4-Methylpyrazole → 4-Bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-5-(4-methyl-pyrazol-1-ylmethyl)-1H-benzoimidazole

HRID 1661936Notes

Reaction equation

HRID 1661936 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:5]=[N:6][NH:7][CH:8]=1.[Br:9][C:10]1[C:18]2[N:17]=[C:16]([C:19]3[CH:24]=[CH:23][C:22]([CH:25]([CH3:27])[CH3:26])=[CH:21][CH:20]=3)[N:15]([CH2:28][CH2:29][O:30][CH3:31])[C:14]=2[C:13]([O:32][CH3:33])=[CH:12][C:11]=1[CH2:34]OS(C)(=O)=O>CN(C=O)C>[Br:9][C:10]1[C:18]2[N:17]=[C:16]([C:19]3[CH:20]=[CH:21][C:22]([CH:25]([CH3:27])[CH3:26])=[CH:23][CH:24]=3)[N:15]([CH2:28][CH2:29][O:30][CH3:31])[C:14]=2[C:13]([O:32][CH3:33])=[CH:12][C:11]=1[CH2:34][N:6]1[CH:5]=[C:4]([CH3:3])[CH:8]=[N:7]1

Participants

5

Reactant 3

HCID 34064-MethylpyrazoleHCID 24758Sodium hydrideHCID 57771995methanesulfonic acid 4-bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazol-5-ylmethyl ester

Product 1

HCID 113864244-Bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-5-(4-methyl-pyrazol-1-ylmethyl)-1H-benzoimidazoleYield 69.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (7 mg, 0.3 mmol) is added to a solution of 23 μl (0.30 mmol) 4-methylpyrazole in 2 ml DMF. The resulting mixture is stirred at room temperature for 1 h, then 119 mg (0.23 mmol) methanesulfonic acid 4-bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazol-5-ylmethyl ester is added. Stirring is continued for 20 h. After that the reaction mixture is poured on water and extracted (3×) with ethyl acetate. The combined organic layers are washed with water (2×) and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by flash-chromatography on silica gel (dichloromethane:isopropanol=95:5) to afford 80 mg of the title compound as a white foam.

Workup

  1. stirringStirring
  2. waitis continued for 20 h
  3. additionAfter that the reaction mixture is poured on water
  4. extractionextracted (3×) with ethyl acetate
  5. washThe combined organic layers are washed with water (2×) and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by flash-chromatography on silica gel (dichloromethane:isopropanol=95:5)

Sources & evidence

ORD record
ord-d68ca47f16b346a2a470a1991cb5b985
Source dataset
uspto-grants-2011_10
Patent number
US08030497B2

Reaction notes

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