Water → HCID 178502381, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of [(S)-2-methyl-1-((S)-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (1.80 g, 3.63 mmol) and 4-bromo-3-trifluoromethoxy-phenylamine (1.00 g, 3.90 mmol) dissolved in toluene (5.4 mL) and water (2.7 mL) was added potassium carbonate (2.50 g, 18.1 mmol). The reaction mixture was sparged with nitrogen. Tetrakis(triphenylphosphine)-palladium(0) (0.21 g, 0.18 mmol) was added and the reaction mixture was sparged with nitrogen and heated at 100° C. in a sealed tube overnight, diluted in ethyl acetate (100 mL) and washed with water, brine. The organic layer was dried over sodium sulfate, filtered, and concentrated to produce a red paste (6.5 g), which was purified by silica gel chromatography (120 g silica, 0-3% MeOH/DCM) to provide the title intermediate (1.05 g) and a second fraction which was purified by reverse phase HPLC to provide the di-TFA salt of the title intermediate (800 mg). (Total yield 80%).

Provenance & Evidence