The reaction of 4-(4-chlorophenyl)-2-mercapto-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 1 with benzylidenemalononitrile and/or methyl iodide has yielded dihydropyrimido[1,2- a ]pyrimidine derivative 5 and methylthio derivative 6 respectively. Thiated product 7 was cyclized with chloroacetonitrile to give thienopyrimidine derivative 9 . Compound 6 was reacted with hydrazine hydrate to give diaminopyrimidine derivative 10 . Reaction of 10 with different reagents afforded tetrazolopyrimidine, triazolopyrimidine and pyrimidotriazepine derivatives 11 – 22 . The antimicrobial activity was studied against examples of Gram-positive and Gram-negative bacteria using Tetracycline (Antibacterial agent) and Amphotericin B (Antifungal agent) as standard.