Potassium Carbonate → HCID 69093144, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(2-fluorobenzyl)-3-(pyridin-2-yl)-1H-1,2,4-triazole-5-carbonitrile (I-33, 100 mg, 0.358 mmol) and potassium carbonate (198 mg, 1.43 mmol) in methanol (3.6 mL) was added hydroxylamine hydrochloride (75 mg, 1.1 mmol). The solution was heated at 70° C. for 1.25 h, at which point the solution was diluted with ethyl acetate (20 mL) and the solids were filtered off through a cotton plug. The solvent was removed in vacuo and the crude residue was diluted with water (50 mL) and a 5:1 mixture of dichloromethane and 2-propanol (50 mL). The layers were separated and the organic layer was washed with water (50 mL), dried over magnesium sulfate, and the solvent was removed in vacuo. To the resulting crude 1-(2-fluorobenzyl)-N′-hydroxy-3-(pyridin-2-yl)-1H-1,2,4-triazole-5-carboximidamide was added trimethyl orthorfomate (4.5 mL, 41 mmol) and a catalytic amount of p-toluensulfonic acid monohydrate (3.4 mg, 0.018 mmol). The solution was heated at 100° C. for 1.5 h, and the excess orthoformate was removed in vacuo to give the crude product as a dull yellow solid. Purification by silica gel chromatography (20-80% ethyl acetate in hexanes) gave 3-(1-(2-fluorobenzyl)-3-(pyridin-2-yl)-1H-1,2,4-triazol-5-yl)-1,2,4-oxadiazole, I-34 (52 mg, 0.16 mmol, 46% yield over 2 steps) as a white solid.

Provenance & Evidence