2,2-Difluoropropionic acid → 2-(1,1-Difluoroethyl)-5-(4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-1,3,4-oxadiazole

A mixture of 4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]octane-1-carbohydrazide (4-A) (334 mg, 0.850 mmol) and 2,2-difluoropropionic acid (78 mg, 0.708 mmol) was suspended in methylene chloride, and DMC (1.2 g, 7.08 mmol) was added as solid. The mixture was stirred at room temperature under nitrogen for 48 hours before it was diluted with methylene chloride, washed with water, saturated sodium bicarbonate and brine. The crude product was purified by column chromatography to give 4-B as a white solid. MS (ESI+)=468.3 (M+1); 1H NMR (500 MHz, CDCl3): δ 2.15-2.33 (15H, m), 3.52 (3H, s), 7.61 (1H, m), 7.72 (2H, m), 7.85 (1H, m) ppm. Shh-Light II Assay: IC50: 9.3 μM.