p-Toluenesulfonic acid → 4-(4-Chloro-2-methyl-phenyl)-1,7-dimethyl-3-(2-pyridyl)-4,6-dihydropyrazolo[3,4-e][1,4]thiazepine

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-methyl-3-(2-pyridyl)pyrazol-5-amine (0.215 g, 1.23 mmol), 4-chloro-2-methyl-benzaldehyde (0.1906 g, 1.23 mmol, Fluorochem), 1-sulfanylpropan-2-one (0.45 g, 4.93 mmol, Enamine), and p-toluenesulfonic acid (0.070 g, 0.37 mmol) in acetonitrile (3 mL) was heated, in a sealed microwave vessel, for about 30 min, at about 150° C., in a microwave. After cooling to rt the mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (70 mL) and methanol (10 mL), and washed with 5% aqueous sodium bicarbonate (20 mL). The aqueous layer was extracted with ethyl acetate (20 mL). The combined organic layers were washed with water (40 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, ethyl acetate/hexanes 1:4) to afford 4-(4-chloro-2-methyl-phenyl)-1,7-dimethyl-3-(2-pyridyl)-4,6-dihydropyrazolo[3,4-e][1,4]thiazepine (0.36 g, 0.94 mmol, 76%), as a yellow oil: LC-MS (Table 1, Method a) Rt=5.41 min, m/z 383 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.36 (3H, s) 2.60 (3H, s) 3.16 (1H, d, J=16.3 Hz) 3.29 (1H, dd, J=16.3, 1.5 Hz) 4.03 (3H, s) 6.50 (1H, d, J=8.2 Hz) 6.60 (1H, d, J=1.5 Hz) 6.88 (1H, dd, J=8.2, 2.1 Hz) 7.01 (1H, ddd, J=7.4, 4.9, 1.1 Hz) 7.16 (1H, d, J=2.1 Hz) 7.56 (1H, td, J=7.8, 1.7 Hz) 7.86 (1H, dt, J=8.1, 1.0 Hz) 8.35 (1H, ddd, J=4.8, 1.8, 0.8 Hz).

Provenance & Evidence