Study on Preparation Process of Anticoagulant BAY2433334

Objective: To develop a synthetic process route and method more suitable for industrialscale-up production of FXIa inhibitor BAY2433334 (asundexian). Method: BAY2433334 is obtained from (2R)-2-aminobutyric acid by esterification, diazotization, condensation reaction, deacetyl deprotection, activation reaction, and Mitsunobu reaction. Results: The target compound BAY2433334 was synthesized by the above method is simple to operate, and the raw materials are inexpensive and readily available. Simultaneously, the product quality is very high: Few O-alkylated impurities are generated during the reaction, with a high N-alkylated product/O-alkylated product ratio (above 35-45:1). Meanwhile, the ee value is greater than 99%, which means that there are very few isomers present. As a result，no chiral resolution is required, which greatly reduces the cost. Conclusion: A new process route suitable for the industrial production of BAY2433334 has been developed in this paper, which avoids the patent limitations of the originator company of BAY2433334 to the preparation of BAY2433334, improves the product quality of BAY2433334, and reduces the production cost of BAY2433334.