利伐沙班降解杂质的合成

Synthesis of the Degradation Impurity of Rivaroxaban

目的合成利伐沙班的3个降解杂质,从而加强对Xa因子抑制剂类抗凝药利伐沙班原料药的质量控制。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、^(13)C-NMR和MS确证,纯度经HPLC检测均>99.0%。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。

OBJECTIVE To perform the quality of rivaroxaban which was a kind of anticoagulant drug, three degradation impurities A, B and C were synthesized and characterized. METHODS Rivaroxaban （1 ） was used as starting material to prepare Impurity A , impurity B was synthesized by hydrolyzing impurity A , and impurity C was obtained from impurity A by substitution reaction. RESULTS The structures of the three impurities had been verified by 1^H-NMR and 13^C-NMR and MS. Their purities were over 99.0% （detected by HPLC）. CONCLUSION The synthetic degradation impurities can be used as the reference substance of the impurities in the quality control of rivaroxaban.