Methyl iodide → HCID 86592635, compound

HRID 897240Notes

Reaction equation

HRID 897240 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][C:8](=[O:13])[CH:7]=[C:6]2[NH:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.[NH:21]1[C:29]2[C:24](=[CH:25][C:26]([CH:30]=O)=[CH:27][CH:28]=2)[CH:23]=[CH:22]1.[H-].[Na+].[CH3:34]I>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][C:8](=[O:13])[CH:7]=[C:6]2[N:14]([CH:15]1[CH2:20][CH2:19][N:18]([CH2:30][C:26]2[CH:25]=[C:24]3[C:29](=[CH:28][CH:27]=2)[NH:21][CH:22]=[CH:23]3)[CH2:17][CH2:16]1)[CH3:34]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 589040Indole-5-carboxaldehydeHCID 22348060HCID 22348060, compound

Product 1

HCID 86592635HCID 86592635, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

6-Methoxy-4-(piperidin-4-ylamino)-chromen-2-one and indole-5-carboxaldehyde were allowed to react under reductive alkylation conditions to give a crude beige product. After trituration of the crude product with hot ethyl acetate, filtration and concentration, the resulting partially-purified white powder was carried on to the subsequent alkylation step. A solution of this material (202 mg, 0.5 mmol) in 2 mL DMF under nitrogen at 0° C., was treated with NaH (60% dispersion in mineral oil, 50 mg, 12.5 mmol). After 45 minutes, methyl iodide (33 uL, 0.525 mmol) was added via syringe. The reaction was stirred at 0° C. for two hours, and then allowed to warm to room temperature and stirred overnight. After 17 hours, the reaction was quenched by slow addition of distilled water, diluted with CH2Cl2/MeOH (95:5), washed with distilled water, dried (Na2SO4) and concentrated to give a yellow oil. Purification by flash silica gel chromatography (0 to 5% MeOH in CH2Cl2) gave the titled compound as a yellow foam (80 mg). 1H NMR (300 MHz, ppm, DMSO-d6) δ 1.57-1.71 (m, 2H), 1.86-1.96 (m, 2H), 2.04-2.15 (m, 2H), 2.73 (m, 2H), 3.46-3.58 (m, 3H), 3.77 (s, 3H), 3.83 (s, 3H), 5.21 (s, 1H), 6.38 (d, J=3.1 Hz, 1H), 7.10-7.23 (m, 3H), 7.29 (d, J=3.1 Hz, 1H), 7.37 (d, J=8.4 Hz, 1H), 7.45 (s, 1H), 7.63 (d, J=2.8 Hz, 1H) MS(ESI) 418 (M+H), 416 (M−H).

Workup

  1. customto react under reductive alkylation conditions
  2. customto give a crude beige product
  3. filtrationAfter trituration of the crude product with hot ethyl acetate, filtration and concentration
  4. customthe resulting partially-purified white powder
  5. temperatureto warm to room temperature
  6. stirringstirred overnight
  7. waitAfter 17 hours
  8. customthe reaction was quenched by slow addition of distilled water
  9. additiondiluted with CH2Cl2/MeOH (95:5)
  10. washwashed with distilled water
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated
  13. customto give a yellow oil
  14. customPurification by flash silica gel chromatography (0 to 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-358b34ad8b05470f8cd034638c53d3ad
Source dataset
uspto-grants-2005_07
Patent number
US06921821B2

Reaction notes

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