多替拉韦钠系列开环物质的合成

Synthesis of ring opening compounds from the dolutegravir sodium series

本文报道了两个多替拉韦钠开环杂质合成的新方法。以甲基多替拉韦(多替拉韦钠中间体)为起始原料,在溴化钠催化条件下,使用三甲基氯硅烷进行开环,再经氯化镁脱甲基得到多替拉韦钠开环杂质。所合成的杂质都经过核磁和质谱的表征。该方法可快速、高效地制备出多替拉韦钠开环杂质及其衍生杂质,为多替拉韦钠中间体和原料药的质量研究提供技术支持。

A new method for the synthesis of two ring opening impurities of dolutegravir sodium were reported in this paper.The ring opening impurities of dolutegravir sodium were obtained with methyl dolutegravir(a intermediate of dolutegravir sodium)as a starting material,by using sodium bromide as catalyzer and trimethylchlorosilane as ring-opening reagent,and demethylated reaction mediated by magnesium chloride.The structures of the above compounds were characterized by NMR and mass spectrometry.This method could quickly and efficiently prepare ring opening impurities and their derivative impurities of dolutegravir sodium,and provide technical support for the quality research of dolutegravir sodium intermediates and active pharmaceutical ingredient.