卡培他滨杂质的合成

Synthesis of Capecitabine Impurity

合成美国药典中卡培他滨的3种主要杂质(杂质A、B、C)。1,2,3-三乙酰氧基-5-脱氧-D-核糖(1)与硅醚化的5-氟胞嘧啶(5-FC)经过缩合、水解反应得到杂质A,(1)与硅醚化的5-氟尿嘧啶(5-FU)经过缩合、水解反应得到杂质B,卡培他滨(4)与N,N'-羰基二咪唑(CDI)经过关环反应得到杂质C。杂质A、B、C的结构经1H-NMR、13C NMR和MS确认。杂质A、B、C可作为卡培他滨质量研究的杂质对照品。

Three impurities （impurity A, B, C） recorded in united states pharmacopeia were synthesized in capecitabine. Impurity A was synthesized from 1.2.3 ＂- 0 - triacetyl - 5 ＂- deoxy - D - ribomranose （ 1 ） and hexamethyl disilylamine 5 - fluomcytosine（5 -FC） by condensation and hydrolysis. Impurity B was synthesized from （1） and hexamethyl disilylamine 5 - fluomcytosine（5- FU） by condensation and hydrolysis. Impurity C was obtained by the ring- closure reaction of eapecitabine （4） with N,N＇-carbonyldiimidazole（CDI）. The structures of three impurities were verified by ^1 H- NMR ,^13C- NMR and MS and can be used as the reference substance of the impurities in the quality control of eapecitabine.