Development of a Practical and Scalable Synthesis of a Potent p38 Mitogen-Activated Protein Kinase Inhibitor

详细信息    查看全文

• 作者：Shinya Yoshida ; Yasumasa Hayashi ; Kazuyoshi Obitsu ; Atsushi Nakamura ; Takashi Kikuchi ; Tatsuya Sawada ; Takenori Kimura ; Takumi Takahashi ; Takashi Mukuta
• 刊名：Organic Process Research & Development
• 出版年：2012
• 出版时间：November 16, 2012
• 年：2012
• 卷：16
• 期：11
• 页码：1818-1826
• 全文大小：362K
• 年卷期：v.16,no.11(November 16, 2012)
• ISSN：1520-586X

文摘

Process research and development of a practical and scalable synthetic method toward a potent inhibitor of p38 mitogen-activated protein kinase 1 is described. The medicinal chemistry synthetic method had several issues in scale-up synthesis. In contrast, the synthetic method described here does not require purification by column chromatography for all steps, and the formation of impurities is suppressed well. Aminopyrazole ring formation was achieved by reaction between a new chiral amine building block 7 and bromoketone unit 4 as a key reaction. This highly efficient and scalable process was successfully demonstrated in the large-scale synthesis of 1路HBr.