格列齐特的合成研究

摘要

以1，2-环戊烷二甲酰亚胺为原料，先与80％水合肼反应生成 N-氨基-1，2-环戊烷邻二甲酰亚胺，再经KBH4/ZnCl2在温和条件下还原、成盐得N-氨基-3-氮杂双环[3，3，0]辛烷盐酸盐，最后与对甲苯磺酰脲缩合，经4步反应合成格列齐特，总收率57.7％，产品质量符合中国药典要求。%Using 1 ,2-cyclohexane dicarboximide as starting material,Gliclazide was prepared by four step re-actions.N-Amino-1 ,2-cyclohexane dicarboximide was obtained firstly by reaction of 1 ,2-cyclohexane dicarbox-imide and 80% hydrazine hydrate with good yield,then reduced and formed salt to N-amino-3-azabicyclo[3,3,0] octane monohydrochloride with KBH4/ZnCl2 under mild conditions,eventually Gliclazid was got by condensa-tion of N-amino-3-azabicyclo[3,3,0]octane monohydrochloride and p-toluenesulfonyl urea.The obtained prod-uct of Gliclazide met the requirement of the Pharmacopoeia of the People′s Republic of China (2010 Edition) and its overall yield was 5 7.7%.