Methyl iodide → 1'-[(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

HRID 2385565Notes

Reaction equation

HRID 2385565 reaction equation
[O:1]=[C:2]1[NH:7][CH:6]=[C:5]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]3([C:29]4[C:20](=[CH:21][C:22]5[O:27][CH2:26][CH2:25][O:24][C:23]=5[CH:28]=4)[O:19][CH2:18]3)[C:10]2=[O:30])[CH:4]=[CH:3]1.[H-].[Na+].I[CH3:34]>CN(C)C=O.O>[CH3:34][N:7]1[C:2](=[O:1])[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]3([C:29]4[C:20](=[CH:21][C:22]5[O:27][CH2:26][CH2:25][O:24][C:23]=5[CH:28]=4)[O:19][CH2:18]3)[C:10]2=[O:30])=[CH:6]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 593524591'-[(6-oxo-1,6-dihydropyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

Product 1

HCID 593524281'-[(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-oneYield 42.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a cooled (0° C.) solution of 1′-[(6-oxo-1,6-dihydropyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.07 g, 0.17 mmol) in anhydrous N,N-dimethylformamide (3 mL) was added sodium hydride (60% in mineral oil, 0.01 g, 0.25 mmol). The mixture was stirred at ambient temperature for 1 h, and iodomethane (0.02 mL, 0.27 mmol) was added. The mixture was stirred at ambient temperature for 16 h, diluted with water (15 mL) and extracted with ethyl acetate (3×30 mL). The combined organic layers was washed with brine (35 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with a 10% to 30% gradient of acetone in dichloromethane to afford 1′-[(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.03 g, 42%) as a colorless solid: mp 205-207° C.; 1H NMR (300 MHz, CDCl3) δ7.40-7.34 (m, 2H), 7.33-7.26 (m, 1H), 7.21-7.16 (m, 1H), 7.11-7.04 (m, 1H), 6.91-6.85 (m, 1H), 6.60-6.54 (m, 1H), 6.50 (s, 1H), 6.12 (s, 1H), 4.77 (ABq, J=75.6, 9.0 Hz, 2H), 4.66 (ABq, J=58.2, 15.3 Hz, 2H), 4.22-4.08 (m, 4H), 3.53 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 177.7, 162.5, 155.2, 144.7, 141.5, 139.6, 138.3, 137.4, 132.2, 128.9, 124.3, 123.8, 121.3, 120.7, 114.0, 111.2, 108.5, 99.5, 79.8, 64.5, 63.9, 57.9, 40.8, 37.9; MS (ES+) m/z 416.9 (M+1).

Workup

  1. stirringThe mixture was stirred at ambient temperature for 16 h
  2. extractionextracted with ethyl acetate (3×30 mL)
  3. washThe combined organic layers was washed with brine (35 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluted with a 10% to 30% gradient of acetone in dichloromethane

Sources & evidence

ORD record
ord-968170a0f9e049b5bf12ac2659d9e473
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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