咪达唑仑关键中间体的新合成工艺  

The new synthetic process for key intermediates of midazolam

作　　者：陆一菱 赖海燕[1] 陆宏龙 李茜[1] 安然 Lu Yiling;Lai Haiyan;Lu Honglong;Li Qian;An Ran(Department of Pharmacy,the Third People's Hospital of Chengdu,Chengdu 610031;Guangxi Medical College,Nanning 530023)

机构地区：[1]成都市第三人民医院药学部,成都610031 [2]广西卫生职业技术学院,南宁530023

出　　处：《中国抗生素杂志》2025年第2期200-204,共5页Chinese Journal of Antibiotics

摘　　要：目的 咪达唑仑关键中间体F的合成工艺研究。方法 以7-氯-5-(2-氟苯基)-1,3-二氢-2H-1,4-苯并二氮杂[艹卓]-2-酮(化合物A)为原料,经缩合、取代、还原、环合等多步反应制备咪达唑仑关键中间体F。结果 新合成工艺制备中间体F的总收率为37%。结论 新工艺具有反应条件相对温和、操作简便等特点,不仅避免超低温反应、高危险性催化氢化反应,而且避免亚硝胺杂质的引入,具有工业化放大的潜力。Objective To study the synthetic route to key intermediates of midazolam.Methods 7-Chloro-5-(2-fluoro-phenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one(Compound A)was used as the starting material to synthesize the key intermediate F of midazolam via multi-step reactions,including condensation,substitution reaction,reduction,and cyclization reaction.Results The key intermediate F of midazolam was obtained at a 37%overall yield with the new synthetic route.Conclusion The newly developed synthetic process has many advantages,such as mild reaction conditions,simple operation,being free of ultra-low temperature,high-risk catalytic hydrogenation,and avoiding the production of nitrosamine impurities,which was suitable for industrial production.

关 键 词：咪达唑仑中间体 合成工艺研究 亚硝胺杂质 工业化潜力 

分 类 号：R9[医药卫生—药学]