FACILE, REGIOSELECTIVE SYNTHESES OF N-ALKYLATED 2,3-DIAMINOPYRIDINES AND IMIDAZO[4,5-B]PYRIDINES

Useful strategies are reported for the differentiation and selective s ynthetic manipulations of amino groups at the 2- and 3-positions of py ridines. It has been found that 2,3-diaminopyridine reacts with aldehy des under reductive amination conditions to give predominantly the N-3 alkylated products, which have been used for the regioselective synth esis of N-1 substituted imidazo[4,5-b]pyridines. Investigations using 2-formamido-3-aminopyridine (13), synthesized in two steps from 2-amin o-3-nitropyridine, show it to be a versatile intermediate for the regi oselective synthesis of either N-1 or N-3 substituted imidazo[4,5-b]py ridines, depending upon the conditions employed. The reductive aminati on of aldehydes with 13 using borane-pyridine in acetic acid affords t he N-1 substituted imidazo[4,5-b]pyridines in one step, whereas reacti on of 13 with alkyl halides in the presence of a suitable base (e.g., cesium carbonate) yields the N-3 substituted imidazo[4,5-b]pyridines. The generality of this synthetic methodology is noted.