Sodium hydride → 2-hydroxy-3-{5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-indole-5-carbonitrile

HRID 2245569

Reaktionsgleichung

Reaktionsgleichung von HRID 2245569
[H-].[Na+].[O:3]=[C:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:13]#[N:14])[CH:10]=2)[NH:5]1.Cl[C:16]1[N:21]=[CH:20][C:19]([S:22]([N:25]2[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1>CN(C)C=O>[OH:3][C:4]1[NH:5][C:6]2[C:11]([C:12]=1[C:16]1[CH:17]=[CH:18][C:19]([S:22]([N:25]3[CH2:30][CH2:29][N:28]([CH3:31])[CH2:27][CH2:26]3)(=[O:24])=[O:23])=[CH:20][N:21]=1)=[CH:10][C:9]([C:13]#[N:14])=[CH:8][CH:7]=2

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 8224571-(6-Chloro-pyridine-3-sulfonyl)-4-methyl-piperazineHCID 27733462-Oxo-2,3-dihydro-1H-indole-5-carbonitrile

Produkt 1

HCID 1354426742-hydroxy-3-{5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-indole-5-carbonitrileAusbeute 10 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel3×

Versuchsvorschrift

A mixture of sodium hydride (0.157 g, 3.9 mmol, 60% dispersion in oil, pre-washed with hexane) in N,N-dimethylformamide (2 mL) was added to 2-oxoindoline-5-carbonitrile (0.464 g, 2.9 mmol) in N,N-dimethylformamide (5 mL). The formed brown mixture was stirred at room temperature for 10 min and 1-[(6-chloropyridin-3-yl)sulfonyl]-4-methylpiperazine (0.255 g, 0.92 mmol; described in: Thunus L. Annuale Pharmacetiques Francisies, 1977, 35, 197-203) in N,N-dimethylformamide (3 mL) was added. The obtained red solution was heated at 150° C. for 10 min and was then allowed to reach room temperature overnight. The solvent was removed in vacuo and the residue was partitioned between an aqueous HCl solution (2 M) and ethyl acetate. The aqueous mixture was alkalized to pH 8 by adding sodium hydrogen carbonate (s), and extracted with ethyl acetate (3×10 mL). The combined extracts were dried (Na2SO4), and the solvent was removed in vacuo. The residue was purified on a silica gel column using chloroform/methanol/conc. NH3 (aq), (84:14:2), as an eluent to afford 0.050 g. Further purification was done by preparative HPLC (Xterra column (19×300 mm) with 0.05 M NH4OAc buffer/acetonitrile, (90:10-30:70), as a eluent). Fractions containing product were collected, evaporated in vacuo, and dried at 25° C. in vacuo over night to afford 0.036 g (10% yield) of the title compound: 1H NMR (D2O, 400 MHz) δ 8.12 (s, 1H), 7.60 (d, J=10 Hz, 1H), 7.13 (s, 1H), 7.00 (dd, J=8, 2 Hz, 1H), 6.93 (d, J=9 Hz, 1H), 6.73 (dd, J=8, 2 Hz, 1H), 3.91 (d, J=13 Hz, 2H), 3.60 (d, J=11 Hz, 2H), 3.24 (app. t, J=11 Hz, 2H), 3.02 (app. t, J=12 Hz, 2H), 2.89 (s, 3H); MS (TSP) m/z 398 (M++1).

Aufarbeitung

  1. temperatureThe obtained red solution was heated at 150° C. for 10 min
  2. waitto reach room temperature overnight
  3. customThe solvent was removed in vacuo
  4. customthe residue was partitioned between an aqueous HCl solution (2 M) and ethyl acetate
  5. additionby adding sodium hydrogen carbonate (s)
  6. extractionextracted with ethyl acetate (3×10 mL)
  7. dry with materialThe combined extracts were dried (Na2SO4)
  8. customthe solvent was removed in vacuo
  9. customThe residue was purified on a silica gel column
  10. customNH3 (aq), (84:14:2), as an eluent to afford 0.050 g
  11. customFurther purification
  12. additionFractions containing product
  13. customwere collected
  14. customevaporated in vacuo
  15. customdried at 25° C. in vacuo over night

Quellen und Nachweise

ORD-Eintrag
ord-01542e83b267431bb6e378e8e4e84bad
Quelldatensatz
uspto-grants-2010_03
Patentnummer
US07683067B2

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