Trifluoroacetic acid → 1-Benzenesulfonyl-2,3-dihydro-1H-indole-5-carboxylic acid hydroxyamide

HRID 84192Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 84192
[NH2:1][O:2]C1CCCCO1.[C:9]1([S:15]([N:18]2[C:26]3[C:21](=[CH:22][C:23]([C:27]([OH:29])=O)=[CH:24][CH:25]=3)[CH2:20][CH2:19]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>[OH:2][NH:1][C:27]([C:23]1[CH:22]=[C:21]2[C:26](=[CH:25][CH:24]=1)[N:18]([S:15]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:17])=[O:16])[CH2:19][CH2:20]2)=[O:29]

Komponenten

8

Edukt 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 2724699PyBOPHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 25744650HCID 25744650, Verbindung

Produkt 1

HCID 534647031-Benzenesulfonyl-2,3-dihydro-1H-indole-5-carboxylic acid hydroxyamideAusbeute 95,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

NH2OTHP (0.12 g, 0.99 mmol) was added to a solution of 16 (0.25 g, 0.82 mmol), PyBOP (0.46 g, 0.87 mmol), triethylamine (0.28 ml, 1.98 mmol) in DMF (2 mL). The reaction mixture was stirred at room temperature for 1.5 h before it was quenched with water, followed by extraction with EtOAc (15 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 (2.7 ml, 36.35 mmol) in the presence of CH3OH (52 mL) and stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure to give a white residue, which was recrystallized by CH3OH to afford Compound 18 (0.25 g). 1H NMR (500 MHz, CD3OD): δ 2.95 (d, J=8.49 Hz, 2H), 3.97 (d, J=8.52 Hz, 2H), 7.48-7.52 (m, 3H), 7.57-7.63 (m, 3H), 7.82 (d, J=7.71 Hz, 2H). HRMS (EI) for C15H14N2O4S (M+): calcd, 318.0674. found, 318.0672.

Aufarbeitung

  1. customwas quenched with water
  2. extractionfollowed by extraction with EtOAc (15 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. stirringstirred overnight at room temperature
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. customto give a white residue, which
  10. customwas recrystallized by CH3OH

Quellen und Nachweise

ORD-Eintrag
ord-e5a328b1e70c423d9b86d5672d41b338
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846748B2

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