Ethyl Acetate → Tivantinib

HRID 63552Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 63552
[Mg].[C:2]1([C:14]2[C:15](=[O:29])[NH:16][C:17](=[O:28])[C:18]=2[C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:21][CH:20]=2)[C:12]2=[C:13]3[C:8](=[CH:9][CH:10]=[CH:11]2)[CH2:7][CH2:6][CH2:5][N:4]3[CH:3]=1.C(OCC)(=O)C>CO>[C:2]1([C@H:14]2[C@H:18]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[NH:21][CH:20]=3)[C:17](=[O:28])[NH:16][C:15]2=[O:29])[C:12]2=[C:13]3[C:8](=[CH:9][CH:10]=[CH:11]2)[CH2:7][CH2:6][CH2:5][N:4]3[CH:3]=1

Komponenten

5

Edukt 3

HCID 8857Ethyl AcetateHCID 5462224MagnesiumHCID 99692093-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione

Produkt 1

HCID 11494412TivantinibAusbeute 89,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

Magnesium turnings (3.05 g, 0.125 mol) were added to a solution of 3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4(1H-indol-3-yl)pyrrole-2,5-dione (2.56 g, 6.97 mmol) in anhydrous methanol (100 ml) and heated to reflux under an atmosphere of nitrogen for 40 minutes. After cooling to room temperature the mixture was poured into ethyl acetate (300 ml), washed with IM hydrochloric acid (300 ml) and water (500 ml). The organic layer was dried over anhydrous sodium sulfate and evaporated to dryness. The residue was then purified by silica gel chromatography using 40-50% ethyl acetate in hexanes to yield (±)-trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4(1H-indol-3-yl)pyrrolidine-2,5-dione as a pale pink solid (2.3 g). 1H NMR (DMSO-d6) 400 MHz δ: 11.54 (s, 1H), 11.03 (s, 1H), 7.32-7.4 (m, 4H), 7.17 (d, 1H, J=7.2 Hz), 7.07 (t, 1H, J=7.6 Hz), 6.96 (t, 1H, J=7.6 Hz), 6.82-6.89 (m, 2H), 4.5 (dd, 2H, J=7.2 and 20 Hz), 4.07 (t, 2H, J=5.2 Hz), 2.87 (t, 2H, J=6 Hz), 2.08 (m, 2H).

Aufarbeitung

  1. temperatureheated
  2. temperatureto reflux under an atmosphere of nitrogen for 40 minutes
  3. washwashed with IM hydrochloric acid (300 ml) and water (500 ml)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. customevaporated to dryness
  6. customThe residue was then purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-a23d63f9d4524a6e9e70e4d14b8a9d3f
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447088B2

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