一种改进的依替唑仑合成方法

An Improved Synthesis of Etizolam

依替唑仑是一种在临床上应用较为广泛的镇静、催眠、抗抑郁药。以2-氨基-3-(2-氯苯甲酰)-5-乙基噻吩(Ⅰ)为原料,经氯乙酰化,再在乙醇中与乌洛托品环合,制得关键中间体(Ⅲ)。中间体(Ⅲ)经硫化、环合反应制得依替唑仑(Ⅴ),4步反应总收率为56.4%。改进后的反应具有合成路线短、条件温和、操作简便、收率高等优点。

Etizolam is a sedative, hypnotic and antidepressant drug widely used in clinics. In this study,the key intermediate （ m ） was synthesized through acetylation and then cyclization in ethanol with uro-tropin from 2 - amino - 3 - （ 2 - chlorobenzoyl） - 5 - ethyhhiophene （ I ） as raw material. The targetproduct etizolam （ V ） was successfully obtained from 111 via sulfuration and cyclization. The total yield ofthe four steps was 56.4%. The improved synthetic process has such advantages as short synthetic route,mild reaction condition, simple operation, high yield and so on.