反应详情

温度

100 °C

Intermediate 5.64 (218 mg, 0.496 mmol), (4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)boronic acid (303 mg, 0.99 mmol), K3PO4 (420 mg, 2.0 mmol) and Bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium (II) (18 mg, 0.025 mmol) were taken up in 1,4-dioxane (7 mL) and water (0.72 mL). The stirred reaction mixture was heated to 100° C. Once complete, the reaction mixture was partitioned between EtOAc, water, and brine. The phases were separated and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography to provide tert-butyl 4-(4-(3-cyano-4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazin-6-yl)phenyl)piperazine-1-carboxylate. LCMS-ESI+ (m/z): [M+H]+ calcd for C37H44N7O5: 666.3; found: 666.3.

1. customThe stirred reaction mixture
2. customOnce complete, the reaction mixture was partitioned between EtOAc, water, and brine
3. customThe phases were separated
4. extractionthe aqueous phase was extracted with EtOAc
5. dry with materialThe combined organic phase was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude residue was purified by silica gel chromatography