Water → Methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

HRID 2216711Notes

Reaction equation

HRID 2216711 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=2)=[C:6]([CH:35]=1)[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[C:18]3[CH:26]=[CH:27][C:28]([C:30]([O:32][CH3:33])=[O:31])=[CH:29][C:17]=3[N:16]=2)=[C:11]([F:34])[CH:10]=1.C(N(CC)CC)C.Cl[CH2:51][CH2:52][CH2:53][C:54](Cl)=[O:55].O>C(Cl)(Cl)Cl>[Cl:42][C:39]1[CH:40]=[CH:41][C:36]([C:5]2[CH:4]=[CH:3][C:2]([N:1]3[CH2:51][CH2:52][CH2:53][C:54]3=[O:55])=[CH:35][C:6]=2[CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:19]([CH:20]4[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]4)[C:18]4[CH:26]=[CH:27][C:28]([C:30]([O:32][CH3:33])=[O:31])=[CH:29][C:17]=4[N:16]=3)=[C:11]([F:34])[CH:10]=2)=[CH:37][CH:38]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 783704-Chlorobutyryl chlorideHCID 21943052Methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate

Product 1

HCID 11846338Methyl 2-[4-{2-(4-chlorophenyl)-5-(2-oxopyrrolidin-1-yl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Methyl 2-[4-{5-amino-2-(4-chlorophenyl)benzyloxy}-2-fluorophenyl]-1-cyclohexylbenzimidazole-5-carboxylate (500 mg) obtained in Example 338 and triethylamine (0.14 ml) were dissolved in chloroform (5 ml), and commercially available chlorobutyryl chloride (0.1 ml) was added under ice-cooling, which was followed by stirring at room temperature for 3 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dimethylformamide (6 ml) and potassium carbonate (244 mg) was added, which was followed by stirring at 80° C. for 1 hr. The reaction mixture was allowed to cool, water was added and the precipitated crystals were collected by filtration to give the title compound (502 mg, yield 89%).

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in dimethylformamide (6 ml)
  7. additionpotassium carbonate (244 mg) was added
  8. stirringby stirring at 80° C. for 1 hr
  9. temperatureto cool
  10. additionwater was added
  11. filtrationthe precipitated crystals were collected by filtration

Sources & evidence

ORD record
ord-c020f7ab97e04904a72e567f8896679d
Source dataset
uspto-grants-2006_09
Patent number
US07112600B1

Reaction notes

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