Synthesis of ortho-substituted aminopyridines. Metalation of pivaloylamino derivatives

Article abstract of DOI:10.1002/jhet.5570260119

The three isomeric pivaloylaminopyridines were lithiated in more than 80% yields. Aminopyridine derivatives were treated by 2.5-3 equivalents of the complex BuLi-TMEDA at -10° in diethyl ether. Reaction of the lithiated species with various electrophiles afforded a number of ortho-substituted pivaloylaminopyridines in good yields. Secondary pyridine alcohols were oxidized to the corresponding aminopyridyl ketones. Pyridopyrimidines, benzonaphthyridines as well as an analogue of the natural antitumor alkaloid ellipticine has been synthesized showing the versatility of the method.