This paper was focused on the synthesis of new lead compounds with PDE10inhibitors. Starting from2-methyl-6-nitrobenzoic acid, the synthesis of the key intermediate isoindole ketone derivatives has been accomplished via a four-step reaction, including esterification, bromination, cyclization with the amines and reduction in overall yield of46.5%.With2-amino-5-bromobenzoic acid as the starting material, the key intermediate6-benzimidazole substituted quinazoline derivatives2a has been synthesized by sequential cyclization, hydrolysis, esterification, chlorination, nucleophilic, hydrolysis, condensation, and ring closing. The overall yield for the eight steps was1.2%. Analogously,2-amino-3-bromobenzoic acid was allowed to undergo cyclization, hydrolysis, esterification, chlorination, followed by nucleophilic reactions of the key intermediate ketone derivatives of isoindole, hydrolysis, condensation, and cyclizatio to afford the new8-benzimidazole substituted quinazoline derivatives2b in overall yield of2.9%for the eight synthetic steps.The structures of the key intermediates and the title compounds were characterized by1H NMR,13C NMR and MS spectra. |