تفاعل #42286

معادلة التفاعل

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

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe mixture is warmed to 20-25 degrees C
2. 2
   أخرىbefore recooling to 0 degrees C
3. 3
   workup.STIRRINGwith stirring
4. 4
   workup.STIRRINGThe resulting mixture is stirred at 0 degrees C
5. 5
   درجة الحرارةwarmed to 20-25 degrees C
6. 6
   workup.WAITfor 15 hours
7. 7
   أخرىThe reaction mixture is then quenched with aqueous citric acid (10%)
8. 8
   استخلاصthe mixture extracted three times with ethyl acetate
9. 9
   غسيلThe combined organic extracts are washed with saturated sodium bicarbonate, saline
10. 10
    تجفيفdried over sodium sulfate
11. 11
    ترشيحfiltered
12. 12
    تركيزconcentrated under reduced pressure

الإجراء التجريبي

(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.

المصدر