2015•Organic Process Research & DevelopmentRequires access
Development of an Efficient Synthesis of (2-Aminopyrimidin-5-yl) Boronic Acid
Nitinchandra D. Patel, Yongda Zhang, Joe Gao, Kanwar Sidhu, Jon C. Lorenz, Keith R. Fandrick, Jason A. Mulder, Melissa A. Herbage, Zhibin Li, Shengli Ma, Heewon Lee, Nelu Grinberg, Jinhua J. Song, Carl A. Busacca, Nathan K. Yee, Chris H. Senanayake
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Abstract
A practical and cost-effective synthesis of (2-aminopyrimidin-5-yl) boronic acid 1b has been developed. Key features of the synthesis include the inexpensive in situ protection of the amine via bis-silylation using TMSCl followed by metal–halogen exchange using n -BuLi and trapping with B(O i -Pr) 3 . The water-soluble boronic acid is isolated by a well-designed acid–base sequence providing the target in 80% yield and high purity for the two-step process. The large-scale (15 kg) implementation of a Suzuki–Miyaura borylation to form the pinacol boronic ester is also described.