雷美替胺降解杂质的制备  

Preparation of the Degradation Impurities of Ramelteon

作　　者：张杰[1] 李国贤[1] 乔萍[1] 梁文[1] 薛涛[1] ZHANG Jie LI Guoxian QIAO Ping LIANG Wen XUE Tao(Yangtze River Pharmaceutical Group Co., Ltd., Taizhou 22530)

机构地区：[1]扬子江药业集团有限公司,江苏泰州225300

出　　处：《中国医药工业杂志》2017年第6期833-836,共4页Chinese Journal of Pharmaceuticals

摘　　要：为了更好地控制雷美替胺的质量,设计并合成了雷美替胺的3种降解杂质。分别为(S)-N-[2-(4-羟基-2,6,7,8-四氢-1H-茚并[5,4-b]呋喃-8-基)乙基]丙酰胺(IP1)、2-羟基-N-[2-[(S)-2,6,7,8-四氢-1H-茚并[5,4-b]呋喃-8-基]乙基]丙酰胺(IP2)和N-[2-(2,6-二氢-1H-茚并[5,4-b]呋喃-8-基)乙基]丙酰胺(IP3),所得产物经~1HNMR、^(13)CNMR和HRMS确证结构。破坏性试验证明,酸性条件主要产生杂质IP1与IP3,氧化条件下主要产生杂质IP2。To perform the quality control of ramelteon, three degradation impurities were synthesized under acidic, alkaline and oxidation conditions. The strutures of these three degradation impurities： （S）-N-[2-（4-hydroxy-2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-yl）ethyl]propionamide （IP1）, 2-hydroxy-N-[2-[（S）-2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-yl]ethyl]propionamide （IP2）, and N-[2-（2,6-dihydro-1H-indeno[5,4-b]furan-8-yl）ethyl]propionamide （IP3） were confirmed by 1H NMR, 13C NMR and HRMS. The results of destructive tests showed that, IP1 and IP3 were generated under acidic conditions and IP2 was generated under oxidation condition.

关 键 词：雷美替胺 降解杂质 合成工艺 镇静催眠药 

分 类 号：R971.3[医药卫生—药品]