Cyclization of isothiosemicarbazones. Part 10. A novel route to 2-amino[1,2,4]triazolo[1,5-a]pyridine derivatives

Abstract

2-Alkylamino[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile and 8-carboxylate derivatives 3 are obtained directly in moderate yields by the reaction of ketone isothiosemicarbazones 1, carrying a bulky alkyl group on the terminal nitrogen and at least one α-methylene group, with an active ethoxymethylene compound with elimination of a thiol. Butanone isothiosemicarbazone 1e gives an isomeric pair of 5-ethyl- and 5,6-dimethyl-triazolopyridines 3e and 3f depending upon which of the α-carbons is incorporated into the ring system, with the 5,6-dimethyl compound being the major product. When the substituent on the terminal nitrogen is less bulky, the reaction gives both [1,2,4]triazolo[1,5-a]pyridines 3 and penta-substituted 2-triazolines 4 or the latter compounds only. A plausible reaction mechanism is proposed.