反应详情

温度

90 °C

6-bromo-2-(3-{1-methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (P16, 48 mg, 0.101 mmol) was suspended in a degassed mixture of 1,2-Dimethoxyethane (DME) (1.725 mL)/Water (0.345 mL). Then (2-fluoro-3-pyridinyl)boronic acid (42.9 mg, 0.304 mmol), sodium carbonate (32.2 mg, 0.304 mmol), Tetrakis (23.44 mg, 0.020 mmol) and 2-biphenylyl(dicyclohexyl)phosphane (7.11 mg, 0.020 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 (7.11 mg, 0.020 mmol), (2-fluoro-3-pyridinyl)boronic acid (42.9 mg, 0.304 mmol), Tetrakis (23.44 mg, 0.020 mmol) and sodium carbonate (32.2 mg, 0.304 mmol) were added again. The reaction mixture was then 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 then further purified by flash chromatography (SiO2, DCM to DCM/MeOH 9:1) affording 6-(2-fluoro-3-pyridinyl)-2-(3-{1-methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (Enantiomer 2) (E11, 14 mg, 0.029 mmol, 28.2% yield).

1. temperatureThe mixture was cooled down to room temperature
2. temperatureThe reaction mixture was then 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
13. customthen further purified by flash chromatography (SiO2, DCM to DCM/MeOH 9:1)