吡仑帕奈关键中间体有关物质研究  

Study on related substances of the key intermediate of perampanel

作　　者：刘旭岩 仇永富 王维维 陈忻栋 倪峰 王冠[1,2] LIU Xu-yan;QIU Yong-fu;WANG Wei-wei;CHEN Xin-dong;NI Feng;WANG Guan(Novel Technology Center of Pharmaceutical Chemistry,Shanghai Institute of Pharmaceutical Industry Co.,Ltd.,China State Institute of Pharmaceutical Industry Co.,Ltd.,Shanghai 201203,China;Shanghai Engineering Research Center of Pharmaceutical Process,Shanghai 201203,China;Shanghai Shyndec Pharmaceutical Co.,Ltd.,Shanghai 201203,China)

机构地区：[1]中国医药工业研究总院有限公司上海医药工业研究院有限公司化学制药新技术中心,上海201203 [2]上海药物合成工艺过程工程技术研究中心,上海201203 [3]上海现代制药股份有限公司,上海201203

出　　处：《中国药物化学杂志》2023年第9期665-670,共6页Chinese Journal of Medicinal Chemistry

摘　　要：目的研究吡仑帕奈关键中间体5-(2-吡啶基)-1,2-二氢吡啶-2-酮(4)有关物质的来源与合成方法,为其质量控制提供依据并为其质量研究提供有关物质的对照品。方法根据已报道的吡仑帕奈的合成工艺路线,分析关键中间体4的生产过程中可能存在的有关物质并进行定向合成;采用高效液相-紫外检测色谱法建立中间体4及其有关物质的分析方法。结果与结论发现关键中间体4生产过程中可能存在的7个有关物质(A~G),并定向合成其中5个有关物质(B、D~G),其结构均经^(1)H-NMR、^(13)C-NMR和ESI-MS谱确证,初步建立了吡仑帕奈关键中间体4及其有关物质的高效液相色谱分析方法。本研究为吡仑帕奈关键中间体4及吡仑帕奈原料药的质量控制提供一定的参考。5-(2-Pyridyl)-1,2-dihydropyridine-2-one(4)is the key intermediate of antiepileptic drug perampanel.In this study,seven related substances of the key intermediate 4 of perampanel were researched and five related substances(B,D-G)were directionally synthesized.Using 2-methoxypyridine as the raw material,the related substances B,D,F and G were prepared.The related substance E was prepared from 2-methoxy-3-bromopyridine.The structures of synthesized related substances were confirmed by^(1)H-NMR,^(13)C-NMR and ESI-MS.Moreover,the analytical methods of the key intermediate 4 and seven related substances were established by HPLC,and the results were reasonable.These researches strengthen the quality control of the key intermediate 4 and provide reference for perampanel′s quality research.

关 键 词：吡仑帕奈 有关物质 合成 分析方法 

分 类 号：R914[医药卫生—药物化学]