6‐Amino‐2‐thioxotetrahydropyrimidine‐5‐carbonitrile derivative 2 was synthesized in a good yield via refluxing a mixture of arylidene 1 and thiourea in a highly basic sodium ethoxide solution. Subsequently, the synthesized pyrimidine‐2‐thione derivative 2 was allowed to interact with diversified nucleophiles and electrophiles under various reaction conditions in order to have a feasible access to further new and assorted fused heterocycles. Finally, the biological activity of the newly synthesized fused pyrimidines was screened in vitro against four different Gram‐positive and Gram‐negative bacterial strains. All the developed heterocycles were adequately characterized utilizing 1H‐NMR, 13C‐NMR, Fourier transform infrared, elemental analysis, and electrospray ionization–mass spectrum and tested for their antibacterial activity.