反応 #42403

反応方程式

methylene chloride

3-{[(2-furylmethyl)(methyl)amino]methyl}-5-methylbenzoic acid

HBTU

HOBt

N,N-diisopropylethylamine

methylene chloride

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

→

title compound

N-{(1S,2R)-1-(3,5-Difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-{[(2-furylmethyl)(methyl)amino]methyl}-5-methylbenzamide dihydrochloride

反応条件

後処理

1. 1
   洗浄washed with water, and saturated sodium bicarbonate
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, 10% methanol/chloroform)

実験手順

To a stirred solution of 3-{[(2-furylmethyl)(methyl)amino]methyl}-5-methylbenzoic acid (170 mg, 0.66 mmol) in methylene chloride (3 mL) is added HBTU (375 mg, 0.99 mmol), HOBt (134 mg, 0.99 mmol), and N,N-diisopropylethylamine (0.334 mL, 1.98 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 (269 mg, 0.66 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 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 576 [M+H]+.

出典