利伐沙班降解杂质的合成

目的 为了加强对Xa因子抑制剂类抗凝药利伐沙班原料药的质量控制,合成了利伐沙班的3个降解杂质。方法 利伐沙班(1)经开环反应得到杂质A；杂质A经水解反应得到杂质B；杂质A经取代反应得到杂质C。结果 合成的3种降解杂质的结构经1H-NMR、13C-NMR和MS确证,纯度经HPLC检测均达到97.1%以上。结论 3个杂质可作为利伐沙班原料药质量控制的杂质对照品。

Synthesis of the Degradation Impurity of Rivaroxaban

ABSTRACT: OBJECTIVE In order to perform the quality of rivaroxaban that a kind of anticoagulant drug, three degradation impurities A, B and C were synthesized and characterized. METHODS Rivaroxaban was used as starting material to prepare Impurity A, Impurity B was synthesized by hydrolyzing A, Impurity C was obtained from Impurity A by substitution reaction. RESULTS The structures of the three impurities had been verified by 1H-NMR and 13C-NMR and MS. Their purities were over 97.1% (detected by HPLC). CONCLUSION The synthetic degradation impurities can be used as the reference substance of the impurities in the quality control of rivaroxaban.