反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 90 °C
PROCEDURE
实验过程
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-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (143 mg, 0.653 mmol), SODIUM CARBONATE (69.2 mg, 0.653 mmol), 2-biphenylyl(dicyclohexyl)phosphane (15.26 mg, 0.044 mmol) and Tetrakis (50.3 mg, 0.044 mmol) were added. The mixture was then heated at 90° C. and stirred at that temperature for 3 hours. The reaction mixture was then cooled down to room temperature, 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (143 mg, 0.653 mmol), 2-biphenylyl(dicyclohexyl)phosphane (15.26 mg, 0.044 mmol), SODIUM CARBONATE (69.2 mg, 0.653 mmol) and Tetrakis (50.3 mg, 0.044 mmol) were added again, the mixture was stirred at 90° C. for further 2 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. The residue was purified by Preparative HPLC affording 6-(2-methyl-4-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 (E3, 15.7 mg, 0.033 mmol, 15.29% yield).
WORKUP
后处理
- temperatureThe reaction mixture was then cooled down to room temperature
- stirringthe mixture was stirred at 90° C. for further 2 hours
- waitleft
- stirringstirring at room temperature overnight
- concentrationThe mixture was concentrated under reduced pressure
- custompartitioned between AcOEt and water
- customPhases were separated
- dry with materialorganic phase was dried over sodium sulphate
- concentrationconcentrated under reduced pressure
- customThe residue was purified by Preparative HPLC