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, 100 mg, 0.218 mmol) was suspended in a degassed mixture of 1,2-Dimethoxyethane (DME) (3.629 ml)/Water (0.726 ml). Then (2-fluoro-3-pyridinyl)boronic acid (92 mg, 0.653 mmol), sodium carbonate (69.2 mg, 0.653 mmol), Tetrakis (50.3 mg, 0.044 mmol) and 2-biphenylyl(dicyclohexyl)phosphane (15.26 mg, 0.044 mmol) were added and the mixture was heated to 90° C. and stirred at that temperature for 3 hours. The mixture was cooled down to room temperature, diluted with 1.3 mL of a mixture of DME/Water (5:1) then 2-biphenylyl(dicyclohexyl)phosphane (15.26 mg, 0.044 mmol), (2-fluoro-3-pyridinyl)boronic acid (92 mg, 0.653 mmol), Tetrakis (50.3 mg, 0.044 mmol) and sodium carbonate (69.2 mg, 0.653 mmol) were added again. The reaction mixture was heated to 90° C. and left stirring at that temperature for 40 minutes. The reaction mixture was cooled down to room temperature and evaporated under reduced pressure. The residue was partitioned between AcOEt and water and extracted. Organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude product was purified by Preparative HPLC affording 6-(2-fluoro-3-pyridinyl)-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 (E9, 47 mg, 0.099 mmol, 45.4% yield).

1. temperatureThe mixture was cooled down to room temperature
2. temperatureThe reaction mixture was heated to 90° C.
3. waitleft
4. stirringstirring at that temperature for 40 minutes
5. temperatureThe reaction mixture was cooled down to room temperature
6. customevaporated under reduced pressure
7. customThe residue was partitioned between AcOEt and water
8. extractionextracted
9. dry with materialOrganic phase was dried over sodium sulphate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customCrude product was purified by Preparative HPLC