反应详情

In a microwave vial was charged with 5-bromo-3-phenyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (500 mg, 1.39 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (435.6 mg, 2.09 mmol), potassium acetate (205.5 mg, 2.09 mmol), sodium carbonate (221.9 mg, 2.09 mmol), and bis(diphenylphosphino)ferrocene]dichloropalladium (II), complexed with dichloromethane (1:1) (108.3 mg, 0.13 mmol). Degassed acetonitrile (10.5 mL) and water (2.6 mL) were added. Nitrogen was passed through the mixture for 15 minutes and the vial was capped. The reaction mixture was subjected to microwave irradiation at 125° C. for 25 min. The reaction mixture was filtered through a pad of Celite® and diluted with water and EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified using flash chromatography (Si-PPC gradient elution, solvent: 60-100% ethyl acetate in heptanes, followed by 0-30% methanol in ethyl acetate) to give 5-(1-methyl-1H-pyrazol-4-yl)-3-phenyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine as a foam (340.0 mg, 67.8%). 1H NMR (400 MHz, CDCl3) δ 9.15 (s, 1H), 8.07-7.94 (m, 5H), 7.54 (t, J=7.6 Hz, 2H), 7.45 (t, J=7.4 Hz, 1H), 5.88 (dd, J=8.8, 2.2 Hz, 1H), 4.06 (dd, J=11.8, 4.0 Hz, 1H), 3.98 (s, 3H), 3.86-3.76 (m, 1H), 2.66-2.52 (m, 1H), 2.19 (d, J=10.8 Hz, 2H), 1.89-1.67 (m, 3H). LC/MS: m/z 378.3 [M+1]

1. customthe vial was capped
2. customirradiation at 125° C. for 25 min
3. filtrationThe reaction mixture was filtered through a pad of Celite®
4. additiondiluted with water and EtOAc
5. washThe organic layer was washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe crude product was purified
10. washflash chromatography (Si-PPC gradient elution, solvent: 60-100% ethyl acetate in heptanes, followed by 0-30% methanol in ethyl acetate)