Pilot-Plant Preparation of 3,4-Dihydropyridin-2-one Derivatives, the Core Structures of P2X7 Receptor Antagonists

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• 作者：Xiaojun Huang ; Scott Broadbent ; Charles Dvorak ; Shu-Hai Zhao
• 刊名：Organic Process Research & Development
• 出版年：2010
• 出版时间：May 21, 2010
• 年：2010
• 卷：14
• 期：3
• 页码：612-616
• 全文大小：160K
• 年卷期：v.14,no.3(May 21, 2010)
• ISSN：1520-586X

文摘

The pilot-plant syntheses of 3 and 4, the core structures of a series of P2X₇ antagonists are described. The sole stereogenic center in the dihydropyridinone ring was generated by catalytic desymmetrization. Selective formylation, followed by a tandem imination/lactamization sequence, produced the 3,4-dihydropyridin-2-one ring. The compounds 3 and 4 were produced at multikilogram scale in good overall yield (22% over six steps) and excellent stereochemical purity (97% ee for 3, 100% ee for 4).