Development of an Efficient Synthesis of (2-Aminopyrimidin-5-yl) Boronic Acid

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• 作者：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
• 刊名：Organic Process Research & Development
• 出版年：2016
• 出版时间：January 15, 2016
• 年：2016
• 卷：20
• 期：1
• 页码：95-99
• 全文大小：270K
• ISSN：1520-586X

文摘

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(Oi-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.