Reaktion #42286

Reaktionsgleichung

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

Triethylamine

5-methyl-N,N-dipropylisophthalamic acid

1-Hydroxybenzotriazole

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

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

→

title compound

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

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture is warmed to 20-25 degrees C
2. 2
   Sonstigebefore recooling to 0 degrees C
3. 3
   workup.STIRRINGwith stirring
4. 4
   workup.STIRRINGThe resulting mixture is stirred at 0 degrees C
5. 5
   Temperaturwarmed to 20-25 degrees C
6. 6
   workup.WAITfor 15 hours
7. 7
   SonstigeThe reaction mixture is then quenched with aqueous citric acid (10%)
8. 8
   Extraktionthe mixture extracted three times with ethyl acetate
9. 9
   WaschenThe combined organic extracts are washed with saturated sodium bicarbonate, saline
10. 10
    Trocknendried over sodium sulfate
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated under reduced pressure

Vorschrift

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol trifluoroacetate salt (VIII, EXAMPLE 5) is dissolved in anhydrous DMF (3 mL) and cooled to 0 degrees C. Triethylamine (500 microliter, 3.6 mmol) and 5-methyl-N,N-dipropylisophthalamic acid (156 mg, 0.59 mmol) are added with stirring. The mixture is warmed to 20-25 degrees C. briefly to allow for complete dissolution of the carboxylic acid, before recooling to 0 degrees C. 1-Hydroxybenzotriazole (157 mg, 1.2 mmol) is added with stirring, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (229 mg, 1.2 mmol). The resulting mixture is stirred at 0 degrees C. for 5 minutes, then warmed to 20-25 degrees C. for 15 hours. The reaction mixture is then quenched with aqueous citric acid (10%), and the mixture extracted three times with ethyl acetate. The combined organic extracts are washed with saturated sodium bicarbonate, saline, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound in crude form. This material is purified by flash chromatography (2-10% methanol/methylene chloride gradient elution) to give purified title compound, MS (ES) MH+=582.3.

Quelle