Herewith, we report the design and synthesis of a novel series of ethyl 4-(substituted phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives, obtained by condensation of substituted aldehydes, ethyl 3-oxobutanoate and urea in ethanol as solvent and Potassium tert-butoxide as a catalyst under microwave irradiation for about 10-12 min (400 W) at 70⁰C to get structural prerequisite indispensable for anticancer activity. The synthesized derivatives were investigated for MTT assay, enzymatic assay and molecular modeling studies. Most of the compounds were found to be potent in anticancer evaluation.