反应详情

To a solution of (3S,6R)-1-(2-amino-6-chloro-4-pyrimidinyl)-6-methyl-N-phenyl-3-piperidinecarboxamide (8 g, 23.1 mmol) in 1,4-dioxane (250 mL) was added (4-cyano-3-fluorophenyl)boronic acid (5.72 g, 34.7 mmol), Pd(PPh3)4 (2.67 g, 2.3 mmol), and sat. aqueous NaHCO3 (125 mL). The resulting mixture was refluxed overnight, cooled, and diluted with H2O (˜400 mL) to form precipitate. The mixture was filtered, and the gummy solid was dissolved in EtOAc (˜800 mL) and concentrated in vacuo to about 50 mL solvent left. The crude solution was purified by silica gel chromatography (400 g column) eluting with 20% EtOAc/hexanes to 70% EtOAc/hexanes. The fractions that contained the desired product were combined and concentrated in vacuo to afford the title compound (10 g). LC-MS (ES) m/z=431 [M+H]+.

1. temperatureThe resulting mixture was refluxed overnight
2. temperaturecooled
3. customto form precipitate
4. filtrationThe mixture was filtered
5. dissolutionthe gummy solid was dissolved in EtOAc (˜800 mL)
6. concentrationconcentrated in vacuo to about 50 mL solvent
7. waitleft
8. customThe crude solution was purified by silica gel chromatography (400 g column)
9. washeluting with 20% EtOAc/hexanes to 70% EtOAc/hexanes
10. concentrationconcentrated in vacuo