反应详情

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol (VIII, EXAMPLE 6) is dissolved in anhydrous DMF (3 mL) and cooled to 0°. Triethylamine (500 μL, 3.6 mmol) and 5-methyl-N, N-dipropylisophthalamic acid (IX, 156 mg, 0.59 mmol) are added with stirring. The mixture is warmed to 20-25° briefly to allow for complete dissolution of the carboxylic acid, before recooling to 00. 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° for 5 min, then warmed to 20-25° for 15 hr. The 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.

1. temperaturecooled to 0°
2. temperatureThe mixture is warmed to 20-25° briefly
3. stirringwith stirring
4. stirringThe resulting mixture is stirred at 0° for 5 min
5. temperaturewarmed to 20-25° for 15 hr
6. customThe mixture is then quenched with aqueous citric acid (10%)
7. extractionthe mixture extracted three times with ethyl acetate
8. washThe combined organic extracts are washed with saturated sodium bicarbonate, saline
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure