质子泵抑制剂泮托拉唑杂质的合成  

Synthesis of the impurities of proton pump inhibitor pantoprazole

作　　者：张彪 李雪[2] 高艺 邬淋 刘晓平[2] 胡春[2] ZHANG Biao;LI Xue;GAO Yi;WU Lin;LIU Xiaoping;HU Chun(Forensic Center of Public Security of Jinzhou,Jinzhou 121000,China;Key Laboratory of Structure-Based Drug Design and Discovery(Shenyang Pharmaceutical University),Ministry of Education,Shenyang 110016,China)

机构地区：[1]锦州市公安司法鉴定中心,辽宁锦州121000 [2]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《中国药物化学杂志》2024年第6期455-459,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家重大新药创制科技重大专项(2009ZX09301-012)。

摘　　要：目的合成泮托拉唑杂质,为其质量控制提供标准对照品。方法以5-(二氟甲氧基)-2-巯基-1H-苯并咪唑和2-氯甲基-3,4-二甲氧基吡啶盐酸盐为原料,经缩合、氧化等反应合成泮托拉唑杂质。结果依据化合物基团反应性的差异,采取不同合成方法制备了4种泮托拉唑杂质,分别为化合物1(泮托拉唑硫醚)、化合物2(泮托拉唑砜)、化合物3(泮托拉唑砜-N-氧化物)和化合物4(泮托拉唑-N-氧化物),其化学结构均经红外光谱、质谱和核磁共振氢谱确证。结论制备的4种泮托拉唑杂质可作为泮托拉唑质量控制的标准对照品,其合成反应条件温和、原料易得、操作简单、收率高、纯度高。In order to strengthen the quality control of pantoprazole products,four impurities of pantoprazole,i.e.compound 1(pantoprazole sulfide),compound 2(pantoprazole sulfone),compound 3(pantoprazole sulfone-N-oxide)and compound 4(pantoprazole N-oxide),were synthesized through a series of chemical transformations including condensation,oxidation starting from 5-difluoromethoxy-2-mercapto-^(1)H-benzimidazole and 2-chloromethyl-3,4-dimethoxypyridine hydrochloride.The structures of target compounds were characterized by IR,MS and ^(1)H-NMR.These four pantoprazole impurities can be used as standard reference for quality control of pantoprazole.

关 键 词：质子泵抑制剂 泮托拉唑 杂质 合成 

分 类 号：R914[医药卫生—药物化学]