Dichloromethane → N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(2-methoxyethyl)(methyl)amino]methyl}-5-methylbenzamide Dihydrochloride

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Reaction Steps

To a stirred solution of 3-{[(2-methoxyethyl)(methyl)amino]methyl}-5-methylbenzoic acid (140 mg, 0.56 mmol) in methylene chloride (3 mL) is added HBTU (318 mg, 0.84 mmol), HOBt (114 mg, 0.84 mmol), and N, N-diisopropylethylamine (0.284 mL, 1.68 mmol), followed by (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method in Example SP-272 (228 mg, 0.56 mmol). The reaction mixture is stirred for 24 h at room temperature, 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 the title compound as the free base. The compound is dissolved in methanol (2 mL), and to this solution is added hydrochloric acid (5 mL, 4 N dioxane, 20 mmol). 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 554 [M+H]+.

Provenance & Evidence