Reaction Steps
To a mixture of methyl 3-methyl-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzoate (0.20 g, 0.51 mmol) and 3-amino-2-methylpyridine (0.066 g, 0.61 mmol) in anhydrous THF (20 mL), was added lithium bis(trimethylsilyl)amide solution (1.01 mL, 1 M in THF, 1.01 mmol), at about −60° C. The resulting mixture was stirred for about 30 min, during which time the temperature was allowed to rise from about −60° C. to about 0° C., and then quenched by the addition of water (20 mL), while keeping the temperature below 0° C. The resulting mixture was extracted with ethyl acetate (60 mL). The organic layer was washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, ethyl acetate) to afford 3-methyl-N-(2-methyl-3-pyridyl)-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzamide (0.10 g, 0.21 mmol, 42%) as a beige foam: LC-MS (Table 1, Method a) Rt=1.85 min, m/z 471 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.56 (3H, s) 2.72 (3H, s) 2.67-2.75 (1H, m) 2.87 (1H, ddd, J=15.0, 9.3, 2.6 Hz) 3.29 (1H, ddd, J=13.3, 9.3, 2.5 Hz) 3.65 (1H, ddd, J=13.3, 6.2, 2.3 Hz) 3.85 (3H, s) 3.87 (1H, br s) 6.76 (1H, s) 7.08 (1H, ddd, J=7.4, 4.9, 1.1 Hz) 7.20 (1H, dd, J=8.1, 4.7 Hz) 7.35 (1H, t, J=8.0 Hz) 7.55 (1H, dd, J=8.0, 2.0 Hz) 7.60 (1H, td, J=7.8, 1.8 Hz) 7.62 (1H, d, J=1.8 Hz) 7.69 (1H, br s) 7.84 (1H, dt, J=8.0, 1.0 Hz) 8.30 (1H, dd, J=4.8, 1.6 Hz) 8.35 (1H, dd, J=8.1, 1.4 Hz) 8.47 (1H, ddd, J=4.8, 1.7, 0.8 Hz).
