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 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.