Methyl iodide → HCID 23546175, compound

HRID 8116Notes

Reaction equation

HRID 8116 reaction equation
[H-].[Na+].[CH2:3]([N:10]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C@H:11]([CH3:24])[CH2:12][C:13]1[C:21]2[C:16](=[C:17]([F:23])[CH:18]=[C:19]([F:22])[CH:20]=2)[NH:15][CH:14]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.I[CH3:33]>CN(C)C=O>[CH2:25]([N:10]([CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[C@H:11]([CH3:24])[CH2:12][C:13]1[C:21]2[C:16](=[C:17]([F:23])[CH:18]=[C:19]([F:22])[CH:20]=2)[N:15]([CH3:33])[CH:14]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 20806554dibenzyl-[2-(5,7-difluoro-1H-indol-3-yl)-1(R)-methyl-ethyl]-amine

Product 1

HCID 23546175HCID 23546175, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

NaH (180 mg of 60% oil dispersion, 4.5 mmol) is added to a solution of dibenzyl-[2-(5,7-difluoro-1H-indol-3-yl)-1(R)-methyl-ethyl]-amine (1.4 g, 3.6 mmol) in 20 ml dimethylformamide under N2 at 0° C. The resulting mixture is stirred for 20 minutes, then is allowed to warm to room temperature over 20 minutes. A 5 ml solution of iodomethane in dimethylformamide (7.2 mmol) is added dropwise and the reaction mixture is stirred for 1 hour. The reaction is quenched with cold aqueous NaHCO3, extracted with ethyl acetate, washed with brine, dried (Na2SO4), filtered, concentrated and is purified by flash chromatography (SiO2, ethyl acetate/hexane gradient) to yield 1.3 g of dibenzyl-[2-(5,7-difluoro-1-methyl-1H-indol-3-yl)-1(R)-methyl-ethyl]-amine (89%).

Workup

  1. stirringthe reaction mixture is stirred for 1 hour
  2. customThe reaction is quenched with cold aqueous NaHCO3
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customis purified by flash chromatography (SiO2, ethyl acetate/hexane gradient)

Sources & evidence

ORD record
ord-825e0f147af6474489eb0897d71af069
Source dataset
uspto-grants-2006_08
Patent number
US07087635B2

Reaction notes

Loading…