Methyl iodide → N-[2-tert-Butyl-1-(cyclohexylmethyl)-1H-benzimidazol-5-yl]-N-methylacetamide

HRID 1783898Notes

Reaction equation

HRID 1783898 reaction equation
[H-].[Na+].[C:3]([C:7]1[N:11]([CH2:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C:10]2[CH:19]=[CH:20][C:21]([NH:23][C:24](=[O:26])[CH3:25])=[CH:22][C:9]=2[N:8]=1)([CH3:6])([CH3:5])[CH3:4].I[CH3:28]>C1COCC1>[C:3]([C:7]1[N:11]([CH2:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C:10]2[CH:19]=[CH:20][C:21]([N:23]([CH3:28])[C:24](=[O:26])[CH3:25])=[CH:22][C:9]=2[N:8]=1)([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 11232689N-[2-tert-butyl-1-(cyclohexylmethyl)-1H-benzimidazol-5-yl]acetamide

Product 1

HCID 11439269N-[2-tert-Butyl-1-(cyclohexylmethyl)-1H-benzimidazol-5-yl]-N-methylacetamideYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (201.5 mg, 5.04 mmol) was added to a solution of N-[2-tert-butyl-1-(cyclohexylmethyl)-1H-benzimidazol-5-yl]acetamide (549.8 mg, 1.68 mmol) (for preparation see in Example 9) in THF (50 mL) at 0° C. Stirring for 30 min., iodomethane was added. The resulting mixture was stirred overnight at room temperature and quenched with saturated NaHCO3 aqueous solution (5 mL) and water (10 mL). Two phases were separated. The aqueous was extracted with EtOAc (3×20 mL). The combined organic phases were washed with saturated NaHCO3 aqueous solution (20 mL), saturated NaCl aqueous solution (20 mL) and dried over Na2SO4. After evaporation of the solvent, the residue was purified by MPLC (EtOAc as eluent on silica gel) to give the desired title compound as a white solid (580.5 mg, 100%). 1H NMR (400 MHz, CD3OD): δ 1.26 (m, 5H), 1.67 (m, 2H), 1.69 (s, 9H), 1.71 (m, 1H), 1.78 (m, 2H), 1.87 (s, 3H), 2.14 (m, 1H), 3.30 (s, 3H), 4.49 (d, J=7.62 Hz, 2H), 7.55 (d, J=8.40 Hz, 1H), 7.71 (s, 1H), 8.00 (d, J=8.40 Hz, 1H). MS (ESI) (M+H)+: 342.3. Anal. Calcd for C21H31N3O+1.30 TFA+0.80H2O (504.14): C, 56.23; H, 6.78; N, 8.33. Found: C, 56.21; H, 6.77; N, 8.17.

Workup

  1. stirringThe resulting mixture was stirred overnight at room temperature
  2. customquenched with saturated NaHCO3 aqueous solution (5 mL) and water (10 mL)
  3. customTwo phases were separated
  4. extractionThe aqueous was extracted with EtOAc (3×20 mL)
  5. washThe combined organic phases were washed with saturated NaHCO3 aqueous solution (20 mL), saturated NaCl aqueous solution (20 mL)
  6. dry with materialdried over Na2SO4
  7. customAfter evaporation of the solvent
  8. customthe residue was purified by MPLC (EtOAc as eluent on silica gel)

Sources & evidence

ORD record
ord-5ee226211554458a9e908dd0753bfaf1
Source dataset
uspto-grants-2009_03
Patent number
US07501447B2

Reaction notes

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