Methyl iodide → HCID 11113517, compound

HRID 1432949Notes

Reaction equation

HRID 1432949 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[C:8]([S:10]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][C:20]4[NH:28][C:27]5[CH:26]=[CH:25][N:24]=[CH:23][C:22]=5[CH:21]=4)[C:15](=[O:29])[CH2:14]3)(=[O:12])=[O:11])[S:7][C:6]=2[CH:30]=1.[H-].[Na+].[CH3:33]I>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[C:8]([S:10]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][C:20]4[N:28]([CH3:33])[C:27]5[CH:26]=[CH:25][N:24]=[CH:23][C:22]=5[CH:21]=4)[C:15](=[O:29])[CH2:14]3)(=[O:12])=[O:11])[S:7][C:6]=2[CH:30]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 11059588HCID 11059588, compound

Product 1

HCID 11113517HCID 11113517, compoundYield 50.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(6-Chlorobenzo[b]thiophene-2-sulfonyl)-1-(1H-pyrrolo[3,2-c]pyridin-2-ylmethyl)piperazin-2-one (0.59 g, 1.28 mmol), EXAMPLE 214, is dissolved in anhydrous DMF (30 ml), cooled in an ice bath, treated with 60% sodium hydride (0.061 g, 1.53 mmol) and stirred at room temperature for 30 minutes. The solution is treated with methyl iodide (83 mL, 1.33 mmol) and warmed to room temperature over 4 hours. The reaction is quenched with ammonium chloride solution, diluted with ethyl acetate and separated. The organic layer is washed with brine (3×), dried (Na2SO4) and concentrated. The residue is purified by flash chromatography (5-10% MeOH/CH2Cl2) to provide the title compound (0.31 g, 0.65 mmol). 1H NMR (CD3OD, 300 MHz) δ8.55 (d, 1H), 7.99 (dd, 1H), 7.82 (m, 3H), 7.49 (dd, 1H), 7.43 (d, 1H), 6.55 (s, 1H), 4.75 (s, 2H), 3.96 (s, 2H), 3.52 (m, 4H), 3.86 (s, 3H), 3.49 (s, 3H). Ion Spray MS, [M+H]+=477.

Workup

  1. temperaturecooled in an ice bath
  2. temperaturewarmed to room temperature over 4 hours
  3. customThe reaction is quenched with ammonium chloride solution
  4. additiondiluted with ethyl acetate
  5. customseparated
  6. washThe organic layer is washed with brine (3×)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue is purified by flash chromatography (5-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ff1ff59008eb4a10ba4e95fb43e8eb5d
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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