反应详情

To tetrahydrofuran (6 ml) is added sodium hydride (60%) (390 mg) under nitrogen atmosphere, followed by an addition dropwise of benzyl alcohol (1.01 ml) under water-cooling, and the mixture is stirred at the same temperature for 30 minutes. To this reaction mixture is added a mixture of (3-fluoro-5-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine (430 mg) and tetrahydrofuran (4 ml) and the mixture is stirred under nitrogen atmosphere at 70° C. overnight. To the reaction solution are added a saturated brine, and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by NH-silica gel column chromatography (hexane:ethyl acetate=97:3→17:3) to give (3-benzyloxy-5-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amine (221 mg). MS (m/z): 751 [M+H]+

1. temperaturecooling
2. additionTo this reaction mixture is added
3. stirringthe mixture is stirred under nitrogen atmosphere at 70° C. overnight
4. extractionthe mixture is extracted with ethyl acetate
5. washThe organic layer is washed with a saturated brine
6. dry with materialdried over magnesium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe resulting residue is purified by NH-silica gel column chromatography (hexane:ethyl acetate=97:3→17:3)