反应详情

A solution of the acid from step 6 (358 mg, 1.8 mmol), HATU (1.0 g, 2.6 mmol), HOBt (357 mg, 2.6 mmol), and diisopropylethylamine (500 μL, 2.6 mmol) was stirred in methylene chloride (2.0 mL) for 15 min. A solution of dihydrochloride of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (718 mg, 1.8 mmol) and diisopropylethylamine (500 μL, 2.6 mmol) in methylene chloride (2.0 mL) was added and the reaction mixture was stirred overnight. The reaction mixture was diluted with methylene chloride, washed with 1 N hydrochloric acid (20 mL), saturated sodium bicarbonate (20 mL), and saturated sodium chloride, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provided a clear solid. The solid was dissolved in methanol (2 mL), and treated with hydrochloric acid (0.5 mL of a 1.0 M solution in diethyl ether, 0.5 mmol). The resulting precipitate was collected by filtration to provide the title compound (250 mg): mp 105-107° C.; APCI MS m/z 520 [M+H]+.

1. washwashed with 1 N hydrochloric acid (20 mL), saturated sodium bicarbonate (20 mL), and saturated sodium chloride
2. dry with materialdried (magnesium sulfate)
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customPurification by flash column chromatography (silica, 1:9 methanol/chloroform)
6. customprovided a clear solid
7. filtrationThe resulting precipitate was collected by filtration