Synthesis of novel 3-(quinazol-2-yl)-quinolines via SNAr and aluminum chloride-induced (hetero) arylation reactions and biological evaluation as proteasome inhibitors

I. Boualia (1) , A. Debache (2) , R. Boulcina (2) , Thierry Roisnel (1) , F. Berrée (1) , J. Vidal (1) , B. Carboni (1)

1 ISCR - Institut des Sciences Chimiques de Rennes
2 UMC - Université frères Mentouri Constantine I

A new series of 3-(quinazol-2-yl)-quinolines was synthesized by SNAr reaction from easily prepared 4-chloro-2-(2-chloroquinolin-3-yl)quinazolines and a range of phenols and thiophenol as nucleophiles. The AlCl3-mediated CC bond formation was also successfully exploited to introduce aryl and hereroaryl substituents on one or both heterocyclic units. These procedures afford efficient syntheses of polysubstituted 3-(quinazol-2-yl)-quinolines in few steps and high yields. Some of these polysubstituted 3-(quinazol-2-yl)-quinolines inhibit the human 20S proteasome.

Keywords: AlCl3-mediated reaction; Proteasome inhibitor; Quinazoline; Quinoline; SNAr

Domains: Chemical Sciences; Organic chemistry; Chemical Sciences; Medicinal Chemistry

I. Boualia, A. Debache, R. Boulcina, Thierry Roisnel, F. Berrée, et al.. Synthesis of novel 3-(quinazol-2-yl)-quinolines via SNAr and aluminum chloride-induced (hetero) arylation reactions and biological evaluation as proteasome inhibitors. Tetrahedron Letters, 2020, 61 (17), pp.151805. ⟨10.1016/j.tetlet.2020.151805⟩. ⟨hal-02569954⟩