Potassium Carbonate → (3R)-tert-Butyl 4-((6-(5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl)-2-(2,2-dimethyl-3-(pivaloyloxy)propyl)-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl)-3-methylpiperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Pd-118 (0.688 g) was stirred in acetonitrile (80 mL) under nitrogen and after 5 min, N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (9.26 g) was added. After 5 min, a solution of potassium carbonate (7.29 g) in water (80 mL) was added and after 10 min, a solution of (3R)-tert-butyl 4-((6-bromo-2-(2,2-dimethyl-3-(pivaloyloxy)propyl)-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl)-3-methylpiperazine-1-carboxylate (16 g) in acetonitrile (80 mL) was added and the reaction heated at 70° C. for 1.5 h. After cooling to room temperature, brine (200 mL) was added and the mixture extracted with ethyl acetate (2×125 mL). The combined organics were dried (Na2SO4), filtered and the solvents evaporated. The residue was purified (SiO2 chromatography, eluting with 20%-35% ethyl acetate/2% triethylamine in isohexane) to give the subtitle compound (14.20 g).

Provenance & Evidence