Photoredox Catalysis in a Complex Pharmaceutical Setting: Toward the Preparation of JAK2 Inhibitor LY2784544

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• 作者：James J. Douglas ; Kevin P. Cole ; Corey R. J. Stephenson
• 刊名：Journal of Organic Chemistry
• 出版年：2014
• 出版时间：December 5, 2014
• 年：2014
• 卷：79
• 期：23
• 页码：11631-11643
• 全文大小：688K
• ISSN：1520-6904

文摘

We report a detailed investigation into the application of visible light-mediated photocatalysis to a challenging bond construction in a complex pharmaceutical target. The optimized reaction allowed the direct coupling of N-methylmorpholine with an unfunctionalized pyridazine in good yield and selectivity, and with high purity of the product isolated via crystallization. The reaction also facilitated the expedient synthesis of a range of analogues via the use of other commercially available N-methyl substituted tertiary amines, and therefore it represents an attractive tool for medicinal chemistry. Furthermore, a number of other interesting photoredox reactions were discovered during the course of this investigation, such as a formal methylation reaction via C鈥揘 bond cleavage, functionalization of C鈥揌 bonds alpha to amides, and a visible light-mediated iminium ion reduction.