阿哌沙班的合成工艺改进

Improvement on Synthesis Process of Apixaban

目的改进阿哌沙班的合成工艺。方法以3-吗啡啉-1-(4-硝基苯基)-5,6-二氢吡啶-2(1H)-酮(2)为起始原料,经缩合,氨化和'一锅法'还原和环合反应,得到阿哌沙班(1)。结果中间体和目标化合物的结构经1H-NMR、13C-NMR、高分辨质谱确证,3步合成总收率为50.2%。结论改进后的工艺适合工业化生产。

OBJECTIVE To improve the synthesis process of apixaban.METHODS Apixaban(1)was synthesized by using 3-morpholino-1-(4-nitrophenyl)-5,6-dihydropyridin-2(1H)-one(2)as the starting material,via condensation,aminolysis and'one-pot'reaction inculding reduction and cyclization.RESULTS The structures of intermediates and target molecule were confirmed by 1H-NMR,13C-NMR and HRMS.The overall yield was 50.2%over 3 steps.CONCLUSION The improved process is suitable for industrial scaling-up.