反应详情

温度

80 °C

Preparation 24, tert-butyl (3R)-3-{(3-methylpyridin-2-yl)[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl]amino}piperidine-1-carboxylate (2.67 g, 5.12 mmol), Preparation 21, 4-iodo-1-methyl-1H-pyrazole-5-carbonitrile (1.19 g, 5.12 mmol), Pd2(dba)3 (234 mg, 0.256 mmol), and XPhos (257 mg, 0.512 mmol) were dissolved in dioxane (27 mL) under nitrogen atmosphere. A solution of Na2CO3 (1.63 g, 15.4 mmol) in H2O (3 mL) was added. The reaction was heated at 80° C. for 6 h, then stirred at room temperature overnight. The reaction mixture was diluted with EtOAc (150 mL), washed by 50% brine solution (100 mL). The separated organic phase was dried over MgSO4, concentrated. The residue was purified by silica gel column chromatography eluting with a gradient of 15-100% EtOAc/heptane to afford tert-butyl (3R)-3-{[4-(5-cyano-1-methyl-1H-pyrazol-4-yl)benzoyl](3-methylpyridin-2-yl)amino}piperidine-1-carboxylate as a colorless solid (1.87 g, 73% yield).

1. washwashed by 50% brine solution (100 mL)
2. dry with materialThe separated organic phase was dried over MgSO4
3. concentrationconcentrated
4. customThe residue was purified by silica gel column chromatography
5. washeluting with a gradient of 15-100% EtOAc/heptane