Practical Synthesis of a p38 MAP Kinase Inhibitor

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• 作者：Michał ; Achmatowicz ; Oliver R. Thiel ; Philip Wheeler ; Charles Bernard ; Jinkun Huang ; Robert D. Larsen ; Margaret M. Faul
• 刊名：Journal of Organic Chemistry
• 出版年：2009
• 出版时间：January 16, 2009
• 年：2009
• 卷：74
• 期：2
• 页码：795-809
• 全文大小：518K
• 年卷期：v.74,no.2(January 16, 2009)
• ISSN：1520-6904

文摘

p38 MAP kinase inhibitors have attracted considerable interest as potential agents for the treatment of inflammatory diseases. Herein, we describe a concise and efficient synthesis of inhibitor 1 that is based on a phthalazine scaffold. Highlights of our approach include a practical synthesis of a 1,6-disubstituted phthalazine building block 24 as well as the one-pot formation of boronic acid 27. Significant synthetic work to understand the reactivity principles of the intermediates helped in selection of the final synthetic route. Subsequent optimization of the individual steps of the final sequence led to a practical synthesis of 1.