Reaction Steps
To tert-butyl (2S)-2-[4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-3-yl]pyrrolidine-1-carboxylate (0.31 g, 0.64 mmol), was added trifluoroacetic acid in DCM (1:4, 20 mL). The resulting mixture was stirred, for about 18 h, at rt. Subsequently, 5% aqueous sodium bicarbonate (100 mL) and DCM (200 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/methanol (9:1) followed by 10% methanol in DCM) to afford 4-(2,4-dichlorophenyl)-1-methyl-3-[(2S)-pyrrolidin-2-yl]-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (38 mg, 0.1 mmol, 32%), as white solid: LC-MS (Table 1, Method a) Rt=1.38 min, m/z 383 (M+H)+; Major diastereomer; 1H NMR (400 MHz, CDCl3 and two drops of TFA) δ ppm 1.22-1.28 (1H, m) 1.85-2.35 (3H, m) 2.50-2.60 (1H, m) 2.68-2.83 (2H, m) 3.35-3.65 (3H, m) 3.75-3.85 (1H, m) 3.87 (3H, s) 4.60-4.70 (1H, br s) 5.32 (1H, s) 6.97 (1H, d, J=8.0 Hz) 7.16 (1H, dd, J=8.3, 2.2 Hz) 7.47 (1H, d, J=2.1 Hz) 9.65 (1H, br s). Minor diastereomer; 1H NMR (400 MHz, CDCl3 and two drops of TFA) δ ppm 1.22-1.28 (1H, m) 1.85-2.35 (4H, m) 2.68-2.83 (2H, m) 3.35-3.65 (3H, m) 3.75-3.85 (1H, m) 3.87 (3H, s) 4.60-4.70 (1H, br s) 5.31 (1H, s) 6.95 (1H, d, J=8.0 Hz) 7.10 (1H, dd, J=8.3, 2.2 Hz) 7.43 (1H, d, J=2.1 Hz) 9.25 (1H, br s).
