In this paper, we report the facile and efficient one-pot three component synthesis of 1-((6-phenylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene)-2-(4-phenylthiazol-2-yl)hydrazine derivatives (5a-w) using an ionic liquid, 1-butyl-3-methyl imidazolium bromide ([Bmim]Br). The compounds were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis. Compound 5s showed the highest inhibitory activity with a MIC of 6.03 µM which is slightly lower than the MIC values of standard drugs ethambutol (15.3 µM) and ciprofloxacin (9.4 µM). Four other compounds of the series viz. 5e, 5i, 5t and 5w also showed significant inhibitory activity with MIC values in the range 11.7 - 13.9 µM. The structure-activity relationship revealed that a trifluoromethyl substitution at position-2 and a p-chlorophenyl substitution at position-6 of the imidazo[2,1 b][1,3,4]thiadiazole ring enhance the inhibition activity. Also, methyl, methoxy, fluoro or nitro substituents on the thiazole ring enhanced the activity of the compounds. None of the active compounds were toxic to a normal cell line (NIH 3T3) which signifies the lack of general cellular toxicity of the molecules. In silico molecular docking studies revealed the favourable interaction of the potent compounds with target enzymes, InhA and CP121.