bms-663068 and 6-azaindole

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.

Topics: Anti-HIV Agents; Aza Compounds; Cyclic N-Oxides; Halogenation; HIV-1; Humans; Indoles; Molecular Structure; Organophosphates; Piperazines; Prodrugs; Pyrroles; Stereoisomerism; Virus Attachment