반응 #42286

반응 방정식

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

용매

DMF

반응 조건

후처리

1. 1
   온도The mixture is warmed to 20-25 degrees C
2. 2
   기타before recooling to 0 degrees C
3. 3
   workup.STIRRINGwith stirring
4. 4
   workup.STIRRINGThe resulting mixture is stirred at 0 degrees C
5. 5
   온도warmed to 20-25 degrees C
6. 6
   workup.WAITfor 15 hours
7. 7
   기타The reaction mixture is then quenched with aqueous citric acid (10%)
8. 8
   추출the mixture extracted three times with ethyl acetate
9. 9
   세척The combined organic extracts are washed with saturated sodium bicarbonate, saline
10. 10
    건조dried over sodium sulfate
11. 11
    여과filtered
12. 12
    농축concentrated under reduced pressure

실험 절차

(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.

출처