Abstract
The development of a short and efficient synthesis of a complex 6-azaindole, BMS-663068, is described. Construction of the 6-azaindole core is quickly accomplished starting from a simple pyrrole, via a regioselective Friedel-Crafts acylation, Pictet-Spengler cyclization, and a radical-mediated aromatization. The synthesis leverages an unusual heterocyclic N-oxide α-bromination to functionalize a critical C-H bond, enabling a highly regioselective copper-mediated Ullmann-Goldberg-Buchwald coupling to install a challenging triazole substituent. This strategy resulted in an efficient 11 step linear synthesis of this complex clinical candidate.
MeSH terms
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / pharmacology*
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Aza Compounds / chemical synthesis*
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Aza Compounds / chemistry
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Aza Compounds / pharmacology*
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Cyclic N-Oxides / chemistry
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HIV-1 / drug effects
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Halogenation
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Humans
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology*
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Molecular Structure
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Organophosphates / chemical synthesis*
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Organophosphates / chemistry
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Organophosphates / pharmacology*
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology*
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Prodrugs
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Pyrroles / chemistry
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Stereoisomerism
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Virus Attachment / drug effects*
Substances
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6-azaindole
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Anti-HIV Agents
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Aza Compounds
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Cyclic N-Oxides
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Indoles
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Organophosphates
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Piperazines
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Prodrugs
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Pyrroles
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fostemsavir