Brexpiprazole – an anti-psychotic drug approved for the treatment of schizophrenia – has beensynthesized via an extremely concise and convergent route, which involves in essence two key C–N bondformation (amination) steps that serve to link the piperazine core between the constituent benzo[b]thiopheneand 7-butoxyquinolin-2(1H)-one fragments. The highlight of this synthesis is the first amination step, whichwas effected quite efficaciously by a novel palladium mediated Buchwald–Hartwig coupling between N-Boc-piperazine and the triflate ester of benzo[b]thiophen-4-ol (conveniently prepared in three steps fromcommercially available 6,7-dihydrobenzo[b]thiophen-4(5H)-one). Indeed, even without an extensive screeningof catalysts, ligands and reaction conditions, this amination step could be performed quite efficiently with merely1 mol% catalyst loading, which cleanly afforded in 87% overall yield 1-(benzo[b]thiophen-4-yl)piperazine—thestarting material for the second C–N bond formation and the final step in the synthesis of Brexpiprazole.