Réaction #42419

Équation de réaction

hydrochloric acid

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

3-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-5-methylbenzoic acid

HBTU

HOBt

N,N -diisopropylethylamine

→

title compound

N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-5-methylbenzamide dihydrochloride

Solvants

methylene chloride

methanol

ethyl ether

methylene chloride

Conditions de réaction

Traitement

1. 1
   Lavagewashed with water, and saturated sodium bicarbonate
2. 2
   Séchagedried (magnesium sulfate)
3. 3
   Filtrationfiltered
4. 4
   Concentrationconcentrated under reduced pressure
5. 5
   AutrePurification by flash column chromatography (silica, 10% methanol/chloroform)
6. 6
   Autreaffords a clear oil, which
7. 7
   workup.STIRRINGthe reaction mixture is stirred for 1 h at room temperature
8. 8
   AutreThe precipitate that is formed
9. 9
   Filtrationis collected by filtration

Mode opératoire

To a stirred solution of 3-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-5-methylbenzoic acid (113 mg, 0.43 mmol) in methylene chloride (3 mL) is added HBTU (165 mg, 0.66 mmol), HOBt (89 mg, 0.66 mmol), and N,N -diisopropylethylamine (0.220 mL, 1.30 mmol), followed by (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method of Example SP-272 (175 mg, 0.43 mmol), and the reaction mixture is stirred for 12 h at room temperature. The reaction mixture is diluted with methylene chloride, washed with water, and saturated sodium bicarbonate, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 10% methanol/chloroform) affords a clear oil, which was dissolved in methanol (2 mL). To this solution is added hydrochloric acid (5 mL, 4 N dioxane, 20 mmol), and the reaction mixture is stirred for 1 h at room temperature. The reaction mixture is then diluted with ethyl ether (10 mL). The precipitate that is formed is collected by filtration to provide the title compound. ESI MS m/z 580.4 [M+H]+.

Source