The present work describes an green and eco-friendly synthetic protocol, and vitro anti-proliferative activity of a new series of 3-arylidine imidazo[1,2-c]pyrimidines. The target molecules 4a–p were synthesized via one-pot cyclization of 6-amino-4-(4-chlorophenyl)-2- thioxo-1,2-dihydropyrimidine-5-carbonitrile(1) with chloroacetyl chloride followed by condensation with a series of aromatic and heteroaromatic aldehydes in the presence of K2CO3-NPs at room temperature. The high yield (80–96%), mild reaction conditions (short reaction time and no heat needed), simple purification, and soft, cheap, high efficiency readily available and stability of K2CO3-NPs are evident features of the present approach. Pyrimidines 4c, 4 g and 4i demonstrated significant anti-proliferative activity against MCF-7 especially compound 4i was found to be the most effective among the tested compounds with IC50 values 3.83 mg/ml in MCF-7 cell line compared to the standard drug doxorubicin. In addition, compounds 4b, 4c, 4d, 4i, and 4n demonstrated high cytotoxic activity against HCT116, particularly compound (4b) was the most potent among the tested compounds with IC50 values 9.3 mg/ml in HCT116 cell line compared to doxorubicin