反应详情

温度

4 °C

To a solution of 4-(4-chloro-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,8-dihydropyrazolo[3,4-e][1,4]thiazepin-7-one (0.200 g, 0.52 mmol) in THF (6 mL) was added a solution of borane THF complex (4 mL, 1M in THF, 4 mmol, Acros) at rt. Subsequently, the mixture was heated under reflux for about 3 h. After cooling to about 4° C., HCl (5 M aqueous, 6 mL) was added dropwise and the mixture was stirred for about 2 h at about 4° C., then NaOH (1 M aqueous, 50 mL) and ethyl acetate (100 mL) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were washed with water (2×25 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by prep-HPLC (Method a, Table 2) to give 4-(4-chloro-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.0917 g, 0.25 mmol, 48%). LC-MS (Table 1, Method a) Rt=4.23 min, m/z 371 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.58 (3H, s) 2.68 (1H, ddd, J=15.0, 6.1, 2.5 Hz) 2.85 (1H, ddd, J=15.0., 9.6, 2.5 Hz) 3.21-3.29 (1H, m) 3.56-3.65 (1H, m) 3.79 (1H, br s) 3.83 (3H, s) 6.66 (1H, s) 6.99 (1H, dd J=8.3, 2.1 Hz) 7.07 (1H, ddd J=8.0, 5.0, 1.0 Hz) 7.12 (1H, d J=8.0 Hz) 7.15 (1H, d, J=2.0 Hz) 7.59 (1H, td, J=7.5, 2.0 Hz) 7.79 (1H, d, J=8.0 Hz) 8.46 (1H, d, J=4.5 Hz).

1. temperatureSubsequently, the mixture was heated
2. temperatureunder reflux for about 3 h
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
5. washThe combined organic layers were washed with water (2×25 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified by prep-HPLC (Method a, Table 2)