A series of novel benzofuran scaffolds of amino pyrimidines (5a-5s) and azetidinones (17a-17j) were synthesized as potent bi-heterocyclic molecules. All the newly synthesized compounds were confirmed by spectral studies. These synthesized compounds were screened for in vivo anticancer activity. Compounds 5s, 5r and 17b displayed the highest anticancer activity against Ehrlich ascites carcinoma cells, and docking study of all the synthesized title compounds was carried out using Molegro Virtual Docker on GABA receptor-associated protein-like 1 cancer receptor. These studies revealed the importance of benzofuran, amino pyrimidines and azetidinone nucleus for their anticancer activity.