Reaktion #42324

Reaktionsgleichung

3-[(dipropylamino)-carbonyl]-5-methylbenzoic acid

3-{[[4-(benzyloxy)butyl](propyl)-amino]carbonyl}-5-methylbenzoic acid

(2R,3S)-3-amino-4-[4-(benzyloxy)phenyl]-1-[(3-methoxybenzyl)amino]-2-butanol hydrochloride

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol trifluoroacetate

N,N-diisopropylethylamine

HOBt

EDC

→

N1-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N3,N3-dipropylisophthalamide

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction mixture is partitioned between dichloromethane and water
2. 2
   SonstigeThe aqueous phase is separated
3. 3
   Extraktionextracted with dichloromethane (3×15 mL)
4. 4
   WaschenThe combined organic phases are washed with water
5. 5
   Trocknendried (magnesium sulfate)
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   SonstigePurification by flash column chromatography (silica; dichloromethane/methanol/ammonium hydroxide, 97/3/0.05)

Vorschrift

To a stirred mixture of 3-[(dipropylamino)-carbonyl]-5-methylbenzoic acid (IX, 150 mg, 0.570 mmol), (2R,3S)-3-amino-4-[4-(benzyloxy)phenyl]-1-[(3-methoxybenzyl)amino]-2-butanol hydrochloride (VIII, 274 mg, 0.571 mmol), N,N-diisopropylethylamine (400 microliter, 2.28 mmol), and HOBt (116 mg, 0.857 mmol) in dichloromethane (10 mL) is added EDC (165 mg, 0.857 mmol). The resulting mixture is stirred at 20-25 degrees C. for 16 hours. The reaction mixture is partitioned between dichloromethane and water. The aqueous phase is separated and extracted with dichloromethane (3×15 mL). The combined organic phases are washed with water, dried (magnesium sulfate), and concentrated under reduced pressure. Purification by flash column chromatography (silica; dichloromethane/methanol/ammonium hydroxide, 97/3/0.05) gives N1-{(1S,2R)-1-[4-(benzyloxy)benzyl]-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-5-methyl-N3,N3-dipropylisophthalamide, ESI-MS (m/z) [M+H]+=652.

Quelle