Site selective alkoxymethylation of imidazo[4,5-b]pyridines: structural analysis by high field NMR methods

The alkylation reactions of 2-aryl- 1(3)H-imidazo[4,5-b]pyridines (equivalent to 1-deazapurines) with alkoxymethyl chlorides and bromoacetonitrile are described. The structural assignments of the products were made by the use of two-dimensional 1 H- 1 H NOE (NOESY) and selective INEPT (INAPT) 13 C nmr experiments utilizing polarization transfer from carbon-bound hydrogens in the alkyl side chains to selected 13 C resonances via long-range 3 J CH couplings. Although three isomeric N-alkyl derivatives could arise from a single heterocycle based on considerations of tautomeric equillibria, however, the reactions exhibit marked site selectivity even under quite different reaction conditions. Thus, N-3 alkyl derivatives are produced exclusively in basic (Et 3 N/NaH) nonpolar media following an S E 2cB mechanism