Asymmetric Fluorination Approach to the Scalable Synthesis of a SYK Inhibitor

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 proces...

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Bibliographic Details
Published inOrganic process research & development Vol. 19; no. 7; pp. 865 - 871
Main Authors Curtis, Neil R, Davies, Suzanne H, Gray, Matthew, Leach, Stuart G, McKie, Ross A, Vernon, Lois E, Walkington, Andrew J
Format Journal Article
LanguageEnglish
Published American Chemical Society 17.07.2015
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Summary: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·DMS-mediated reduction of ester and amide functions and azide introduction, and a robust Suzuki–Miyaura coupling of a pyrazyl boronate with chloro­napthyridine, are described.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.5b00131