盐酸瑞芬太尼有关物质的合成  

Syntheses of related substances of remifentanil hydrochloride

作　　者：李丽平 张肖杰 杜超宇 何凤 苗庆柱 LI Li-ping;ZHANG Xiao-jie;DU Chao-yu;HE Feng;MIAO Qing-zhu(Hebei Pharmaceutical professional inspector Corpshijiazhuang 050000 China;Sinopharm Group Industrial Co.,Ld.,Bejing 101300,China)

机构地区：[1]河北省药品职业化检查员总队,河北石家庄050000 [2]国药集团工业有限公司,北京101300

出　　处：《中国药物化学杂志》2022年第7期518-521,共4页Chinese Journal of Medicinal Chemistry

摘　　要：目的 合成盐酸瑞芬太尼原料药的有关物质,为其质量研究提供参照物。方法 以瑞芬太尼的中间体1-苄基-4-(苯基氨基)哌啶-4-羧酸甲酯(6)为原料,经酰化反应、氢化反应及加成反应,合成盐酸瑞芬太尼的有关物质1-(3-甲氧基-3-氧丙基)-4-(N-苯基乙酰胺基)哌啶-4-羧酸甲酯(有关物质B)、1-(3-甲氧基-3-氧丙基)-4-(N-苯基丁酰胺基)哌啶-4-羧酸甲酯(有关物质D);以瑞芬太尼为原料,经碱性水解,合成盐酸瑞芬太尼有关物质3-(4-(甲氧基羰基)-4-(N-苯基丙酰胺基)哌啶-1-基)丙酸(有关物质C)。结果与结论合成了盐酸瑞芬太尼3种有关物质,并详细描述了其实验步骤及其关键控制参数,有关物质B、C、D的结构经^(1)H-NMR,^(13)C-NMR和ESI-MS谱确证。Three related substances of remifentanil hydrochloride were synthesized, namely methyl-4-[acetyl(phenyl)amino]-1-(3-methoxy-3-oxopropyl)piperidine-4-carboxylate(related substance B);3-(4-(methoxycarbonyl)-4-(phenyl(propanoyl)amino]-piperidin-1-yl]propanoic acid(related substance C);methyl-4-[butanoyl(phenyl)amino]-1-(3-methoxy-3-oxopropyl)piperidine-4-carboxylate(related substance D),and detailed description of its experimental procedures and key control parameters.The syntheses of these compounds are of great significance to control the quality research standards of remifentanil hydrochloride, and the structures have been confirmed by ^(1)H-NMR,^(13)C-NMR and ESI-MS.

关 键 词：盐酸瑞芬太尼 有关物质 合成 结构确证 

分 类 号：R914[医药卫生—药物化学]