(1S,3S,5S)-2-氮杂二环[3.1.0]己烷-3-甲酰胺甲烷磺酸盐的合成  

Synthesis of (1S,3S,5S)-2-Azabicyclo[3.1.0]hexane-3 carboxamide hydrochloride

作　　者：朱高峰[1] 张毅[1] 徐黔江[1] 

机构地区：[1]贵阳医学院药学院,贵州贵阳550004

出　　处：《广州化工》2013年第15期62-63,120,共3页GuangZhou Chemical Industry

基　　金：贵州省中药攻关项目黔科合ZY字[2013]3019号

摘　　要：以L-焦谷氨酸为原料经六步反应得到了沙格列汀关键中间体(1S,3S,5S)-2-氮杂二环[3.1.0]己烷-3-甲酰胺甲烷磺酸盐,中间体再与(S)-N-Boc-2-(3-羟基-金刚烷)甘氨酸经缩合,脱水,脱Boc保护得到了目标化合物沙格列汀。本研究着重解决了制约沙格列汀生产成本的合成步骤,即N-Boc-4,5脱氢脯氨酰胺的环丙化反应,形成了一条收率稳定,操作简单,适合工业化生产的反应路线。Commercially available L- pyroglutamic acid as raw materials, （1S, 3S, hexane- 3 -carboxamide methanesulfonie acid salt, the key intermediate of saxagliptin Then the desired compound saxagliptin was synthesized through the two fragments of the key 5S） -2 - azabicyclo [3.1.0] was synthesized via six steps. intermediates and （S） - N - Boc - 3 - hydroxyadamantylglycine via condensation, dehydration, and Boc deprotection. The synthesis steps of constraint to production costs about solved. This formationed saxagliptin also called the cyclopropane of N - Boc - 4, 5 - dehyd - rogenation prolinamide was a reaction route of a stable yield, simple operation, and suitable for industrial production.

关 键 词：合成 环丙化 (1S 3S 5S)-2-氮杂二环[3 1 0]己烷-3-甲酰胺甲烷磺酸盐 沙格列汀 

分 类 号：R914.5[医药卫生—药物化学]