Water → HCID 18426817, compound

HRID 1281161Notes

Reaction equation

HRID 1281161 reaction equation
[Cl:1][C:2]1[C:31]([Cl:32])=[CH:30][C:5]2[N:6]=[C:7]([C:9]3[N:10](S(C4C=CC(C)=CC=4)(=O)=O)[C:11]4[C:16]([CH:17]=3)=[CH:15][C:14]([CH:18]=[O:19])=[CH:13][CH:12]=4)[NH:8][C:4]=2[CH:3]=1.C(N(C(C)C)CC)(C)C.[CH3:42][O:43][CH2:44]Cl.O>CN(C)C=O>[Cl:32][C:31]1[C:2]([Cl:1])=[CH:3][C:4]2[N:8]([CH2:42][O:43][CH3:44])[C:7]([C:9]3[NH:10][C:11]4[C:16]([CH:17]=3)=[CH:15][C:14]([CH:18]=[O:19])=[CH:13][CH:12]=4)=[N:6][C:5]=2[CH:30]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 18426790HCID 18426790, compound

Product 1

HCID 18426817HCID 18426817, compoundYield 89.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5,6-dichloro-2-[5-formyl-1-(4-methylphenyl)sulfonylindol-2-yl]benzimidazole obtained in Example 45 (824 mg, 1.71 mmol) in dimethylformamide (10 mL) were added diisopropylethylamine (0.59 mL, 3.4 mmol) and chloromethyl methyl ether (0.16 mL, 2.1 mmol), and the mixture was stirred at room temperature for 15 h. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue were added methanol (80 mL) and 2 mol/L sodium hydroxide (5 mL), and the mixture was heated to reflux for 1 h. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was triturated with ether to afford 5,6-dichloro-2-[5-formylindol-2-yl]-1-(methoxymethyl)benzimidazole (570 mg, 89%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried on anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. additionTo the residue were added methanol (80 mL) and 2 mol/L sodium hydroxide (5 mL)
  6. temperaturethe mixture was heated
  7. temperatureto reflux for 1 h
  8. additionWater was added
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe organic layer was washed with water and brine
  11. dry with materialdried on anhydrous sodium sulfate
  12. customThe solvent was removed under reduced pressure
  13. customthe residue was triturated with ether

Sources & evidence

ORD record
ord-caa7351e185a4a66977440b6cfaf3b60
Source dataset
uspto-grants-2002_09
Patent number
US06452014B1

Reaction notes

Loading…