Development of a Scalable Synthesis of an Azaindolyl-Pyrimidine Inhibitor of Influenza Virus Replication

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• 作者：Jianglin Liang ; John E. Cochran ; Warren A. Dorsch ; Ioana Davies ; Michael P. Clark
• 刊名：Organic Process Research & Development
• 出版年：2016
• 出版时间：May 20, 2016
• 年：2016
• 卷：20
• 期：5
• 页码：965-969
• 全文大小：282K
• 年卷期：0
• ISSN：1520-586X

文摘

A scalable, asymmetric route for the synthesis of the influenza virus replication inhibitor 2 is presented. The key steps include an enzymatic desymmetrization of cis-1,3-cyclohexanediester in 99% yield and 96% ee, S_NAr displacement of a methanesulfinylpyrimidine, and a Curtius rearrangement to form a morpholinyl urea. This high-yielding route allowed us to rapidly synthesize hundreds of grams of 2 in 99% purity to support in vivo studies.