Acetonitrile → 2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(5-(5-isopropyl-6-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)nicotinaldehyde

Participants

Reaction Conditions

Reaction Steps

A 25-mL round-bottomed flask equipped with a reflux condenser was charged with 2-(6-tert-butyl-8-fluoro-1-oxoisoquinolin-2(1H)-yl)-4-chloronicotinaldehyde 103b (108 mg, 0.30 mmol), 151g (256 mg, 0.60 mmol), K3PO4 (127 mg, 0.60 mmol), sodium acetate.water (82 mg, 0.60 mmol), Pd(dppf)Cl2 (12 mg, 0.015 mmol), water (0.5 mL), and acetonitrile (8 mL). The reaction mixture was subjected to three cycles of vacuum/nitrogen flush and heated at 80° C. under N2 protection for 2 h. It was then cooled to room temperature and concentrated under reduced pressure. The residue was diluted with dichloromethane (20 mL) and water (10 mL). The organic layer was separated and the water layer was extracted with dichloromethane (2×10 mL). The combined organic extract was dried over Na2SO4, filtered, and concentrated under reduced pressure. The dark residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80:1 to 30:1) to afford 151h (90 mg, 48%) as yellow solid. MS-ESI: [M+H]+ 625.2.

Provenance & Evidence