Modular, automated synthesis of spirocyclic tetrahydronaphthyridines from primary alkylamines.

ABSTRACT: Spirocyclic tetrahydronaphthyridines (THNs) are valuable scaffolds for drug discovery campaigns, but access to this 3D chemical space is hampered by a lack of modular and scalable synthetic methods. We hereby report an automated, continuous flow synthesis of α-alkylated and spirocyclic 1,2,3,4-tetrahydro-1,8-naphthyridines ("1,8-THNs"), in addition to their regioisomeric 1,6-THN analogues, from abundant primary amine feedstocks. An annulative disconnection approach based on photoredox-catalysed hydroaminoalkylation (HAA) of halogenated vinylpyridines is sequenced in combination with intramolecular S_NAr N-arylation. To access the remaining 1,7- and 1,5-THN isomers, a photoredox-catalysed HAA step is telescoped with a palladium-catalysed C-N bond formation. Altogether, this provid

SUBMITTER: Cao Q 

PROVIDER: S-EPMC10550966 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature