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1,2,3,4-Tetrahydroquinazoline is an important scaffold due to variety of pharmacological properties associated with the derivatives bearing this heterocyclic. Especially their importance in the cancer chemotherapy is unparallel. In our efforts to discover new chemical pharmacophore which may lead to formation of new anticancer agent. The essence of work is to synthesize different substituted tetrahydroquinazoline fused with substituted benzo[d]isothiazol-3(2H)-one and to test them for their anticancer activity in vitro. Novel compounds as potent inhibitors of EGF receptor tyrosine kinase inhibitors. In the light of above, 3rd position of tetrahydroquinazoline ring were explored to obtain different derivatives. The reaction was monitored by Thin Layer Chromatography (TLC) using suitable mobile phase. The Rf values were compared and determined the Melting Point (MP) of derivatives. It is found that they were different from each other's. Further, these derivatives were characterizedand confirmed by IR, 1H-NMR, 13C-NMR, and Mass spectral studies.