Water → 6-(3,4-dimethoxyphenyl)-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence