An efficient access to 3,6-disubstituted 1 H-pyrazolo[3,4- b]pyridines via a one-pot double S NAr reaction and pyrazole formation

Abstract

A general and efficient synthetic method for the synthesis of biologically important series of 3,6-disubstituted-1 H-pyrazolo[3,4- b]pyridines was discovered. 2,6-Difluoropyridine was deprotonated using 1.1 equiv of n-BuLi in THF at <−60 °C, followed by quenching with a variety of Weinreb amides to generate 2,6-Difluoro-3-ketopyridines in high yields. A mild tandem reaction sequence of selective nucleophilic substitution of the 6-fluoride with a variety of nucleophiles, followed by hydrazine substitution of the 2-fluoride and pyrazole formation in a one-pot fashion afforded a series of 3,6-disubstituted-1 H-pyrazolo[3,4- b]pyridines in moderate to good yields.