Reaction Steps
A mixture of 3-methyl-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]phenol (0.078 g, 0.22 mmol, see Ex. #D.42), potassium carbonate (0.061 g, 0.44 mmol), and 2-methyl-3-chloromethylpyridine hydrochloride (0.0356 g, 0.2 mmol, US2005/124586) in acetonitrile (10 mL) was heated at about 60° C., for about 90 h. After cooling to rt the mixture was concentrated in vacuo. The residue was treated with DCM (50 mL) and water (20 mL). The layers were separated and the organic layer was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, ethyl acetate/methanol 9:1) followed by trituration with diethyl ether to give 1-methyl-4-[2-methyl-4-[(2-methyl-3-pyridyl)methoxy]phenyl]-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.050 g. 0.11 mmol, 50%) as an off white solid: LC-MS (Table 1, Method e) Rt=5.00 min; m/z 458 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) 2.56 (3 H, s) 2.60 (3 H, s) 2.70 (1 H, ddd, J=14.9, 6.1, 2.2 Hz) 2.88 (1 H, ddd, J=14.9, 8.9, 2.6 Hz) 3.19-3.29 (1 H, m) 3.53-3.62 (1 H, m) 3.78 (1 H, br s) 3.84 (3 H, s) 4.97 (2 H, s) 6.63 (1 H, dd, J=8.4, 2.6 Hz) 6.64 (1 H, s) 6.82 (1 H, d, J=2.6 Hz) 7.07 (1 H, ddd, J=7.4, 4.9, 1.1 Hz) 7.11-7.16 (2 H, m) 7.58 (1 H, td, J=7.8, 1.9 Hz) 7.67 (1 H, dd, J=7.7, 1.1 Hz) 7.77 (1 H, dt, J=8.0, 1.0 Hz) 8.45 (1 H, dd, J=4.9, 1.6 Hz) 8.49 (1 H, d, J=4.9 Hz).
