替米沙坦的合成工艺改进

An Improved Synthetic Method of Telmisartan

以3-甲基-4-硝基苯甲酸(Ⅰ)为起始原料,经多步反应合成了替米沙坦(Ⅸ)。3-甲基-4-硝基苯甲酸经酯化、还原、酰化、硝化、还原、环合反应得到2-正丙基-4-甲基-6-羧基苯并咪唑(Ⅶ),在多聚磷酸的作用下Ⅶ与N-甲基邻苯二胺缩合,生成的产物(Ⅷ)再与4′-溴甲基联苯-2-羧酸甲酯缩合、水解得替米沙坦Ⅸ。其总收率从1993年文献[3]的20.9%提高到30%。该产品已在河南天方药业股份有限公司中试。

Telmisartan was synthesized through muhistep reactions with 3-methyl-4-nitrobenzoic acid as starting material. 3-Methyl-4-nitrobenzoic acid via esterification, reduction, butyrylation, nitration, reduction and cyclization gave 2-n-propyl-4-methyl-6-carboxybenzimidazole, which condensed with Nmethyl-o-phenylenediamine in the presence of polyphosphoric acid and followed by condensation with 4＇-bromomethyl-biphenyl-2-carboxylic acid methyl ester and hydrolysis to give Telmisartan. The overall yield was improved from 20. 9% to 30%. It has been produced in Henan Tianfang Phamaceutical Co. Ltd.