反应详情

温度

80 °C

2-(2-(4-(7-Chloroimidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)spiro[3.3]heptan-2-yl)acetonitrile (0.200 g, 0.567 mmol), 1-(oxetan-3-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (Table 2, compound f; 0.213 g, 0.850 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.054 g, 0.113 mmol) and K3PO4 (0.85 mL, 1.7 mmol) were suspended in 1,4-dioxane (10 mL) and purged with Ar (g). Pd2dba3 (0.052 g, 0.057 mmol) was added, and the system sealed and heated at 80° C. overnight. The reaction mixture was cooled to ambient temperature and partitioned between saturated aqueous NaHCO3 and EtOAc. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure to afford the crude material, which was purified by flash column chromatography, eluting with 2-3% (9:1 MeOH:NH4OH)/DCM to provide 2-(2-(4-(7-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)spiro[3.3]heptan-2-yl)acetonitrile (0.184 g, 0.418 mmol, 74% yield). MS (apci) m/z=441.2 (M+H).

1. custompurged with Ar (g)
2. customthe system sealed
3. temperatureThe reaction mixture was cooled to ambient temperature
4. custompartitioned between saturated aqueous NaHCO3 and EtOAc
5. washThe organic layer was washed with brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto afford the crude material, which
10. customwas purified by flash column chromatography
11. washeluting with 2-3% (9:1 MeOH:NH4OH)/DCM