Sodium Iodide → 6-Bromo-1-(2-dimethylamino-ethyl)-1H-indole-3-carboxylic acid methyl ester

HRID 250234Notes

Reaction equation

HRID 250234 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Br:14])=[CH:11][CH:12]=2)[NH:7][CH:6]=1)=[O:4].[H-].[Na+].[I-].[Na+].Cl.[CH3:20][N:21]([CH3:25])[CH2:22][CH2:23]Cl>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Br:14])=[CH:11][CH:12]=2)[N:7]([CH2:23][CH2:22][N:21]([CH3:25])[CH3:20])[CH:6]=1)=[O:4]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 11499811Methyl 6-Bromo-1H-Indole-3-CarboxylateHCID 11636816N,N-Dimethylaminoethyl chloride hydrochloride

Product 1

HCID 672715196-Bromo-1-(2-dimethylamino-ethyl)-1H-indole-3-carboxylic acid methyl esterYield 30.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-bromo-1H-indole-3-carboxylic acid methyl ester (500 mg, 1.97 mmol), sodium hydride (60% in mineral oil, 748 mg, 31.2 mmol), sodium iodide (295 mg, 1.96 mmol), 2-dimethylaminoethyl chloride hydrochloride (341 mg, 2.37 mmol) and DMF (60 mL) is heated at 100° C. for 8 hours. The reaction mixture is cooled, filtered, and the solids are washed with water and air dried. The solids are dissolved in MeOH (200 mL) and (trimethylsilyl)diazomethane (2.0 M solution in hexanes, 20 mL) is added over several minutes. The reaction mixture is stirred for one hour and concentrated under reduced pressure. The residue is partitioned between water and ethyl acetate. The ethyl acetate layer is separated and dried over MgSO4. The crude product is purified via radial chromatography using 2.5% MeOH/CH2Cl2 to afford the title compound (195 mg, 30%). ES/MS m/e 327.0 (M+2).

Workup

  1. temperatureThe reaction mixture is cooled
  2. filtrationfiltered
  3. washthe solids are washed with water and air
  4. customdried
  5. dissolutionThe solids are dissolved in MeOH (200 mL)
  6. addition(trimethylsilyl)diazomethane (2.0 M solution in hexanes, 20 mL) is added over several minutes
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is partitioned between water and ethyl acetate
  9. customThe ethyl acetate layer is separated
  10. dry with materialdried over MgSO4
  11. customThe crude product is purified via radial chromatography

Sources & evidence

ORD record
ord-cf9ac4e051584999a559b31c622d4c49
Source dataset
uspto-grants-2011_01
Patent number
US07863302B2

Reaction notes

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