Regioselective N-alkylation of 2-(3,4-dimethoxyphenyl)imidazo{[}4,5-b] and {[}4,5-c]pyridine oxide derivatives : Synthesis and structure elucidation by NMR

Abstract

Imidazopyridines can exist in several tautomeric forms such as benzimidazole or purine condensed systems. Regioselectivities were determined for N-alkylations of 2-(3,4-dimethoxyphenyl)- imidazopyridines and their 4 and 5-oxides (2-4, 13, 14) with n-butyl and 4-fluorobenzyl bromides under basic conditions (K2CO3 in DMF). It was observed that N-4 (5-8) and N-5 (15-17) regioisomers were mainly formed. Compounds 7 (N-4) and 7a (N-1) were separated from the mixtures of regioisomers in a 50 : 1 ratio. Their structural assignments were made with the use of two-dimensional H-1-H-1 NOE (nuclear overhauser effect spectroscopy {[}NOESY]) enhancements between the N-CH2 and protons on the C-4, 5, 6, and 7 positions of the pyridine moiety. To verify the NOESY data, synthesis of compounds 7a and 7b was achieved by the selective method. Complementary structural information was provided by 2D-HMBC spectra of the compounds. (C) 2019 Elsevier B.V. All rights reserved.