Potassium Phosphate, Tribasic → 2-(5-(5-((2S,5R)-2,5-Dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)benzyl Acetate

Participants

Reaction Conditions

Reaction Steps

A 100-mL single-neck round-bottomed flask was charged with 2-bromo-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)benzyl acetate 101h (347 mg, 0.80 mmol), 3-(5-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 121g (792 mg, 1.6 mmol), Pd(dppf)Cl2 (32.7 mg, 0.040 mmol), K3PO4 (340.0 mg, 1.6 mmol), sodium acetate trihydrate (217.6 mg, 1.6 mmol), water (0.5 mL), and acetonitrile (50 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 100° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 25:1 dichloromethane/methanol to afford 126a (200 mg, 34.6%) as a yellow brown solid. MS: [M+H]+ 724.5.

Provenance & Evidence