Water → 2-methyl-4-[(methyloxy)methyl]-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole

HRID 44562Notes

Reaction equation

HRID 44562 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[C:9]=2[CH3:18])[C:5]2[CH:19]=[C:20]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:21]=[C:22]([CH2:23][OH:24])[C:4]=2[N:3]=1.[H-].[Na+].[CH3:33]I.O>CN(C)C=O>[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:17])[F:16])[C:9]=2[CH3:18])[C:5]2[CH:19]=[C:20]([N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[CH:21]=[C:22]([CH2:23][O:24][CH3:33])[C:4]=2[N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 56960404[2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazol-4-yl]methanol

Product 1

HCID 569609602-methyl-4-[(methyloxy)methyl]-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the mixture of [2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazol-4-yl]methanol, prepared as described in Example 43 (160 mg, 0.381 mmol) in N,N-Dimethylformamide (DMF) (15 mL), sodium hydride (30.5 mg, 0.763 mmol) was added in and followed by the addition of methyl iodide (0.048 mL, 0.763 mmol). The reaction was stirred at rt for 3 hours. More sodium hydride (30.5 mg, 0.763 mmol) and methyl iodide (0.048 mL, 0.763 mmol) was added in. The reaction was stirred at rt for another 2 hours then Water (70 mL) was added in. The mixture was extracted with EtOAc (100 mL). The organic phase was washed with Brine (100 mL), dried (MgSO4) and concentrated. The crude was subjected to ISCO purification (0˜2% MeOH/DCM) to give the product. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.36 (s, 3H) 2.54 (s, 3H) 3.00-3.07 (m, 4H) 3.37 (s, 3H) 3.68-3.75 (m, 4H) 4.76 (s, 2H) 5.52 (s, 2H) 6.32 (d, J=7.83 Hz, 1H) 6.88 (m, 2H) 7.25 (s, 1H) 7.60 (d, 1H). MS (ES+) m/e 434.4 [M+H]+.

Workup

  1. customprepared
  2. additionwas added in and
  3. stirringThe reaction was stirred at rt for another 2 hours
  4. extractionThe mixture was extracted with EtOAc (100 mL)
  5. washThe organic phase was washed with Brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe crude was subjected to ISCO purification (0˜2% MeOH/DCM)
  9. customto give the product

Sources & evidence

ORD record
ord-edf9c1027e444b478ab8d815b17d89a9
Source dataset
uspto-grants-2013_09
Patent number
US08541411B2

Reaction notes

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