Improvement on Synthesis Process of Apixaban

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.