In this research work, O, N-heterocycles were prepared using the domino Knoevenagel-hetero Diels-Alder reaction. Seven novel heterocycles were synthesized with moderate to good yield, using five different cyclic 1,3-dicarbonyl derivatives. Their structures were analyzed by NMR and by comparing them with the previously prepared analogs. No other ring-closure mechanism was observed in these reactions. Based on the previous studies in our research group, these compounds can have very good antiproliferative activities.