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

HRID 14110

Reaktionsgleichung

Reaktionsgleichung von HRID 14110
[CH2:1]([N:5]([CH2:7][C:8]1[S:12][C:11]([C:13]([OH:15])=O)=[CH:10][CH:9]=1)[CH3:6])[CH2:2][CH2:3][CH3:4].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:49][C@@H:50]([CH2:64][C:65]1[CH:70]=[C:69]([F:71])[CH:68]=[C:67]([F:72])[CH:66]=1)[C@H:51]([OH:63])[CH2:52][NH:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[C:57]([CH2:61][CH3:62])[CH:56]=1.C(Cl)[Cl:74]>>[ClH:74].[ClH:74].[CH2:1]([N:5]([CH2:7][C:8]1[S:12][C:11]([C:13]([NH:49][C@@H:50]([CH2:64][C:65]2[CH:66]=[C:67]([F:72])[CH:68]=[C:69]([F:71])[CH:70]=2)[C@H:51]([OH:63])[CH2:52][NH:53][CH2:54][C:55]2[CH:60]=[CH:59][CH:58]=[C:57]([CH2:61][CH3:62])[CH:56]=2)=[O:15])=[CH:10][CH:9]=1)[CH3:6])[CH2:2][CH2:3][CH3:4]

Komponenten

6

Edukt 5

HCID 6344Dichloromethane3×HCID 81531Diisopropylethylamine2×HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210859605-([Butyl(methyl)amino]methyl)thiophene-2-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Produkt 1

HCID 686084505-{[Butyl(methyl)amino]methyl}-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}thiophene-2-carboxamide Dihydrochloride

Versuchsvorschrift

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]+.

Aufarbeitung

  1. stirringThe reaction mixture is then stirred at room temperature overnight
  2. washwashed with saturated sodium bicarbonate, and brine
  3. dry with materialThe organic layer is then dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica, 95:5 chloroform/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-c17465c957cf4baf96ea07d3cf75c005
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727997B2

Verknüpfte Notizen

Wird geladen…