反应详情

A mixture of 4-(4-chloro-2-methyl-phenyl)-1,7-dimethyl-3-(2-pyridyl)-4,6-dihydropyrazolo[3,4-e][1,4]thiazepine (0.120 g, 0.31 mmol), acetic acid (0.054 mL, 0.94 mmol) and sodium triacetoxyborohydride (0.080 g, 0.38 mmol) in DCE (10 mL) was stirred at rt for about 16 h. Then more acetic acid (0.054 mL, 0.94 mmol) and sodium triacetoxyborohydride (0.080 g, 0.38 mmol) were added and stirring was continued for another 24 h. The resulting mixture was concentrated in vacuo and partitioned between 5% aqueous sodium bicarbonate (40 mL) and ethyl acetate (40 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (40 mL). The combined organic layers were washed with water (15 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, ethyl acetate/hexanes 1:1) to give 4-(4-chloro-2-methyl-phenyl)-1,7-dimethyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.100 g, 0.26 mmol, 84%) as a pale yellow solid as a mixture of two diasereomers (ratio 61:39): LC-MS (Table 1, Method e) Rt=8.51 min and 8.76 min, m/z 385 (M+H)+; Major isomer 1H-NMR (CDCl3, Bruker 400 MHz) δ 1.33 (3H, d, J=6.4 Hz) 2.58 (3H, s) 2.62-2.72 (2H, m) 3.43-3.53 (1H, m) 3.84 (3H, s) 4.06 (1H, br s) 6.59 (1H, s) 6.99 (1H, dd, J=8.3, 2.1 Hz) 7.01-7.09 (1H, m) 7.11 (1H, d, J=8.3 Hz) 7.14 (1H, d, J=2.1 Hz) 7.58 (1H, td, J=7.9, 1.9 Hz) 7.77 (1H, d, J=8.0 Hz) 8.44 (1H, d, J=4.6 Hz); Minor diastereomer: 1H-NMR (CDCl3, Bruker 400 MHz) δ 1.21 (3H, d, J=6.6 Hz) 2.55 (1H, dd, J=15.0, 8.0 Hz) 2.61 (3H, s) 2.95 (1H, dd, J=15.0, 4.3 Hz) 3.36-3.43 (1H, m) 3.86 (3H, s) 4.06 (1H, br s) 6.44 (1H, s) 6.96 (1H, dd, J=8.3, 2.1 Hz) 7.01-7.09 (1H, m) 7.06 (1H, d, J=8.0 Hz) 7.12 (1H, d, J=2.1 Hz) 7.56 (1H, td, J=7.9, 1.9 Hz) 7.76 (1H, d, J=8.0 Hz) 8.40 (1H, d, J=4.6 Hz).

1. stirringstirring
2. waitwas continued for another 24 h
3. concentrationThe resulting mixture was concentrated in vacuo
4. custompartitioned between 5% aqueous sodium bicarbonate (40 mL) and ethyl acetate (40 mL)
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with ethyl acetate (40 mL)
7. washThe combined organic layers were washed with water (15 mL)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was purified by column chromatography (SiO2, ethyl acetate/hexanes 1:1)