIMEN CITY CHEMGOO PHARMA
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