5-methyl-1H-pyrazole-3-carboxylic acid → 3-[4-(2-fluoropropan-2-yl)phenyl]-5-(5-methyl-1H-pyrazol-3-yl)-1,2,4-oxadiazole

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Reaction Steps

To a mechanically stirred solution of 5-methyl-1H-pyrazole-3-carboxylic acid (1.59 g, 12.64 mmol) in dry DMF (64 mL) was added EDCl (2.42 g, 12.64 mmol), HOBT (1.71 g, 12.64 mmol) and 4-(2-fluoropropan-2-yl)-N′-hydroxybenzenecarboximidamide (Intermediate Q, 2.48 g, 12.64 mmol). The mixture was stirred at rt for 2 h, and then heated to 140° C. and stirred for additional 1 h. After being cooled to it, the solvent was removed under reduced pressure. Ethyl acetate (150 mL) and 2% aqueous citric acid solution (150 mL) were added, and the organic phase was separated and washed with saturated aqueous sodium bicarbonate solution (150 mL) and saturated aqueous sodium chloride solution. After drying over anhydrous magnesium sulfate and filtration, the solvent was removed in vacuo and the residue was purified by MPLC (silica, cyclohexane/ethyl acetate 3:1) to afford the title compound (2.48 g, 64%): 1H NMR (400 MHz, DMSO-d6) δ 13.54 (broad s, 1H), 8.08 (d, 2H), 7.62 (d, 2H), 6.81 (s, 1H), 2.33 (s, 3H), 1.72 (s, 3H), 1.68 (s, 3H); ES-MS m/z 287 (MH)+; HPLC RT (Method F) 2.19 min.

Provenance & Evidence