Wu, Bin, Zhang, Sisi, Hong, Tao, Zhou, Yizong, Wang, Hui, Shi, Min, Yang, Hongwei, Tian, Xiangguang, Guo, Jing, Bian, Jianwei, Roache, James, Delgado, Pete, Mo, Ruowei, Fridrich, Cary, Gao, Feng and Wang, Joseph (2020) Development of a Practical Synthesis of an FXI (Factor XI) Inhibitor. Organic process research & development, 24 (11). pp. 2780-2788.

Abstract

The scalable synthesis of an FXI (Factor XI) inhibitor 12 employing multiple emerging technologies is described. The reduction of ketone to chiral alcohol was established through a biocatalysis approach. The Suzuki-Miyaura cross coupling reaction was facilitated by surfactant chemistry. A harsh hydrolysis of the nitrile was performed in a continuous manufacturing mode. Extensive reaction optimization and process development led to a well-controlled protocol for scale-up. The alternative approach described here addressed issues from the discovery route and was utilized to deliver the desired target for preclinical studies.

Item Type:	Article
Keywords:	FXI inhibitor, biocatalysis, continuous manufacturing, surfactant, scale-up
Date Deposited:	10 Dec 2020 00:45
Last Modified:	10 Dec 2020 00:45
URI:	https://oak.novartis.com/id/eprint/43123