Potassium Carbonate → Tert-butyl 4-[(2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of tert-butyl 4-[(6-bromo-2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate (Example 27c, 0.153 g) in DMF (4 mL) was treated with N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.077 g), Pd-118 (4.71 mg) and potassium carbonate (0.067 g) under nitrogen. The resulting mixture was stirred at 75° C. for 8 h. The reaction was partitioned between ethyl acetate and water. The aqueous was extracted with ethyl acetate (2×100 mL) before washing the organics with water (3×100 mL) and brine (3×100 mL). The organic was dried (MgSO4), filtered, and evaporated under reduced pressure to afford the crude product. The crude product was purified (SiO2 chromatography, elution with 30% ethyl acetate/isohexane) to afford the subtitle compound (0.099 g) as an oil.

Provenance & Evidence