title: Synthesis of the 6-azaindole containing HIV-1 attachment inhibitor pro-drug, BMS-663068.
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.
authors.affiliation: Chemical Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: Christina
authors.initials: C
authors.lastname: Risatti
authors.forename: Michael
authors.initials: M
authors.lastname: Bultman
authors.forename: Maxime
authors.initials: M
authors.lastname: Soumeillant
authors.forename: James
authors.initials: J
authors.lastname: Simpson
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.forename: Dayne
authors.initials: D
authors.lastname: Fanfair
authors.forename: Michelle
authors.initials: M
authors.lastname: Mahoney
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Mudryk
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Fox
authors.forename: Yi
authors.initials: Y
authors.lastname: Hsaio
authors.forename: Saravanababu
authors.initials: S
authors.lastname: Murugesan
authors.forename: David A
authors.initials: DA
authors.lastname: Conlon
authors.forename: Frederic G
authors.initials: FG
authors.lastname: Buono
authors.forename: Martin D
authors.initials: MD
authors.lastname: Eastgate
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects; D054879:Halogenation; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010755:Organophosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011355:Prodrugs; D011758:Pyrroles / Q000737:chemistry; D013237:Stereoisomerism; D053585:Virus Attachment / Q000187:drug effects*
chemical_list: C504762:6-azaindole; D019380:Anti-HIV Agents; D001372:Aza Compounds; D003497:Cyclic N-Oxides; D007211:Indoles; D010755:Organophosphates; D010879:Piperazines; D011355:Prodrugs; D011758:Pyrroles; C576364:fostemsavir