反应详情

Tert-butyl 4-[2-(3,5-bis-trifluoromethyl-benzylamino)-pyrimidin-5-yloxy]-butyrate (1.11 g) and 4-benzyloxy-2-chloromethyl-5′-isopropyl-2′-methoxy-biphenyl (805 mg) are dissolved in N,N-dimethylformamide (10 ml) and thereto is added sodium hydride (60%) (120 mg) under ice-cooling, and the mixture is stirred under ice-cooling for 2 hours, and then is stirred at room temperature for 30 minutes. Thereto are added a saturated aqueous ammonium chloride solution and ethyl acetate, 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 resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=1:0→4:1) to give tert-butyl 4-{2-[(4-benzyloxy-5′-isopropyl-2′-methoxy-biphenyl-2-ylmethyl)-(3,5-bis-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate (1.14 g). MS (m/z): 824 [M+H]+.

1. temperaturecooling
2. temperaturecooling for 2 hours
3. stirringis stirred at room temperature for 30 minutes
4. customthe mixture is separated
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 silica gel column chromatography (hexane:ethyl acetate=1:0→4:1)