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

HRID 2245570

Reaktionsgleichung

Reaktionsgleichung von HRID 2245570
[H-].[Na+].[CH2:3]([NH:10][C:11]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])[CH2:16]2)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl:23][C:24]1[N:29]=[CH:28][C:27]([S:30]([N:33]2[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]2)(=[O:32])=[O:31])=[CH:26][CH:25]=1.C(=O)([O-])O.[Na+]>CCCCCC.CN(C)C=O>[ClH:23].[CH2:3]([NH:10][C:11]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([OH:22])=[C:16]2[C:24]1[CH:25]=[CH:26][C:27]([S:30]([N:33]2[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]2)(=[O:32])=[O:31])=[CH:28][N:29]=1)=[O:12])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Komponenten

7

Edukt 4

HCID 24758Sodium hydride2×HCID 516892Sodium BicarbonateHCID 8224571-(6-Chloro-pyridine-3-sulfonyl)-4-methyl-piperazineHCID 68544618N-Benzyl-2-oxoindoline-5-carboxamide

Produkt 1

HCID 135502544N-Benzyl-2-hydroxy-3-{5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl}-1H-indole-5-carboxamide hydrochlorideAusbeute 16 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8058HexaneLösungsmittel

Versuchsvorschrift

Sodium hydride (0.033 g of 60% dispersion in paraffin, 0.84 mmol) was washed with hexane, dried in vacuo and suspended in N,N-dimethylformamide (1 mL). N-Benzyl-2-oxoindoline-5-carboxamide (0.110 g, 0.41 mmol) and 1-[(6-chloropyridin-3-yl)sulfonyl]-4-methylpiperazine (0.170 g, 0.62 mmol; described in: Thunus L. Annuale Pharmacetiques Francisies, 1977, 35, 197-203) were dissolved in N,N-dimethylformamide (5 mL) and added to the suspension of sodium hydride. The reaction mixture was stirred at room temperature for 10 min and subsequently heated for 1 h at 90° C. After cooling to room temperature, a saturated aqueous sodium hydrogen carbonate solution was added (4 mL). Silica gel (8 mL) was added and the solvent was removed in vacuo. The residue was purified on a silica gel column using a gradient of chloroform/methanol mixtures, (40:1 to 1:1 and 2% triethylamine), as the eluent. The base was dissolved in a mixture of chloroform (5 mL) and methanol (5 mL). Hydrogen chloride (3 mL, 1 M in diethyl ether) was added and stirring was continued for 10 min. The precipitate was washed with diethyl ether and dried in vacuo at 60° C. to give 0.035 g (16% yield) of the title compound: 1H NMR (D2O, 400 MHz) δ 7.79 (m, 1H), 7.42 (m, 4H), 7.37 (m, 1H), 7.24 (m, 1H), 7.14 (m, 2H), 6.80 (m, 1H), 6.68 (m, 1H), 4.50 (s, 2H), 3.77 (m, 2H), 3.60 (m, 2H), 3.22 (m, 2H), 2.91 (m, 5H); MS (ES) m/z 506 (M++1).

Aufarbeitung

  1. customdried in vacuo
  2. temperaturesubsequently heated for 1 h at 90° C
  3. temperatureAfter cooling to room temperature
  4. additionSilica gel (8 mL) was added
  5. customthe solvent was removed in vacuo
  6. customThe residue was purified on a silica gel column
  7. dissolutionThe base was dissolved in a mixture of chloroform (5 mL) and methanol (5 mL)
  8. additionHydrogen chloride (3 mL, 1 M in diethyl ether) was added
  9. stirringstirring
  10. waitwas continued for 10 min
  11. washThe precipitate was washed with diethyl ether
  12. customdried in vacuo at 60° C.

Quellen und Nachweise

ORD-Eintrag
ord-d35a2bdae6db4a79ba17e7fb5a749e1a
Quelldatensatz
uspto-grants-2010_03
Patentnummer
US07683067B2

Verknüpfte Notizen

Wird geladen…