Methyl iodide → [1-(3,5-difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-yl]-methyl-amine

HRID 1158838Notes

Reaction equation

HRID 1158838 reaction equation
IC.[F:3][C:4]1[CH:5]=[C:6]([CH:28]=[C:29]([F:31])[CH:30]=1)[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([NH2:17])[CH:15]=2)[C:10]([S:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[N+:25]([O-:27])=[O:26])=[CH:9]1.[C:32](=O)([O-])[O-].[Na+].[Na+]>C(O)C.O1CCCC1>[F:3][C:4]1[CH:5]=[C:6]([CH:28]=[C:29]([F:31])[CH:30]=1)[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([NH:17][CH3:32])[CH:15]=2)[C:10]([S:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[N+:25]([O-:27])=[O:26])=[CH:9]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 10340Sodium CarbonateHCID 594638551-(3,5-Difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-ylamine

Product 1

HCID 66842175[1-(3,5-difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-yl]-methyl-amineYield 25%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Iodomethane (0.568 ml, 9.12 mmol) was added to a solution of 1-(3,5-difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-ylamine (Example 15a; 2.5 g, 6.1 mmol) in a mixture of ethanol and tetrahydrofuran containing sodium carbonate (0.657 g, 6.08 mmol). The reaction mixture was heated under reflux overnight and concentrated. Water was added and the product was extracted into ethyl acetate. The combined organic phases were washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. Column chromatography (heptane/ethyl acetate 8:2) afforded [1-(3,5-difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-yl]-methyl-amine (0.647 g) and [1-(3,5-difluoro-benzyl-3-(2-nitro-phenylsulfanyl)-1H-indol-6-yl]-dimethyl-amine (0.815 g). 1H-NMR (CDCl3) δ 8.26 (dd, 1H, J=8.2 and 1.2 Hz), 7.35 (d, 1H, J=8.6 Hz), 7.27 (ddd, 1H, J=8.2, 7.4 and 1.2 Hz), 7.25 (s, 1H), 7.17 (ddd, 1H, J=8.2, 7.4 and 1.2 Hz), 7.03 (dd, 1H, J=8.2 and 1.2 Hz), 6.78 (dd, 1H, J=8.6 and 2.3 Hz), 6.74 (tt, 1H, J=8.6 and 2.3 Hz), 6.68 (m, 2H), 6.48 (d, 1H, J=2.3 Hz), 5.29 (s, 2H), 2.95 (s, 6H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux overnight
  3. concentrationconcentrated
  4. additionWater was added
  5. extractionthe product was extracted into ethyl acetate
  6. washThe combined organic phases were washed with water and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6c0a7f08295f4cee86c4cf8e5c9ca6bd
Source dataset
uspto-grants-2010_10
Patent number
US07812036B2

Reaction notes

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