盐酸阿考替胺的合成工艺改进

Improved Synthetic Method of Acotiamide Hydrochloride

以2-羟基-4,5-二甲氧基苯甲酸为原料,在N,N′-羰基二咪唑(CDI)作用下与2-氨基噻唑-4-甲酸甲酯缩合得到2-[(2-羟基-4,5-二甲氧基苯甲酰基)氨基]-4-噻唑羧酸甲酯,与N,N-二异丙基乙二胺在甲醇钠饱和溶液∶二噁烷(1∶8)体系中回流反应2.5 h,最后与盐酸成盐得到盐酸阿考替胺,总收率约85%。

Acotiamide hydrochloride was synthesized from 2-hydroxy-4,5-dimethoxybenzoic acid by condensation with methyl 2-aminothiazole-4-carboxylate in the presence of N,N＇-carbonyldiimidazole to give methyl 2-[ （2-hydroxy-4,5-dimethoxybenzoyl）amino]-4-thiazolecarboxylate, which was subjected to acylation with N,N- diisopropylethane-1,2-diamine in saturated solution of sodium methoxide/dioxane, followed by salificatoin with an overall yield of about 85 %.