A series of 2,6-bis(substituted thiazolopyrimi-dinyl) pyridine (2a,b) and corresponding Schiff's bases (3a–j) were synthesized from 2,6-bis-(3-amino-2-methyl-4-oxo-9-substituted-3,4-dihydropyrido-[30,20 : 4,5]-thieno[3,2-d]pyrimidin-7-yl)pyridines (1a,b) as starting materials. The compounds 1a,b were reacted with 2,3,4,5-tetrachlorophthalic anhydride in glacial acetic acid to give the corresponding bis-imides (2a,b). But they are treated with aromatic aldehydes in refluxing ethanol to afford the Schiff’s base derivatives (3a–j). The antimicrobial screening showed that many of these newly synthesized compounds had good antimicrobial activities comparable to streptomycin and fusidic acid as positive controls. The detailed synthesis, spectroscopic data, and antimicrobial activities of the synthesized compounds were reported.