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

HRID 1181334Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1181334
[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

Komponenten

6

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6212ChloroformLösungsmittel

Versuchsvorschrift

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%).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-1d718967f4c645eb920457565516586c
Quelldatensatz
uspto-grants-2007_10
Patentnummer
US07285551B2

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