Design, Synthesis and Antibacterial Activity of N-(3-((4-(6-(2,2,2- Trifluoroethoxy)pyridin-3-yl)-1H-imidazol-2-yl)methyl)oxetan-3-yl)amide Derivatives

Abstract

A new series of N-(3-((4-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)-1H-imidazol-2-yl)methyl)oxetan-3- yl)amide derivatives (10a-h)were synthesized by the reaction of 3-((4-(6-(2,2,2-trifluoroethoxy)pyridin- 3-yl)-1H-imidazol-2-yl)methyl)oxetan-3-amine (8) with various carboxylic acids in the presence of T3P catalyst. The reaction is usually furnished within 60 min with good isolated yields. Coupling of 6-(2,2,2-trifluoroethoxy) nicotinic acid (1) with Weinreb amine hydrochloride gave N-methoxy-Nmethyl- 6-(2,2,2-trifluoroethoxy) nicotinamide (2). Compound 3 was synthesized by the Grignard reaction of compound 2 with methylmagnesium bromide. Bromination of compound 3 with N-bromo succinamide to obtain 2-bromo-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethan-1-one (4), which was reacted with 2-(3-(((benzyloxy)carbonyl)amino)oxetan-3-yl)acetic acid (5) gave 2-oxo-2-(6-(2,2,2- trifluoroethoxy)pyridin-3-yl)ethyl 2-(3-(((benzyloxy)carbonyl)amino)oxetan-3-yl)acetate (6). Compound 7 was synthesized by the cyclization of compound 6 with ammonium acetate. Finally, debenzylation of compound 7 gave 3-((4-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)-1H-imidazol-2- yl)methyl)oxetan-3-amine (8). All the synthesized amide compounds were characterized by analytical spectral techniques, like 1H & 13C NMR and LCMS and also evaluated their antibacterial activity.