Reaktion #42388

Reaktionsgleichung

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

methylene chloride

methylene chloride

N,N-diisopropylethylamine

5-{[butyl(methyl)amino]methyl}thiophene-2-carboxylic acid

N,N-diisopropylethylamine

HBTU

methylene chloride

→

title compound

5-{[Butyl(methyl)amino]methyl}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}thiophene-2-carboxamide dihydrochloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction mixture is then stirred at room temperature overnight
2. 2
   Waschenwashed with saturated sodium bicarbonate, and brine
3. 3
   TrocknenThe organic layer is then dried (sodium sulfate)
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated under reduced pressure
6. 6
   SonstigePurification by flash column chromatography (silica, 95:5 chloroform/methanol)

Vorschrift

To a solution 5-{[butyl(methyl)amino]methyl}thiophene-2-carboxylic acid (171 mg, 0.75 mmol) and N,N-diisopropylethylamine (250 μL, 1.43 mmol) in methylene chloride (5.0 mL) is added HBTU (285 mg, 0.75 mmol) and the reaction stirred for 0.5 h. To this is added a solution of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol prepared by the method in Example SP-272 (306 mg, 0.75 mmol) in methylene chloride (5.0 mL) containing N,N-diisopropylethylamine (250 μL, 1.43 mmol). The reaction mixture is then stirred at room temperature overnight. The reaction mixture is diluted with methylene chloride, washed with saturated sodium bicarbonate, and brine. The organic layer is then dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 95:5 chloroform/methanol) gives the title compound as the free base. The solid is dissolved in methanol (1 mL) and treated with hydrochloric acid (1.0 M diethyl ether). The resulting precipitate was collected by filtration to provide the title compound. ESI MS m/z 544.3 [M+H]+.

Quelle