Synthesis of 3-Substituted Pyrazolo[1,5-a]pyridines by Electrophilic Reactions

Reactions of pyrazolo[l,S-alpyridines with Eschenmoser's salt, activated alkenes and alkynes, and chlorosulfonyl isocyanate provided general routes to 3-substituted pyrazolo[l,5-alpyridines such as 3-dimethylaminomethyland 3-(2-niuoethyI)pyrazolo[l J-alpyridines, l-phenyl-3-(pyrazol0[1,5-a]pyrid-3-y1)-2-propen-I-ones, 4-(pyrazolo[l,5-a]pyrid-3-yl)-3-huten-2-one, pyrazolo[l,5alpyridine-3-carboxamide, and pyrazolo[l,5-a]pyridine-3~arboniuile.The previously investigated electrophilic reactions of the pyrazolo[l,S-alpyridines (1) include hromination,' n i t r a t i ~n , ~ nitrosati~n,~ Friedel-Crafts acylation.3-5Vilsmeier-Haack reaction.5 and the acid-catalyzed reaction with aldehydes.6All of these reactions always occur at the 3-position of 1, as predicted by the frontier electron density calculation^.'^^^^As our contribution to this relatively unexplored area, we have now examined the electrophilic reactions of 1 with Eschenmoser's salt,* activated alkenes and alkynes, and chlorosulfonyl isocyanate (CSI),9 in the hope of developing general and convenient routes to the 3-substituted pyrazolo[l,S-alpyridines.