The First Large-Scale Synthesis of MK-4305: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Disorder

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• 作者：Carl A. Baxter ; Ed Cleator ; Karel M. J. Brands ; John S. Edwards ; Robert A. Reamer ; Faye J. Sheen ; Gavin W. Stewart ; Neil A. Strotman ; Debra J. Wallace
• 刊名：Organic Process Research & Development
• 出版年：2011
• 出版时间：March 18, 2011
• 年：2011
• 卷：15
• 期：2
• 页码：367-375
• 全文大小：959K
• 年卷期：v.15,no.2(March 18, 2011)
• ISSN：1520-586X

文摘

A new synthetic route to drug candidate 1, a potent and selective dual orexin antagonist for the treatment of sleep disorders, has been developed. The key acyclic precursor 10 was prepared in a one-step process in 75% isolated yield from commercially available starting materials using novel chemistry to synthesize 2-substituted benzoxazoles. A reductive amination was followed by a classical resolution to afford chiral diazepane (R)-11. Finally, coupling of (R)-11 with acid 5 furnished the desired drug candidate 1.