Efficient one-pot synthesis of functionalised imidazo[1,2-]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. An efficient one-pot procedure for isocyanide preparation and imidazo[1,2- a ]pyridine synthesis gave products able to undergo intramolecular ring-closure to afford novel tetracycles.