Acetic Acid → 2,6-Dimethyl-5-(4,5,7-trifluorobenzothiazole-2-yl-methyl)-pyridin-3-yl-acetonitrile

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Reaction Steps

In a teflon screwcap glass pressure vessel a solution of 5-cyanomethyl-2,6-dimethyl-pyridin-3-yl-acetonitrile (1.5 g, 8.1 mmol), 2-amino-3,4,6-trifluoro-benzenethiol hydrochloride (2.6 g, 12.2 mmol), 2,6-di-tert-butyl-4-methylphenol (BHT) (20 mg) and acetic acid (0.56 mL, 9.8 mmol) in 2,2,2-trifluoroethanol (10 mL, 0.8 M, degassed with nitrogen) is warmed to 90° C. and stirred overnight. The mixture is cooled to room temperature, added to saturated aq sodium bicarbonate (30 mL), extracted with ethyl acetate (2×30 mL) and dried over sodium sulfate. Purification by medium-pressure liquid chromatography (MPLC) on silica (10-90% ethyl acetate in heptane) afford 2,6-dimethyl-5-(4,5,7-trifluorobenzothiazole-2-yl-methyl)-pyridin-3-yl-acetonitrile as a white solid (1.1 g, 38%); Rf 0.37 (20% ethyl acetate in heptane); 1H NMR (DMSO-d6, 300 MHz) δ 7.71 (ddd, J=10.3, 8.5, 5.4 Hz, 1H), 7.67 (s, 1 H), 4.61 (s, 2 H), 4.03 (s, 2 H), 2.44 (s, 3 H), 2.43 (s, 3 H). ESI-LCMS m/z calcd for C17H12F3N3S: 347.1; found 348.0 (M+1)+.

Provenance & Evidence