(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

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.