An organocatalyzed simple and general route towards the regioselective synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines and pyrido[2,3-d]pyrimidin-2-amines is developed via L-proline catalyzed domino reaction of 2-aminobenzimidazole or 2,6-diaminopyrimidin-4-one with aldehydes and β-ketoesters in water. High yields within a shorter reaction time, simple purification, and environmentally benign mild reaction conditions are the key features that make the protocol significantly applicable.