Coupling-Condensation Strategy for the Convergent Synthesis of an Imidazole-Fused 2-Aminoquinoline NLRP3 Agonist.

Autor:	Bi C; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Chadwick J; Chemical Process Development, Bristol Myers Squibb, Reeds Lane, Moreton, Wirral CH46 1QW, U.K., Davies ML; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., DelMonte AJ; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Geng P; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Glace AW; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Green RA; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Gurak JA Jr; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Haley MW; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., He BL; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Inankur B; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Jamison CR; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Joe CL; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Kolotuchin S; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Lin D; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Lou S; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Nye J; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Ortiz A; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Purdum GE; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Rosso VW; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Shah M; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Simmons EM; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Stevens JM; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Strotman NA; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Tan Y; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States., Zhang L; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
Jazyk:	angličtina
Zdroj:	The Journal of organic chemistry [J Org Chem] 2023 Jan 06; Vol. 88 (1), pp. 384-394. Date of Electronic Publication: 2022 Dec 14.
DOI:	10.1021/acs.joc.2c02395
Abstrakt:	The development of a convergent route to the NLRP3 (nucleotide-binding domain and leucine-rich repeat-containing protein 3) agonist BMS-986299 is reported. The synthesis relies on a key Miyaura borylation and a tandem Suzuki-Miyaura coupling between an iodoimidazole and an o -aminochloroarene, followed by acid-mediated cyclization to afford the aminoquinoline core. The subsequent Boc cleavage and regioselective acylation afford the target compound. Two routes to the iodoimidazole intermediate are presented, along with the synthesis of the o -aminochloroarene via Negishi coupling. The convergent six-step route leads to an 80% reduction in process mass intensity compared to the linear enabling synthesis.
Databáze:	MEDLINE
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