Hydrochloric Acid → 4-(4-Bromo-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine

Participants

Reaction Steps

To a solution of 4-(4-bromo-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,8-dihydropyrazolo[3,4-e][1,4]thiazepin-7-one (2.92 g, 6.8 mmol) in anhydrous THF (50 mL) was added a solution of borane THF complex (27.2 mL, 1M in THF, 27.2 mmol, Acros) at about 0° C. Subsequently, the mixture was stirred at rt, overnight. After cooling to about 0° C., HCl (5 M aq, 20 mL) was added dropwise and the mixture was stirred for about 30 min at rt, then the solution was brought to about pH=7 with 2 M aq NaOH, at about 0° C. The resulting mixture was extracted with ethyl acetate (200 mL). The organic layer was washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, ethyl acetate) to give 4-(4-bromo-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e]-[1,4]thiazepine (2.1 g, 5.0 mmol, 74%) as an off white solid: LC-MS (Table 1, Method e) Rt=8.32 min, m/z 415 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.58 (3H, s) 2.69 (1H, ddd, J=15.0, 6.0, 2.0 Hz) 2.86 (1H, ddd, J=15.0, 9.0, 2.5 Hz) 3.21-3.31 (1H, m) 3.57-3.65 (1H, m) 3.79 (1H, br s) 3.83 (3H, s) 6.65 (1H, s) 7.04-7.09 (2H, m) 7.14 (1H, dd, J=8.5, 2.0 Hz) 7.31 (1H, d, J=2.0 Hz) 7.59 (1H, td, J=7.5, 2.0 Hz) 7.80 (1H, br.d, J=8.0 Hz) 8.45 (1H, br.d, J=5.0 Hz).

Provenance & Evidence