A series of new N,N’-(5-(6-(4-substitutedphenyl)imidazo[2,1-b][1,3,4]-thiadiazol-2- yl)pyrimidine-2,4-diyl)diacetamide derivatives were synthesized and tested for their antibacterial activity. Guanidine carbonate & ethyl (ethoxymethylene) cyanoacetate are used as the starting materials for the preparation of ethyl-2, 4-Diaminopyrimidine-5-carboxylate (I). The reactive amino groups are acetylated using acetic anhydride in presence of DMF to form ethyl 2, 4- diacetamidopyrimidine-5-carboxylate (Ia). Efforts without masking the reactive amino groups on pyrimidine at this stage did not yield the target compounds. Further ethyl group from position 5 is removed as ethanol by refluxing Ia with 10% alcoholic NaOH for 10min to form 2, 4- diacetamidopyrimidine-5-carboxylic acid (IIa). Hence formed acid is refluxed for 4 hours with thiosemicarbazide and phosphorous oxychloride to get N, N’-(5-(5-amino-1, 3, 4-thiadiazol-2-yl) pyrimidine-2, 4-diyl) diacetamide (IIIa). Further target compounds were synthesized using different substituted phenacyl bromides. The structures of the newly synthesized compounds were confirmed by IR and 1H NMR spectroscopy. All the synthesized compounds were tested for their antibacterial activities using cup-plate-agar-diffusion method. Result of antibacterial activity reveals that the compounds IVb, IVe and IVf have shown potent activity against both grampositive and gram-negative microorganisms as compared to the standard drug methotrexate.