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

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 chemistr...

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Bibliographic Details
Published in:Organic process research & development 2011-03, Vol.15 (2), p.367-375
Main Authors: Baxter, Carl A, Cleator, Ed, Brands, Karel M. J, Edwards, John S, Reamer, Robert A, Sheen, Faye J, Stewart, Gavin W, Strotman, Neil A, Wallace, Debra J
Format: Article
Language:English
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Summary: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.
ISSN:1083-6160
1520-586X
DOI:10.1021/op1002853