Trifluoroacetic acid → 3-(1-Benzenesulfonyl-1H-indol-5-yl)-N-hydroxy-acrylamide

HRID 84182

Reaktionsgleichung

Reaktionsgleichung von HRID 84182
[NH2:1][O:2]C1CCCCO1.[C:9]1([S:15]([N:18]2[C:26]3[C:21](=[CH:22][C:23]([CH:27]=[CH:28][C:29]([OH:31])=O)=[CH:24][CH:25]=3)[CH:20]=[CH:19]2)(=[O:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.C(O)(C(F)(F)F)=O>CN(C=O)C.CO>[C:9]1([S:15]([N:18]2[C:26]3[C:21](=[CH:22][C:23]([CH:27]=[CH:28][C:29]([NH:1][OH:2])=[O:31])=[CH:24][CH:25]=3)[CH:20]=[CH:19]2)(=[O:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Komponenten

8

Edukt 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 2724699PyBOPHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 674343693-[1-(Benzenesulfonyl)indol-5-YL]prop-2-enoic acid

Produkt 1

HCID 760349733-(1-Benzenesulfonyl-1H-indol-5-yl)-N-hydroxy-acrylamideAusbeute 81,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

NH2OTHP (0.43 g, 3.67 mmol) was added to a solution of 8 (1.00 g, 3.05 mmol), PyBOP (1.69 g, 3.24 mmol), and triethylamine (1.02 ml, 7.33 mmol) in DMF (1.5 mL). The reaction mixture was stirred at room temperature for 3 h before it was quenched with water and extracted with EtOAc (20 mL×3). The combined organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography (CH2Cl2:CH3OH=30:1:1% NH3(aq)) to give a white solid, which was treated with TFA (6.90 ml, 92.90 mmol) in the presence of CH3OH (140 mL). The reaction mixture was stirred overnight at room temperature. Then the mixture was concentrated under reduced pressure to give a white residue, which was recrystallized by CH3OH to afford Compound 3 (0.85 g) as a red solid. 1H NMR (500 MHz, CDCl3): δ6.42 (d, J=15.8 Hz, 1H), 6.75 (d, J=3.5 Hz, 1H), 7.49-7.54 (m, 3H), 7.59-7.62 (m, 1H), 7.61 (d, J=15.5 Hz, 1H), 7.68 (d, J=3.6 Hz, 1H), 7.72 (s, 1H), 7.93 (d, J=7.7 Hz, 2H), 7.98 (d, J=8.6 Hz, 1H). MS (EI) m/z: 327 (100%), 342 (M+, 3%). HRMS (EI) for C17H14N2O4S (M+): calcd, 342.0674. found, 342.0673.

Aufarbeitung

  1. customwas quenched with water
  2. extractionextracted with EtOAc (20 mL×3)
  3. dry with materialThe combined organic layer was dried over anhydrous MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography (CH2Cl2:CH3OH=30:1:1% NH3(aq))
  6. customto give a white solid, which
  7. stirringThe reaction mixture was stirred overnight at room temperature
  8. concentrationThen the mixture was concentrated under reduced pressure
  9. customto give a white residue, which
  10. customwas recrystallized by CH3OH

Quellen und Nachweise

ORD-Eintrag
ord-f1d491b3e98049cebbc22fd92698416e
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846748B2

Verknüpfte Notizen

Wird geladen…