反应详情

温度

100 °C

Crude intermediate 5.65 from the previous step, (3,4-dimethoxyphenyl)boronic acid (34 mg, 0.19 mmol), K3PO4 (79 mg, 0.37 mmol) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (3.3 mg, 0.005 mmol) were taken up in 1,4-dioxane (1.35 mL) and water (0.14 mL) under Ar. The stirred reaction mixture was heated to 100° C. After stirring 16 h, the reaction mixture was partitioned between EtOAc, water, and brine and the resulting emulsion was filtered through a pad of Celite. The Celite was washed with DCM to elute all product and the resulting filtrate was concentrated in vacuo. The concentrate was purified by silica gel chromatography (0-20% MeOH in DCM) to provide 6-(3,4-dimethoxyphenyl)-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile 5.66. LCMS-ESI+ (m/z): [M+H]+ calcd for C21H22N5O4: 408.2; found: 407.9. 1H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 8.68 (s, 1H), 7.70 (dd, J=8.4, 2.1 Hz, 1H), 7.66 (d, J=2.1 Hz, 1H), 7.55 (s, 1H), 7.06 (d, J=8.5 Hz, 1H), 5.56-5.45 (m, 1H), 3.86 (s, 3H), 3.80 (s, 3H), 3.41-3.33 (m, 1H), 3.25-3.15 (m, 1H), 2.93-2.81 (m, 1H), 2.35-2.27 (m, 2H), 1.46 (d, J=6.2 Hz, 3H).

1. customThe stirred reaction mixture
2. customthe reaction mixture was partitioned between EtOAc, water, and brine
3. filtrationthe resulting emulsion was filtered through a pad of Celite
4. washThe Celite was washed with DCM
5. washto elute all product
6. concentrationthe resulting filtrate was concentrated in vacuo
7. customThe concentrate was purified by silica gel chromatography (0-20% MeOH in DCM)