反应详情

温度

100 °C

To a degassed solution of 4-(4-bromo-2-chloro-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.4 g, 0.92 mmol, see Ex. #3 step D) in 1,4-dioxane (10 mL) was added potassium carbonate (0.4 g, 2.9 mmol), trimethylboroxine (0.200 g, 1.6 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.18 mmol). The resulting mixture was heated, in a sealed microwave vessel, for about 1 h at about 100° C. in a microwave. After cooling to rt, the mixture was concentrated in vacuo. The residue was treated with water (25 mL) and ethyl acetate (150 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were washed with water (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, ethyl acetate/hexanes 1:1) to give 4-(2-chloro-4-methyl-phenyl)-1-methyl-3-(2 pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.055 g, 0.15 mmol, 60%) as an off white solid: LC-MS (Table 1, Method e) Rt=8.02 min; m/z 371 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.27 (3 H, s) 2.72 (1 H, ddd, J=15.0, 6.0, 2.5 Hz) 2.86 (1 H, ddd, J=15.0, 9.0, 2.5 Hz) 3.22-3.29 (1 H, m) 3.54-3.63 (1 H, m) 3.80 (1 H, br s) 3.84 (3 H, s) 6.75 (1 H, s) 6.89 (1 H, br.d, J=7.5 Hz) 7.07 (1 H, ddd, J=7.5, 5.0, 1.0 Hz) 7.16 (1 H, d, J=8.0 Hz) 7.22 (1 H, br.d, J=1.0 Hz) 7.58 (1H, td, J=7.5, 2.0 Hz) 7.70 (1 H, dt, J=8.0, 1.0 Hz) 8.53 (1 H, ddd, J=5.0, 2.0, 1.0 Hz).

1. temperatureAfter cooling to rt
2. concentrationthe mixture was concentrated in vacuo
3. additionThe residue was treated with water (25 mL) and ethyl acetate (150 mL)
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
6. washThe combined organic layers were washed with water (50 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe resulting residue was purified by column chromatography (SiO2, ethyl acetate/hexanes 1:1)