The First Large-Scale Synthesis of MK-4305: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Disorder
Organic Process Research & Development2011Vol. 15(2), pp. 367–375
Citations Over TimeTop 10% of 2011 papers
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
Abstract
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.
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