Asymmetric Fluorination Approach to the Scalable Synthesis of a SYK Inhibitor

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• 作者：Neil R. Curtis ; Suzanne H. Davies ; Matthew Gray ; Stuart G. Leach ; Ross A. McKie ; Lois E. Vernon ; Andrew J. Walkington
• 刊名：Organic Process Research & Development
• 出版年：2015
• 出版时间：July 17, 2015
• 年：2015
• 卷：19
• 期：7
• 页码：865-871
• 全文大小：258K
• ISSN：1520-586X

文摘

A large-scale process for the synthesis of SYK inhibitor 1 has been developed and used to deliver multi-kilogram yields of this active pharmaceutical ingredient. Integral to the scalable process is a combined chiral auxiliary and chiral catalyst mediated diastereoselective fluorination. Safe processes for BH₃路DMS-mediated reduction of ester and amide functions and azide introduction, and a robust Suzuki鈥揗iyaura coupling of a pyrazyl boronate with chloronapthyridine, are described.