Efficient one-pot synthesis of functionalised imidazo[1,2-a]pyridines and unexpected synthesis of novel tetracyclic derivatives by nucleophilic aromatic substitution

Novel tetracyclic imidazo[1,2-a]pyridine derivatives have been prepared by intramolecular nucleophilic aromatic substitution of 5-fluoroimidazo[1,2-a]pyridines under basic conditions. Use of the non-nucleophilic alcoholic solvent tert-butanol, rather than methanol, increased the yield of the tetracycles by reducing the competing intermolecular reaction observed for methanol. In addition, a modified protocol for the dehydration of formamides to isocyanides has been found to be tolerant of an unprotected hydroxyl functional group and one-pot conversion to imidazo[1,2-a]pyridyl-aminocyclohexanol analogues is reported.