Synthesis of ethoxyphthalimido derivatized thiazolodihydropyridines assembled with pyrazole and isoxazole systems from common intermediate chalcone and evaluation of their antibacterial activity

Condensation of aromatic aldehydes, malononitrile and thioglycolic acid gives 5-amino-3-oxo-7-substitutedphenyl-2substitutedarylidene-2,3-dihydro-7H-[1,3]thiazolo[3,2-a] pyridine-6,8-dicarbonitrile 1a-e. This acts as key intermediate for two series of final compounds 4a-e and 7a-e. In the first route compounds 1a-e are refluxed with hydroxylamine hydrochloride to yield tricyclic compound 8-amino-3,6-bis(substitutedphenyl)-1,3,3 a,9 a-tetrahydro-6H-isoxazolo[3',4':4,5][1,3]thiazolo[3,2-a]pyridin-5,7-dicarbonitrile 2a-e. These when condensed with isatin give the corresponding Schiff bases 3a-e. Condensation of 3a-e with bromoethoxyphthalimide give the final products 8-[(1 N-ethoxyphthalimido-2-oxo-1,2dihydro-3H-indol-3-ylidene)amino]-3,6-bis(substitutedphenyl)-1,3,3 a,9 a-tetrahydro-6H-isoxazolo[3',4':4,5] [1,3]thiazolo[3,2-a]pyridine-5,7-dicarbonitrile 4a-e. In the second pathway NH 2 group of compounds 1a-e is protected by bezoylation to furnish 5a-e. These α,β-unsaturated compounds (ring chalcones) when treated with hydrazine hydrate undergo cyclization to form N-(5,7-dicyano-3,6-diphenyl-2H,6 H-pyrazolo[3',4':4,5][1,3]thiazolo[3,2-a] pyridine-8-yl)benz- amide 6a-e. Active hydrogen of their pyrazole ring is replaced by ethoxyphthalimido moiety to afford the final compounds N-(5,7-dicyano-3,6bis (substitutedphenyl)-2N-ethoxyphthalimido-2H,6 H-pyrazolo[3',4':4,5][1,3]thiazolo[3,2-a] pyridine-8-yl)benzamide 7a-e. The structures of synthesized compounds have been assigned on the basis of elemental analysis and spectral data.