【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。更多还原

【Abstract】 Commercially available L-pyroglutamic acid as raw materials,(1S,3S,5S)-2-azabicyclo [3.1.0] hexane-3-carboxamide methanesulfonic acid salt,the key intermediate of saxagliptin was synthesized via six steps.Then the desired compound saxagliptin was synthesized through the two fragments of the key intermediates and(S)-N Boc-3-hydroxyadamantylglycine via condensation,dehydration,and Boc deprotection.The synthesis steps of constraint to production costs about saxagliptin also called the cyclopropane of N-Boc-4,5-dehyd-rogenation prolinamide was solved.This formationed a reaction route of a stable yield,simple operation,and suitable for industrial production.更多还原