Potassium Iodide → 1'-{[5-(Benzyloxy)pyridin-2-yl]methyl}spiro[furo[3,2-e][2,1,3]benzoxadiazole-8,3'-indol]-2'(1'h)-one

HRID 1965668Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1965668
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3[C:14]4[C:18]([CH:19]=[CH:20][C:12]=3[O:11][CH2:10]2)=[N:17][O:16][N:15]=4)[C:2]1=[O:21].[H-].[Na+].[CH2:24]([O:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:38]Cl)=[N:36][CH:37]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[I-].[K+].[Cl-].[NH4+]>CN(C)C=O.O>[CH2:24]([O:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:38][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]3([C:13]4[C:14]5=[N:15][O:16][N:17]=[C:18]5[CH:19]=[CH:20][C:12]=4[O:11][CH2:10]3)[C:2]2=[O:21])=[N:36][CH:37]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Komponenten

8

Edukt 5

HCID 4875Potassium IodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 178541585-(Benzyloxy)-2-(chloromethyl)pyridineHCID 593526377H-spiro[benzofuro[4,5-c][1,2,5]oxadiazole-8,3'-indolin]-2'-one

Produkt 1

HCID 593522131'-{[5-(Benzyloxy)pyridin-2-yl]methyl}spiro[furo[3,2-e][2,1,3]benzoxadiazole-8,3'-indol]-2'(1'h)-oneAusbeute 5,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 7H-spiro[benzofuro[4,5-c][1,2,5]oxadiazole-8,3′-indolin]-2′-one (0.400 g, 1.4 mmol) in anhydrous N,N-dimethylformamide (7 mL) was added sodium hydride (60% w/w dispersion in mineral oil, 0.086 g, 3.6 mmol) at 0° C. and the mixture was stirred for 20 minutes. 5-(Benzyloxy)-2-(chloromethyl)pyridine (0.44 g, 1.9 mmol) was added and the reaction mixture was stirred at ambient temperature for 19 h. Potassium iodide (˜10 mg, catalytic amount) was added and the reaction mixture was stirred at 60° C. for 2 h, at ambient temperature for 43 h, at 60° C. for 7 h and at ambient temperature for 3 days. Saturated aqueous ammonium chloride (7 mL) and water (30 mL) were added and the mixture was extracted with ethyl acetate (3×10 mL). The combined organic extracts were washed with water (2×20 mL) and brine (20 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with hexanes/ethyl acetate (3/2), followed by trituration in hexanes to afford 1′-{[5-(benzyloxy)pyridin-2-yl]methyl}spiro[furo[3,2-e][2,1,3]benzoxadiazole-8,3′-indol]-2′(1′H)-one (0.034 g, 5%) as a pale yellow solid: mp 209-212° C.; 1H NMR (300 MHz, CDCl3) δ 8.36 (d, J=2.7 Hz, 1H), 7.83 (d, J=9.6 Hz, 1H), 7.50 (d, J=8.7 Hz, 1H), 7.45-7.23 (m, 8H), 7.18 (d, J=7.5 Hz, 1H), 7.03 (t, J=7.5 Hz, 1H), 6.92 (J=7.8 Hz, 1H), 5.39 (d, J=15.9 Hz, 1H), 5.27 (d, J=9.6 Hz, 1H), 5.11 (s, 2H), 4.99 (d, J=9.3 Hz, 1H), 4.87 (d, J=15.9 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ176.0, 163.0, 154.4, 148.3, 147.1, 144.9, 142.2, 137.8, 136.0, 129.8, 129.7, 128.7, 128.3, 127.6, 123.7, 123.6, 122.4, 122.3, 121.9, 119.3, 110.2, 107.0, 82.0, 70.4, 57.4, 46.0; MS (ES+) m/z 477.2 (M+1).

Aufarbeitung

  1. stirringthe reaction mixture was stirred at ambient temperature for 19 h
  2. stirringthe reaction mixture was stirred at 60° C. for 2 h, at ambient temperature for 43 h, at 60° C. for 7 h and at ambient temperature for 3 days
  3. extractionthe mixture was extracted with ethyl acetate (3×10 mL)
  4. washThe combined organic extracts were washed with water (2×20 mL) and brine (20 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography
  9. washeluted with hexanes/ethyl acetate (3/2)

Quellen und Nachweise

ORD-Eintrag
ord-4b598e22791847bfbba1a41df80444ca
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415370B2

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