反应详情

Poured into a suspension of 125 mg of 1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid, 170 mg of (2R,3S)-3-amino-4-phenyl-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride (2:1), 9 mg of hydroxybenzotriazole and 104 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 15 cm3 of dichloromethane is 0.444 cm3 of N,N-diisopropylethylamine at a temperature close to 20° C. The solution is kept stirring for 24 h. 15 cm3 of dichloromethane and 15 cm3 of water are added to the reaction medium. The aqueous phase is extracted with 15 cm3 of dichloromethane. The organic phases are combined, washed with 10 cm3 of a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated using a rotary evaporator under reduced pressure (5 kPa). The 350 mg of oil obtained are purified by flash chromatography over silica (column: 50 g; particle size: 120-40 μm, spherical; eluent: 100% ethyl acetate). After concentrating the fractions under reduced pressure, 79 mg of N-[(1S,2R)-1-benzyl-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained.

1. customclose to 20° C
2. extractionThe aqueous phase is extracted with 15 cm3 of dichloromethane
3. washwashed with 10 cm3 of a saturated aqueous solution of sodium chloride
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated
6. customa rotary evaporator under reduced pressure (5 kPa)