A concise and efficient route for the synthesis of pyrimido [1, 6-a] pyrimidines and imidazo [1, 2-c] pyrimidines by simply refluxing a reaction mixture of different heterocyclic ketene aminals and N, N′-bis (arylmethylidene) arylmethane was developed. This protocol provides an alternative method for application in combinatorial and parallel synthesis in drug discovery.