Uses
A cyano substituted triazole with inhibitory effects on cathepsin K, 3-cyano-1,2,4-triazole can be used in a study of the electrophilicity and reactivity of diverse nitrile-containing compounds and its correlation to the mechanism-of-action.
Synthesis
3-Cyano-1,2,4-triazole (3-CNT) was prepared based on the method described in U.S. Patent No. 4,522,587. The procedure was as follows: in a 250 ml three-necked flask equipped with a mechanical stirrer, a temperature probe, a cooling bath and a nitrogen protection device, 15.0 g (0.178 mol) of cyanoimidic acid hydrazide and 80.2 g (0.541 mol) of triethyl orthoformate were added. After cooling the reaction mixture to 0-5 °C, 4 g of dioxane solution pre-saturated with HCl gas was added at once. The reaction temperature was maintained at 0-5°C with stirring for 5 h. The reaction was then slowly warmed to room temperature and stirring continued until the residue of cyanoimidic acid hydrazide was less than 0.5 area % (reaction complete) as detected by HPLC. Upon completion of the reaction, the excess triethyl orthoformate was removed by distillation under reduced pressure to give the crude 3-CNT (12.3 g, HPLC purity 76 area%). The crude was suspended in a solvent mixture of 248 g of toluene and 202 g of ethyl acetate, heated to 75-80 °C and filtered to remove insoluble matter. The filtrate was concentrated under reduced pressure to obtain a slurry, after filtration, the filter cake was washed with 10 ml of toluene and dried to finally obtain 10.1 g of 3-CNT as a pale yellow solid (yield 60.2%, HPLC purity 98.7 area%).
