反応 #42590

反応方程式

HATU

HOBt

diisopropylethylamine

hydrochloric acid

diethyl ether

dihydrochloride

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

diisopropylethylamine

→

title compound

N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-methyl-5-(1,3-oxazol-2-yl)benzamide hydrochloride

溶媒

methanol

methylene chloride

methylene chloride

methylene chloride

反応条件

後処理

1. 1
   洗浄washed with 1 N hydrochloric acid (20 mL), saturated sodium bicarbonate (20 mL), and saturated sodium chloride
2. 2
   乾燥dried (magnesium sulfate)
3. 3
   ろ過filtered
4. 4
   濃縮concentrated under reduced pressure
5. 5
   その他Purification by flash column chromatography (silica, 1:9 methanol/chloroform)
6. 6
   その他provided a clear solid
7. 7
   ろ過The resulting precipitate was collected by filtration

実験手順

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]+.

出典