Methanesulfonic Acid → 5-[4-(2-Trifluoromethylbenzoyl)piperazin-1-YL]-[1,3,4]thiadiazole-2-carboxylic acid ethyl ester

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Reaction Steps

Oxo-{N′-[4-(2-trifluoromethylbenzoyl)piperazine-1-carbothioyl]hydrazino}-acetic acid ethyl ester (2.88 g, 6.56 mmol) was dissolved in a mixture of 50 mL of toluene and 10 mL of N-methyl-2-pyrrolidone. Methanesulfonic acid (0.723 mL, 11.15 mmol) was then added dropwise over 5 minutes to the stirred solution. The mixture was refluxed for 1.5 hours, then evaporated to 10 mL, and then 20 mL of water was added. The pH of the solution was adjusted to 8 by saturated NaHCO3. The mixture was extracted with ethyl acetate (2×50 mL). The combined organic phase was washed with brine, dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash chromatography to give the title compound in 68% yield (1.84 g). 1H NMR (500 MHz, CDCl3) δ 7.74 (d, J=7.8 Hz, 1H), 7.64 (dd, J=7.5, 7.5 Hz, 1H), 7.60 (dd, J=7.5, 7.5 Hz, 1H), 7.35 (d, J=7.3 Hz, 1H), 4.44 (q, J=7.1 Hz, 2H), 4.06-4.11 (m, 1H), 3.86-3.91 (m, 1H), 3.56-3.77 (m, 4H), 3.35 (t, J=5.4 Hz, 2H), 1.41 (t, J=7.1 Hz, 3H). MS (ES+) m/z 415.5 (M+1).

Provenance & Evidence