反应详情

温度

80 °C

Tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-bromo-4,5-dimethoxy-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate (150 mg) is dissolved in 1,4-dioxane (3 ml) and thereto are added (4-fluoro-5-isopropyl-2-methoxyphenyl)boronic acid (128 mg), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (32 mg) and cesium carbonate (196 mg), and the mixture is stirred under nitrogen atmosphere at 80° C. overnight. The reaction solution is cooled to room temperature, and thereto are added ethyl acetate and water, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue is purified by NH-silica gel column chromatography (hexane:ethyl acetate=19:1→17:3) to give tert-butyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(4′-fluoro-5′-isopropyl-4,5,2′-trimethoxy-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate (140 mg). MS (m/z): 796 [M+H]+

1. temperatureThe reaction solution is cooled to room temperature
2. customthe mixture is separated
3. washthe organic layer is washed with a saturated brine
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe residue is purified by NH-silica gel column chromatography (hexane:ethyl acetate=19:1→17:3)