替米沙坦的合成工艺优化

Optimization for the synthesis process of telmisartan

通过实验对替米沙坦(TMST)原料药的合成工艺路线进行优化,确定以3-甲基-4-氨基苯甲酸为起始原料,经酯化、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;在多聚磷酸的作用下,与N-甲基邻苯二胺缩合,产物再与4’-溴甲基联苯-2-羧酸甲酯缩合,水解得到替米沙坦,总收率约为36%。

The synthesis process of telmisartan was optimized by experiments,and 3-methyl-4-aminobenzoic acid was used as the starting material,and 2-n-propyl-4-methyl-6-carboxybenzimidazole was obtained by esterification,acylation,nitration,reduction and cyclization.The product was condensed with N-methyl-o-phenylenediamine under the action of polyphosphate,and then condensed with 4’-bromomethyl-biphenyl-2-carboxylate and hydrolyzed to telmisartan.The total yield of telmisartan was about 36%.