反应详情

温度

90 °C

6-bromo-2-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (P8, 170 mg, 0.370 mmol) was suspended in a degassed mixture of 1,2-Dimethoxyethane (DME) (6169 ply Water (1234 μl), then 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazole (266 mg, 1.110 mmol), SODIUM CARBONATE (118 mg, 1.110 mmol), 2-biphenylyl(dicyclohexyl)phosphane (25.9 mg, 0.074 mmol) and Tetrakis (86 mg, 0.074 mmol) were added. The mixture was then heated at 90° C. and stirred at that temperature for 3 hours. Then the reaction mixture was cooled down to room temperature and 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazole (266 mg, 1.110 mmol), 2-biphenylyl(dicyclohexyl)phosphane (25.9 mg, 0.074 mmol), SODIUM CARBONATE (118 mg, 1.110 mmol) and Tetrakis (86 mg, 0.074 mmol) were added again. The mixture was stirred at 90° C. for further 4 hours, then left stirring at room temperature overnight. The mixture was concentrated under reduced pressure and partitioned between AcOEt and water. Phases were separated, organic phase was dried over sodium sulphate and concentrated under reduced pressure. Crude product was purified by Preparative HPLC then further purified by flash chromatography (SiO2; eluent: DCM to DCM/MeOH 9:1) affording 6-(2,4-dimethyl-1,3-thiazol-5-yl)-2-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (E7, 44.3 mg, 0.090 mmol, 24.35% yield).

1. temperatureThen the reaction mixture was cooled down to room temperature
2. stirringThe mixture was stirred at 90° C. for further 4 hours
3. waitleft
4. stirringstirring at room temperature overnight
5. concentrationThe mixture was concentrated under reduced pressure
6. custompartitioned between AcOEt and water
7. customPhases were separated
8. dry with materialorganic phase was dried over sodium sulphate
9. concentrationconcentrated under reduced pressure
10. customCrude product was purified by Preparative HPLC
11. customthen further purified by flash chromatography (SiO2; eluent: DCM to DCM/MeOH 9:1)