Merging Biocatalysis, Flow, and Surfactant Chemistry: Innovative Synthesis of an FXI (Factor XI) Inhibitor,Organic Process Research & Development

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Merging Biocatalysis, Flow, and Surfactant Chemistry: Innovative Synthesis of an FXI (Factor XI) Inhibitor
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2020-11-09 , DOI: 10.1021/acs.oprd.0c00412
Bin Wu ₁ , Sisi Zhang ₁ , Tao Hong ₁ , Yizong Zhou ₁ , Hui Wang ₁ , Min Shi ₁ , Hongwei Yang ₁ , Xiangguang Tian ₁ , Jing Guo ₁ , Jianwei Bian ₁ , James Roache ₂ , Pete Delgado ₂ , Ruowei Mo ₂ , Cary Fridrich ₂ , Feng Gao ₁ , Jianhua Wang ₁

Affiliation

The scalable synthesis of an FXI (Factor XI) inhibitor 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.

中文翻译：

融合生物催化，流动和表面活性剂化学：FXI（因子XI）抑制剂的创新合成

描述了采用多种新兴技术的FXI（Factor XI）抑制剂的可扩展合成。通过生物催化方法确定了将酮还原为手性醇。表面活性剂化学促进了铃木-宫浦的交叉偶联反应。以连续制造模式进行腈的剧烈水解。广泛的反应优化和工艺开发导致了良好控制的放大方案。此处介绍的替代方法解决了发现路线中的问题，并用于为临床前研究提供所需的靶标。

更新日期：2020-11-21

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