Triphenylphosphine → 4-bromo-7-(3,3-dimethyl-2-oxopyrrolidin-1-yl)-9H-carbazole-1-carboxamide

HRID 1811163

Reaktionsgleichung

Reaktionsgleichung von HRID 1811163
[Br:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][C:10]([NH:15][C:16](=[O:23])[C:17]([CH3:22])([CH3:21])[CH2:18][CH2:19]O)=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:5]([C:24]([NH2:26])=[O:25])=[CH:4][CH:3]=1.N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.C(Cl)Cl>[Br:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][C:10]([N:15]4[CH2:19][CH2:18][C:17]([CH3:22])([CH3:21])[C:16]4=[O:23])=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:5]([C:24]([NH2:26])=[O:25])=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 593750144-bromo-7-(4-hydroxy-2,2-dimethylbutanamido)-9H-carbazole-1-carboxamide2×

Produkt 1

HCID 593750104-bromo-7-(3,3-dimethyl-2-oxopyrrolidin-1-yl)-9H-carbazole-1-carboxamideAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of 4-bromo-7-(4-hydroxy-2,2-dimethylbutanamido)-9H-carbazole-1-carboxamide (Intermediate 58-1, 89 mg, 0.213 mmol), diethyl azodicarboxylate (0.051 mL, 0.319 mmol) and triphenylphosphine (84 mg, 0.319 mmol) in THF (1 mL) was stirred at rt for 1 h. More diethyl azodicarboxylate (0.051 mL, 0.319 mmol) and triphenylphosphine (84 mg, 0.319 mmol) were added, and these additions repeated again after 1 h more. The mixture was diluted with DCM, washed with NaHCO3 (aq) and water, and dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from DCM to 90:9:1 DCM-methanol-28% aqueous ammonium hydroxide), then by preparative HPLC. The appropriate effluent fractions were made basic with 1 M aqueous sodium hydroxide and extracted twice with DCM. The combined organic phases were washed with water, dried and concentrated to provide 4-bromo-7-(3,3-dimethyl-2-oxopyrrolidin-1-yl)-9H-carbazole-1-carboxamide as a yellow solid (44 mg, 52%). 1H NMR (400 MHz, methanol-d4) δ 8.66 (1 H, d, J=8.58 Hz), 7.94 (1 H, d, J=1.54 Hz), 7.73 (1 H, d, J=8.36 Hz), 7.55 (1 H, dd, J=8.80, 1.98 Hz), 7.39 (1 H, d, J=8.14 Hz), 3.97 (2 H, t, J=6.93 Hz), 2.11 (2 H, t, J=6.93 Hz), 1.28 (6 H, s). Mass spectrum m/z 400, 402 (M+H)+.

Aufarbeitung

  1. washwashed with NaHCO3 (aq) and water
  2. customdried
  3. concentrationconcentrated
  4. customThe residue was purified by column chromatography (
  5. washeluting with a gradient from DCM to 90:9:1 DCM-methanol-28% aqueous ammonium hydroxide), then by preparative HPLC
  6. extractionextracted twice with DCM
  7. washThe combined organic phases were washed with water
  8. customdried
  9. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-03d6bfd416d247a2a47be49f7a8a880e
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362065B2

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