文摘
Early process development toward a triple reuptake inhibitor is described. Three different routes were evaluated; one of them was optimized and scaled up to generate 470 g of API as this route minimized the formation of undesired side products. The selected route featured Eaton鈥檚 reagent-mediated cyclization of a phenyl acetamide, copper-mediated Buchwald鈥揌artwig coupling to install a morpholine moiety, and palladium-catalyzed 伪-arylation of a dihydroisoquinolinone to construct the core structure.