Acetic Acid → 2-(methylthio)-4-(1-phenyl-1H-pyrazol-5-yl)pyrimidine

Participants

Reaction Steps

A solution of (2E)-3-(dimethylamino)-1-[2-(methylthio)pyrimidin-4-yl]prop-2-en-1-one (1-4, 3.60 g, 16.1 mmol, 1 equiv), phenylhydrazine (1.58 mL, 16.1 mmol, 1.00 equiv) and acetic acid (90 uL, 1.6 mmol, 0.10 equiv) in ethanol (100 mL) was heated at reflux for 20 hours. The reaction mixture was concentrated and the residue purified by flash column chromatography (hexanes initially, grading to 40% ethyl acetate in hexanes) to give 2-(methylthio)-4-(1-phenyl-1H-pyrazol-5-yl)pyrimidine (1-5) and 2-(methylthio)-4-(1-phenyl-1H-pyrazol-3-yl)pyrimidine (1-6) as white solids. 1H NMR 1–5 (300 MHz, CDCl3) δ 8.44 (d, 1H, J=5.2 Hz), 7.77 (d, 1H, J=1.8 Hz), 7.50–7.30 (m, 5H), 6.95 (d, 1H, J=1.8 Hz), 6.92 (d, 1H, J=5.2 Hz), 2.08 (s, 3H); 1H NMR 1–6 (300 MHz, CDCl3) δ 8.60 (d, 1H, J=4.9 Hz), 8.02 (d, 1H), J=1.8 Hz), 6.92 (d, 1H, J=4.9 Hz), 7.68 (br d, 2H, j=7.8 Hz), 7.52 (br t, 2H, J=7.5 Hz), 7.37 (m, 1H), 7.23 (d, 1H, J=1.8 Hz), 2.68 (s, 3H).

Provenance & Evidence