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阿哌沙班中3个杂质的合成研究 被引量:4

Synthesis of three impurities in apixaban
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摘要 目的设计并合成阿哌沙班中的3个杂质。方法以2-氯-2-[2-(4-甲氧基苯基)亚肼基]乙酸乙酯和5,6-二氢-3-(4-吗啉基)-1-[4-(2-氧代-1-哌啶基)苯基]-2(1H)-吡啶酮为起始原料,经过环合和水解反应得到目标化合物1,化合物1分别经过水解和取代反应得到目标化合物2和3。结果合成了目标化合物,并利用MS、^1H-NMR和^13C-NMR确证了结构:目标化合物1~3的质量分数分别为99.3%、99.1%、99.2%。结论 3个杂质的合成和纯化为阿哌沙班的杂质研究奠定了物质基础。 Objective To design and synthesize three impurities in apixaban. Methods 2-Chloro-2-[2-(4-methoxyphenyl) hydrazono]acetate and 5,6-dihydro-3-(4-morpholinyl)-1-[4-(2-oxo-1-piperidinyl)phenyl]-2(1H)-pyridinone were used as starting materials to synthesize the target compound 1 by cyclization and hydrolysis reactions, and compound 1 was used to synthesize the target compound 2 and compound 3 by hydrolysis and substitution reactions. Results The target compounds were synthesized and characterized by MS, ^1H-NMR, and ^13C-NMR method. And the purity detected were 99.3%, 99.1%, and 99.2%, respectively. Conclusion The synthesis and purification of three impurities lay the material base for the study of impurities in apixaban.
作者 范巧云 高立国 韩学文 穆帅 王以富 梁兴运 张晓军 闫少杰 FAN Qiao-yun,GAO Li-guo,HAN Xue-wen,MU Shuai,WANG Yi-fu,LIANG Xing-yun,ZHANG Xiao-jun,YAN Shao-jie (1. Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China; 2. Tianjin Haiguang Pharmaceutical Co., Ltd., Tianjin 300457, China; 3. Shool of Pharmacy, Henan University, Kaifeng 475000, China)
出处 《现代药物与临床》 CAS 2016年第8期1125-1128,共4页
关键词 阿哌沙班 杂质 2-氯-2-[2-(4-甲氧基苯基)亚肼基]乙酸乙酯 5 6-二氢-3-(4-吗啉基)-1-[4-(2-氧代-1-哌啶基)苯基]-2(1H)-吡啶酮 apixaban impurity 2-chloro-2-[2-(4-methoxyphenyl) hydrazono]acetate 5 6-dihydro-3-(4-morpholinyl)-1-[4-(2-oxo 1-piperidinyl)phenyl]-2(1H)-pyridinone
作者简介 范巧云(1982-),女,江苏徐州人,助理研究员,主要从事化学药物的开发及工艺研究。Tel:(022)23003587 E-mail:fanqy@tjipr.com 通信作者:穆帅,助理研究员。E-mail:mus@tjipr.com 通信作者:王以富,副研究员。E-mail:wymy@163.com
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