Hydrochloric Acid → N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-5-methylbenzamide Dihydrochloride

To a stirred solution of 3-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]methyl}-5-methylbenzoic acid (113 mg, 0.43 mmol) in methylene chloride (3 mL) is added HBTU (165 mg, 0.66 mmol), HOBt (89 mg, 0.66 mmol), and N,N -diisopropylethylamine (0.220 mL, 1.30 mmol), followed by (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method of Example SP-272 (175 mg, 0.43 mmol), and the reaction mixture is stirred for 12 h at room temperature. The reaction mixture is diluted with methylene chloride, washed with water, and saturated sodium bicarbonate, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 10% methanol/chloroform) affords a clear oil, which was dissolved in methanol (2 mL). To this solution is added hydrochloric acid (5 mL, 4 N dioxane, 20 mmol), and the reaction mixture is stirred for 1 h at room temperature. The reaction mixture is then diluted with ethyl ether (10 mL). The precipitate that is formed is collected by filtration to provide the title compound. ESI MS m/z 580.4 [M+H]+.

1. washwashed with water, and saturated sodium bicarbonate
2. dry with materialdried (magnesium sulfate)
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customPurification by flash column chromatography (silica, 10% methanol/chloroform)
6. customaffords a clear oil, which
7. stirringthe reaction mixture is stirred for 1 h at room temperature
8. customThe precipitate that is formed
9. filtrationis collected by filtration

ORD-Eintrag

ord-61854b262463432c81c3ce37c5f0fa04

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07727997B2