New synthetic process of apixaban

Objective: To develop a new synthetic route for apixaban by optimizing the reported synthesis routes. Methods: Nitro-compound 6 was used as starting material and it was subjected to the reactions of iron reduction,acylation,cyclization and hydrolysis to generate apixaban acid 2. Apixaban acid 2 was reacted with CDI to afford an active amide,followed by aminolysis with aqueous ammonia to produce the target compound apixaban.Results: Apixaban was synthesized with a total yield of 67. 2%,and the purity was > 99. 88% as determined by HPLC. Conclusion: This route has overcome the shortcomings of the reported synthesis methods for apixaban,such as the expensive materials,harsh and not easy to be monitored reaction conditions,low yield,et al. In this paper,a significantly improved strategy has been developed to meet the requirement for industrial production,with the advantages of low production cost,simple operation,mild reaction conditions,high process stability,and high purity of the target product,et al.