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 1407801Notes

Reaction equation

HRID 1407801 reaction equation
[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

Participants

8

Reactant 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

Product 1

HCID 593522131'-{[5-(Benzyloxy)pyridin-2-yl]methyl}spiro[furo[3,2-e][2,1,3]benzoxadiazole-8,3'-indol]-2'(1'h)-oneYield 5.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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) δ 176.0, 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).

Workup

  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)

Sources & evidence

ORD record
ord-5fc7ec1752bb4a2888a0cd753d4ccdf5
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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