Pyrazolo pyridine electrophilic substitution

As predicted by theoretical calculations <89AP(322)885>, the site of electrophilic attack on pyrazolo[3,4-c]pyridines is C-3. Reactions such as chlorination, bromination, and nitration of the parent compound (158) all give the 3-substituted derivatives (159) <73JCS(Pl)290l, 89AP(322)885>. 

Reaction of pyrazolo[l,5-a]pyridine with n-butyllithium at —78°C selectively deprotonated C-7. This was suggested to be due to chelation with the peri nitrogen. Reaction with various electrophiles then completed a valuable method for regioselective substitution at C-7 <92JOC5538>. 

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