Sodium hydride → Methyl 4-{[(3,5-dichlorophenyl)(1-methyl-1H-benzimidazol-2-yl)amino]-methyl}benzoate

HRID 230010Notes

Reaction equation

HRID 230010 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[N:14]([CH3:15])[C:13]3[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=3[N:11]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[H-].[Na+].[CH3:22][O:23][C:24](=[O:33])[C:25]1[CH:30]=[CH:29][C:28]([CH2:31]Br)=[CH:27][CH:26]=1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([CH2:31][C:28]2[CH:29]=[CH:30][C:25]([C:24]([O:23][CH3:22])=[O:33])=[CH:26][CH:27]=2)[C:10]2[N:14]([CH3:15])[C:13]3[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=3[N:11]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 256687Methyl 4-(bromomethyl)benzoateHCID 923860N-(3,5-Dichlorophenyl)-1-methyl-1H-benzimidazol-2-amine

Product 1

HCID 68835443Methyl 4-{[(3,5-dichlorophenyl)(1-methyl-1H-benzimidazol-2-yl)amino]-methyl}benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the title compound from Example 223 Step A (0.21 mmol, 60 mg) and NaH (0.24 mmol, 6 mg of a 60% slurry in mineral oil) was added 0.5 mL of DMF (gas evolution). After 15 min, methyl-4-(bromomethyl)benzoate (0.24 mmol, 55 mg) was added and the reaction mixture was allowed to stand at ambient temperature overnight. The mixture was partitioned between DCM and NaHCO3. The organic phase was collected and the aqueous phase was extracted 2× with DCM. After 30 min the reaction mixture was concentrated under reduced pressure, and the residue was purified by flash chromatography on silica eluting with 2% MeOH/DCM. The product was further purified by reverse phase HPLC (Condition B). The combined HPLC fractions were neutralized with saturated NaHCO3 and extracted with DCM. The organic phase was dried over MgSO4 and concentrated under reduced pressure to afford the product as a white solid. 1H NMR (500 MHz, d6-DMSO) δ 7.94 (d, 2H), 7.68 (d, 2H), 7.61 (d, 1H), 7.52 (d, 1H), 7.21-7.29 (overlapping m, 2H), 7.10 (t, 1H), 6.79 (d, 2H), 5.27 (s, 2H), 3.83 (s, 3H), 3.50 (s, 3H). MS (ESI): m/z 440 (M+H). HPLC A: 2.16 min.

Workup

  1. waitto stand at ambient temperature overnight
  2. customThe mixture was partitioned between DCM and NaHCO3
  3. customThe organic phase was collected
  4. extractionthe aqueous phase was extracted 2× with DCM
  5. concentrationAfter 30 min the reaction mixture was concentrated under reduced pressure
  6. customthe residue was purified by flash chromatography on silica eluting with 2% MeOH/DCM
  7. customThe product was further purified by reverse phase HPLC (Condition B)
  8. extractionextracted with DCM
  9. dry with materialThe organic phase was dried over MgSO4
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-07e210d5a6b043879b6cdf83252e5917
Source dataset
uspto-grants-2009_07
Patent number
US07563815B2

Reaction notes

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