Reaction #42339

Reaction equation

3-[(dipropylamino)carbonyl]-5-(5-methyl-1,2,4-oxadiazol-3-yl)benzoic acid

HATU

HOBt

diisopropylethylamine

diisopropylethylamine

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

→

title compound

N1-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-(5-methyl-1,2,4-oxadiazol-3-yl)-N3,N3-dipropylisophthalamide hydrochloride

Solvents

methylene chloride

methylene chloride

methylene chloride

Conditions

Workup

1. 1
   workup.ADDITIONis added
2. 2
   Washwashed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), and brine
3. 3
   Dryingdried (magnesium sulfate)
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated under reduced pressure
6. 6
   OtherPurification by flash column chromatography (silica, 1:9 methanol/chloroform)

Procedure

A solution of 3-[(dipropylamino)carbonyl]-5-(5-methyl-1,2,4-oxadiazol-3-yl)benzoic acid (209 mg, 0.63 mmol), HATU (359 mg, 0.95 mmol), HOBt (128 mg, 0.95 mmol), and diisopropylethylamine (165 μL, 0.95 mmol) is stirred in methylene chloride (2.0 mL) for 15 min. A solution of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride prepared by the method in Example SP-272 (257 mg, 0.63 mmol) and diisopropylethylamine (165 μL, 0.95 mmol) in methylene chloride (2.0 mL) is added and the reaction mixture is stirred overnight. The reaction mixture is diluted with methylene chloride, washed with 1 N hydrochloric acid (25 mL), saturated sodium bicarbonate (25 mL), and brine, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:9 methanol/chloroform) provides the title compound as the free base. The solid is dissolved in methanol (1 mL), and treated with hydrochloric acid (0.3 mL of a 1.0 M solution in diethyl ether, 0.3 mmol). The resulting precipitate is collected by filtration to provide the title compound. APCI MS m/z 648.4 [M+H]+.

Source