米格列奈钙的合成新工艺  

New synthetic process of mitiglinide calcium

作　　者：王江霞[1] 王盼[1] 齐珊[2] 刘立云[2] 尚振华[1] 

机构地区：[1]河北科技大学化学与制药工程学院,石家庄050018 [2]石药集团,石家庄050000

出　　处：《中国新药杂志》2014年第10期1201-1203,1209,共4页Chinese Journal of New Drugs

摘　　要：目的:对目前米格列奈钙的合成路线进行优化,以获得可用于工业生产的工艺路线。方法:以(S)-2-苄基丁二酸和CDI为起始原料,制得活性酰胺后与顺式全氢异吲哚盐酸盐反应,再与氯化苄成酯后进行提纯精制,脱苄基后钙化成盐得到米格列奈钙。结果:所得米格列奈钙经HPLC检测纯度达到99.88%以上,总收率为24.46%。结论:该合成路线操作简单,收率较高,产品纯度高,适合工业化生产。Objective： To optimize the current synthesis routes for developing a new synthetic route for mitiglinide calcium production. Methods：（S）-2-benzylsuccinic acid and CDI were used as the starting materials to get the active amide. Then the active amide was reacted with the hydrochloride salt of cis-hexahydroisoindoline and benzyl chloride to get purified benzyl ester; thereafter,debenzylation and calcification were done to get mitiglinide calcium. Results： Mitiglinide calcium was synthesized with a total yield of 24. 46%,and the purity was 99. 88% determined by HPLC. Conclusion： This synthetic process is easy to operate with high yield and purity, and suitable for industrial production.

关 键 词：米格列奈钙 (S)-2-苄基丁二酸 抗糖尿病药物 合成 

分 类 号：R914.5[医药卫生—药物化学]