Reaction Steps
To 4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepine (0.1 g, 0.28 mmol), Example D.4) in DCM (5 mL) at 0° C., was added m-CPBA (48.5 mg, 0.28 mmol) dissolved in 3 mL DCM (dropwise in 10 min). The resulting mixture was stirred for about 10 min at rt. Subsequently, 5% aqueous sodium bicarbonate (10 mL) and DCM (20 mL) were added. The layers were separated and the organic layer was washed with water (25 mL), dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, ethyl acetate followed by 10% MeOH in ethyl acetate) to afford 4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepine 5-oxide (65 mg, 0.175 mmol, 62%), as white solid: LC-MS (Table 1, Method a) Rt=2.72 (major) and 2.97 (minor), diastereomeric ratio (64:36); m/z 372 (M+H)+; Isomer A: 1H NMR (400 MHz, CDCl3) δ ppm 1.08 (3 H, s) 1.35 (3 H, s) 1.74 (3 H, s) 3.05 (1 H, dd, J=14.7, 6.1 Hz) 3.55 (1 H, dd, J=14.7, 3.8 Hz) 3.66 (3H, s) 3.65-3.69 (1 H, m) 5.67 (1 H, s) 7.17-7.23 (2 H, m) 7.18-7.23 (1 H, m); Isomer B: 1H NMR (400 MHz, CDCl3) δ ppm 1.37 (3 H, s) 1.38 (3 H, s) 1.39 (3 H, s) 3.02 (1 H, dd, J=14.6, 7.1 Hz) 3.51 (1 H, dd, J=14.6, 2.8 Hz) 3.61 (1 H, dd, J=2.8 Hz) 3.64 (3 H, s) 5.50 (1 H, s) 7.34 (1 H, dd, J=8.6, 2.2 Hz) 7.47 (1 H, d, J=2.2 Hz) 7.89 (1 H, d, J=8.6 Hz).
