Réaction #42342

Équation de réaction

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

3-[(dipropylamino)carbonyl]-5-(1H-imidazol-2-yl)benzoic acid

diisopropylethylamine

HBTU

diisopropylethylamine

→

title compound

N1-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(1H-imidazol-2-yl)-N3,N3-dipropylisophthalamide

Solvants

methylene chloride

methylene chloride

Conditions de réaction

Traitement

1. 1
   Concentrationconcentrated under reduced pressure
2. 2
   workup.ADDITIONThe residue is diluted with ethyl acetate (20 mL)
3. 3
   Lavagewashed with saturated sodium bicarbonate, and brine
4. 4
   Séchagedried (sodium sulfate)
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated under reduced pressure
7. 7
   AutrePurification by flash column chromatography (silica gel, 5:95 methanol/methylene chloride)

Mode opératoire

To a stirred solution of 3-[(dipropylamino)carbonyl]-5-(1H-imidazol-2-yl)benzoic acid (250 mg, 0.79 mmol), diisopropylethylamine (103 mg, 0.8 mmol), and HBTU (330 mg, 0.87 mmol) in methylene chloride (5 mL) is added a mixture of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method of Example SP-272 (322 mg, 0.79 mmol) and diisopropylethylamine (206 mg, 1.6 mmol) in methylene chloride (5 mL). The reaction mixture is stirred at room temperature for 4 h and concentrated under reduced pressure. The residue is diluted with ethyl acetate (20 mL), washed with saturated sodium bicarbonate, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 5:95 methanol/methylene chloride) provides the title compound in pure form. APCI MS m/z 632.3 [M+H]+.

Source