Sodium hydride → HCID 136342115, Verbindung

HRID 748532Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 748532
[H-].[Na+].[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)#[N:4].Cl[C:16]1[CH:17]=[C:18]([CH:27]=[CH:28][N:29]=1)[C:19]([NH:21][CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])=[O:20]>CN(C)C=O>[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([OH:14])=[C:8]2[C:16]1[CH:17]=[C:18]([CH:27]=[CH:28][N:29]=1)[C:19]([NH:21][CH2:22][CH2:23][N:24]([CH3:25])[CH3:26])=[O:20])#[N:4]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 27733462-Oxo-2,3-dihydro-1H-indole-5-carbonitrileHCID 28375983HCID 28375983, Verbindung

Produkt 1

HCID 136342115HCID 136342115, VerbindungAusbeute 5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel3×

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a suspension of sodium hydride (0.15 g, 3.70 mmol, 60% dispersion in oil, pre-washed with hexane) in N,N-dimethylformamide (3 mL) was added a solution of 5-cyanooxindole (0.29 g, 1.84 mmol) in N,N-dimethylformamide (4 mL). The mixture was stirred for 30 min under a nitrogen atmosphere. 2-Chloro-N-[2-(dimethylamino)ethyl]isonicotinamide (0.21 g, 0.92 mmol) dissolved in N,N-dimethylformamide (4 mL) was added dropwise and the mixture was stirred at room temperature for 30 min and then heated at 150° C. for 45 min. The solvent was evaporated in vacuo and the residue was partitioned between ethyl acetate and water. A 2 M aqueous HCl solution was added until pH 2 and the mixture was extracted with ethyl acetate. To the aqueous layer, a 45% aqueous NaOH solution was added until pH 11 and the suspension was extracted with ethyl acetate. The aqueous layer was concentrated in vacuo and the crude product was purified by preparative HPLC (column: Xterra, 19×300 mm, eluent: 0.05 M NH4OAc buffert/acetonitrile, 9:1 to 3:7) to give 15 mg (5% yield) of the title compound as a red solid: 1H NMR (DMSO-d6, 400 MHz) δ 14.88 (br s, 1 H), 11.03 (br s, 1 H), 9.10 (br s, 1 H), 8.28 (d, J=6 Hz, 1 H), 8.04-7.96 (m, 1 H), 7.95-7.83 (m, 1 H), 7.42-7.34 (m, 1 H), 7.13-7.02 (m, 2 H), 3.62-3.50 (m, 2 H), 2.86-2.69 (m,.2 H), 2.58-2.29 (m, 6 H); MS (TSP) m/z 350 (M++1).

Aufarbeitung

  1. additionwas added dropwise
  2. stirringthe mixture was stirred at room temperature for 30 min
  3. customThe solvent was evaporated in vacuo
  4. customthe residue was partitioned between ethyl acetate and water
  5. additionA 2 M aqueous HCl solution was added until pH 2
  6. extractionthe mixture was extracted with ethyl acetate
  7. additionTo the aqueous layer, a 45% aqueous NaOH solution was added until pH 11
  8. extractionthe suspension was extracted with ethyl acetate
  9. concentrationThe aqueous layer was concentrated in vacuo
  10. customthe crude product was purified by preparative HPLC (column: Xterra, 19×300 mm, eluent: 0.05 M NH4OAc buffert/acetonitrile, 9:1 to 3:7)

Quellen und Nachweise

ORD-Eintrag
ord-faa9921d2df7450b9cf15dd83a880023
Quelldatensatz
uspto-grants-2008_07
Patentnummer
US07399780B2

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