2种雷美替胺杂质的制备与结构确证

Preparation and structural confirmation of two Ramelteon impurities

目的为推动雷美替胺药品质量标准的提高,制备了雷美替胺的2种杂质。方法将雷美替胺原料进行高温破坏,产生目标杂质,再通过制备色谱和萃取,分离纯化得到纯度较高的目标杂质。分别用MS、1H NMR、13 C NMR对杂质进行结构确证。结果结构确证结果表明,分离纯化得到的2种杂质与(S)-N-[2-(6-氧代-1,6,7,8-四氢-2H-茚并[5,4-b]呋喃-8-基)-乙基]-丙酰胺(杂质Ⅰ)、(S)-N-[2-(7,8-二氢-6H-茚并[5,4-b]呋喃-8-基)-乙基]-丙酰胺(杂质Ⅱ)的结构相符。结论分离纯化得到的2种杂质,具有较高的纯度,可以作为雷美替胺质量研究的对照物。

Objective To prepare two ramelteon impurities in order to improve the quality standard of ramelteon.Methods Rametimine was destroyed to obtain the target impurities at high temperature,and then the target impurities with high purity could be obtained by preparative chromatography and extraction.The structures of the two impurities were confirmed by MS,1H NMR and 13 C NMR.Results The data of structural confirmation showed that the two impurities obtained by separation and purification were consistent with the structure of(S)-N-[2-(6-Oxo-1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-yl)-ethyl]-propanamide(impurity Ⅰ)and(S)-N-[2-(7,8-Dihydro-6H-indeno[5,4-b]furan-8-yl)-ethyl]-pro-panamide(impurity Ⅱ).Conclusion The two impurities obtained by separation and purification have high purity,which can be used for conference of ramelteon quality control.