Reaction Steps
A mixture of rac-(4R,7S)-ethyl 4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine-7-carboxylate (0.170 g, 0.174 mmol, Preparation #39) and 2 M NaOH (1 mL, 2.00 mmol) in 1,4-dioxane (2 mL) was stirred at rt for about 2 h. The reaction was partitioned between 1 M HCl (40 mL) and EtOAc (50 mL). The organic layer was washed with brine (50 mL), dried with Na2SO4, filtered and was concentrated in vacuo. The residue was suspended in THF (4 ml) and di(1H-imidazol-1-yl)methanone (0.085 g, 0.52 mmol) was added followed by DMAP (0.026 g, 0.21 mmol). The reaction was stirred at rt for about 1 h. The reaction was quenched with NH4OH (5.0 mL) and extracted with EtOAc (50 mL). The organic layer was washed with brine (50 mL), dried with Na2SO4, filtered and was concentrated in vacuo. The residue was recrystallized from DCM/Et2O to give rac-(4R,7S)-4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine-7-carboxamide (0.080 g, 0.087 mmol, 50%), as a white solid: LC-MS (Table 1, Method g) Rt=2.12 min, m/z 458/460 (M+H)+; 1H-NMR (DMSO-d6, Bruker 400 MHz) δ 8.43-8.40 (m, 1H), 7.81-7.77 (m, 1H), 7.73-7.65 (m, 1H), 7.34 (d, J=1.8 Hz, 1H), 7.23-7.19 (m, 1H), 7.17-7.12 (m, 1H), 7.11-7.08 (m, 2H), 6.99 (s, 1H), 6.61 (s, 1H), 5.82 (d, J=5.0 Hz, 1H), 4.11-4.07 (m, 1H), 3.77 (s, 3H), 3.20 (dd, J=15.2, 5.5 Hz, 1H), 2.83 (dd, J=15.3, 2.8 Hz, 1H), 2.48 (s, 3H).
