反应详情

Poured into a suspension of 150 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride (2:1), 101 mg of 1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid, 4 mg of hydroxybenzotriazole and 76 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 6 cm3 of dichloromethane is 0.217 cm3 of N,N-diisopropylethylamine at a temperature close to 20° C. The solution is kept stirring for 24 h at a temperature close to 20° C. 15 cm3 of water are added to the reaction medium. The organic phase is washed with 5 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 product obtained is purified by flash chromatography over silica (column: 15 g; particle size: 120-40 μm, spherical; flow rate: 10 cm3/min; eluent: 100% ethyl acetate). After concentrating the fractions under reduced pressure, 140 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]-cyclopropyl}amino)propyl]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained in the form of a colorless oil.

1. customclose to 20° C
2. customclose to 20° C
3. washThe organic phase is washed with 5 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)
7. customThe product obtained
8. customis purified by flash chromatography over silica (column: 15 g; particle size: 120-40 μm, spherical; flow rate: 10 cm3/min; eluent: 100% ethyl acetate)
9. concentrationAfter concentrating the fractions under reduced pressure, 140 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]-cyclopropyl}amino)propyl]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide
10. customare obtained in the form of a colorless oil