1,2-Dichloroethane → 3-{[[2-(Diethylamino)ethyl](methyl)amino]methyl}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-5-methylbenzamide Trihydrochloride

Participants

Reaction Steps

To a stirred solution of 3-{[[2-(diethylamino)ethyl](methyl)amino]methyl}-5-methylbenzoic acid (267 mg, 0.959 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method of Example SP-272 (391 mg, 0.959 mmol), HOBt (129 mg, 0.959 mmol), and N,N-diisopropylethylamine (496 mg, 3.84 mmol) in methylene chloride (5 mL) is added EDC (331 mg, 1.73 mmol). The reaction mixture is stirred overnight and then partitioned between ethyl acetate and water. The organic layer is washed with 1 N hydrochloric acid, saturated sodium bicarbonate, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 9:1:1 methylene chloride/methanol/ammonium hydroxide) gives the title compound. ESI MS m/z 595.4 [M+H]+.

Provenance & Evidence