The First Large-Scale Synthesis of MK-4305: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Disorder
2011; American Chemical Society; Volume: 15; Issue: 2 Linguagem: Inglês
10.1021/op1002853
ISSN1520-586X
AutoresCarl 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,
Tópico(s)Circadian rhythm and melatonin
ResumoA 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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