Borane;tetrahydrofuran → (R)-4-(4-((2-(tert-butyldiphenylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide

HRID 1771174Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1771174
[Si:1]([O:18][CH2:19][CH2:20][N:21]([CH2:52][CH3:53])[C:22](=O)[CH2:23][C@@H:24]([NH:33][C:34]1[CH:39]=[CH:38][C:37]([S:40](=[O:43])(=[O:42])[NH2:41])=[CH:36][C:35]=1[S:44]([C:47]([F:50])([F:49])[F:48])(=[O:46])=[O:45])[CH2:25][S:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.C1COCC1>C1COCC1.N.CO>[Si:1]([O:18][CH2:19][CH2:20][N:21]([CH2:52][CH3:53])[CH2:22][CH2:23][C@@H:24]([NH:33][C:34]1[CH:39]=[CH:38][C:37]([S:40]([NH2:41])(=[O:42])=[O:43])=[CH:36][C:35]=1[S:44]([C:47]([F:49])([F:50])[F:48])(=[O:45])=[O:46])[CH2:25][S:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:14]([CH3:16])([CH3:15])[CH3:17])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Komponenten

6

Edukt 2

HCID 2723981Borane;tetrahydrofuran2×HCID 66723918(R)-N-(2-(tert-Butyldiphenylsilyloxy)ethyl)-N-ethyl-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluorom ethylsulfonyl)phenylamino)butanamide2×

Produkt 1

HCID 66723539(R)-4-(4-((2-(tert-butyldiphenylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamideAusbeute 48,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 222AmmoniaLösungsmittelHCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

(R)—N-(2-(tert-Butyldiphenylsilyloxy)ethyl)-N-ethyl-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanamide (INTERMEDIATE 24, 0.59 g, 0.73 mmol) was dissolved in THF (4.6 ml), under a nitrogen atmosphere, and a solution of borane-THF complex (1M in THF; 2.2 ml, 2.2 mmol) was added and the resulting solution was stirred at ambient temperature overnight. An additional solution of borane-THF complex (1M in THF; 2.2 ml, 2.2 mmol) was added. The resulting mixture was stirred at ambient for further 6 hrs. The mixture was diluted with NH3 in MeOH (7N, 20 ml) and stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, diluted with EtOAc (75 ml), washed with water (40 ml), and dried (Na2SO4). Evaporation of the volatiles under reduced pressure afforded a concentrate, which was purified by column chromatography (ISCO, 40 g silica gel column, eluting with 0→100% EtOAc/hexanes) to provide the title compound (280 mg, yield: 48%).

Aufarbeitung

  1. stirringThe resulting mixture was stirred at ambient for further 6 hrs
  2. stirringstirred at room temperature overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additiondiluted with EtOAc (75 ml)
  5. washwashed with water (40 ml)
  6. dry with materialdried (Na2SO4)
  7. customEvaporation of the volatiles under reduced pressure
  8. customafforded a concentrate, which
  9. customwas purified by column chromatography (ISCO, 40 g silica gel column, eluting with 0→100% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-6319a21e3c5b49afb50b84a31807277f
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09248140B2

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