Reaction Steps
To a solution of rac-methyl 4-((4R,7S)-(7-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzoate (0.300 g, 0.56 mmol) and 2-methylpyridin-3-amine (0.181 g, 1.67 mmol, Appollo) in THF (6 ml) at about 0° C. was added 1 M lithium bis(trimethylsilyl)amide in hexane (2.78 ml, 2.78 mmol). About 5 min after the complete addition, the cold bath was removed and the reaction was stirred for about 2 h at rt. The reaction was quenched with saturated NH4Cl (50 mL) and extracted with EtOAc (50 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, filtered and was concentrated in vacuo. The residue was purified by column chromatography (SiO2, 50-100% EtOAc/heptane) to give rac-4-((4R,7S)(7-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide (0.29 g, 0.47 mmol, 85%) as a pale yellow film: LC-MS (Table 1, Method g) Rt=2.83 min, m/z 615 (M+H)+; 1H-NMR (DMSO-d6, Bruker 400 MHz) δ 9.84 (s, 1H), 8.48-8.44 (m, 1H), 8.30 (d, J=4.6 Hz, 1H), 7.81-7.78 (m, 1H), 7.73-7.66 (m, 2H), 7.64-7.60 (m, 1H), 7.39-7.36 (m, 1H), 7.28-7.16 (m, 2H), 6.87 (d, J=3.1 Hz, 1H), 6.80 (s, 1H), 5.86 (d, J=5.2 Hz, 1H), 4.96 (s, 1H), 3.78-3.61 (m, 4H), 3.52 (s, 1H), 2.87-2.74 (m, 2H), 2.57 (s, 3H), 2.40 (s, 3H), 0.83 (s, 9H), 0.12-−0.15 (m, 6H).
