An efficient synthesis of substituted quinazoline derivatives was achieved from the reaction of 2-((1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)methyl)-4H-benzo[d][1,3] oxazin-4-one (3) as a reactive starting material with variety of nucleophilic reagents. The Structural formula of all derivatives were confirmed and characterized by elemental analysis and spectral data. Some of the synthesized compounds were also screened for their antibacterial and antifungal activities and compared with standard drugs. Most of the tested compounds showed potent to weak antimicrobial activities.