Potassium Carbonate → Methyl [1-(2,4-dichlorophenyl)-5-(diethylamino)-2,3-dihydro-1H-imidazo[1,2-a]benzimidazol-2-yl]acetate

HRID 1399013Notes

Reaction equation

HRID 1399013 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:14]([CH2:15][CH:16](O)[CH2:17][C:18]([O:20][CH3:21])=[O:19])[C:13]2[C:23]([N:27]([CH2:30][CH3:31])[CH2:28][CH3:29])=[CH:24][CH:25]=[CH:26][C:12]=2[N:11]=1.CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1.C(=O)([O-])O.[Na+].C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:10]2=[N:11][C:12]3[CH:26]=[CH:25][CH:24]=[C:23]([N:27]([CH2:30][CH3:31])[CH2:28][CH3:29])[C:13]=3[N:14]2[CH2:15][CH:16]1[CH2:17][C:18]([O:20][CH3:21])=[O:19]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 68765145Methyl 4-[2-[(2,4-dichlorophenyl)amino]-7-(diethylamino)-1H-benzimidazol-1-yl]-3-hydroxybutanoate

Product 1

HCID 57785854Methyl [1-(2,4-dichlorophenyl)-5-(diethylamino)-2,3-dihydro-1H-imidazo[1,2-a]benzimidazol-2-yl]acetateYield 84.2%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of methyl 4-[2-[(2,4-dichlorophenyl)amino]-7-(diethylamino)-1H-benzimidazol-1-yl]-3-hydroxybutanoate (Reference Example 83; 200 mg, 0.430 mmol) in pyridine (4 mL) was added methanesulfonyl chloride (0.166 mL, 2.14 mmol) at 0° C. After the resultant mixture was stirred at room temperature for 16 hr, the mixture was diluted with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting mesylate was diluted with N,N-dimethylformamide (9 mL) and to the solution was added potassium carbonate (119 mg, 0.862 mmol) at room temperature. After the resultant mixture was stirred at 80° C. for 2 hr, the mixture was diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 10-50% ethyl acetate/n-hexane gradient mixture to give the title compound as a solid (162 mg, 0.362 mmol, 84%). Analytically pure material was obtained by recrystallization from ethyl acetate/n-hexane.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. additionThe resulting mesylate was diluted with N,N-dimethylformamide (9 mL) and to the solution
  7. washwashed with water and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash column chromatography on silica gel eluting with a 10-50% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-a0ef12d34b484d5292b5ad8ba9f09034
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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