Various multi-substituted pyrido[1,2-a]pyrimidin-4-ones were synthesized via a one-pot tandem CuI-catalyzed C–N bond formation/intramolecular amidation reaction at 130 °C in DMF. This protocol features simple operation, broad substrate scope, good functional group tolerance and gram scale preparation, thus allowing practical and modular synthesis of pyrido[1,2-a]pyrimidin-4-ones from readily available 2-halopyridine and (Z)-3-amino-3-arylacrylate ester in good to excellent yields.