5-Chloro-[1,2,4]triazolo[4,3-a]pyridine

5193-03-3

122-51-0

27187-13-9

General procedure for the synthesis of 5-chloro-[1,2,4]triazolo[4,3-a]pyridine from 2-chloro-6-hydrazinylpyridine and triethyl orthoformate: 2-chloro-6-hydrazinylpyridine (3.0 g, 20.9 mmol) and triethyl orthoformate (20 mL, 120.2 mmol) were added to a 125 mL round bottom flask. The reaction mixture was heated to reflux for 4 hours, then cooled to room temperature and allowed to stand overnight. The mixture was concentrated to dryness under reduced pressure and trichlorophosphate (50 mL) was added. The mixture was refluxed overnight. Upon completion of the reaction, the reaction solution was quenched in an ice bath and washed with dichloromethane (CH2Cl2). The aqueous phase was adjusted to pH 6 with 1 N sodium hydroxide solution and subsequently extracted with dichloromethane. The organic phases were combined, concentrated under reduced pressure and purified by silica gel column chromatography, eluting sequentially with 100% ethyl acetate (500 mL) and 5% methanol/dichloromethane to afford 5-chloro-[1,2,4]triazolo[4,3-a]pyridine (1.73 g, 11.25 mmol, 53% yield) as a solid.