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

HRID 1835588ノート

反応式

HRID 1835588 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6212Chloroform溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-0cf12d7648344f6082649067106e165d
出典データセット
uspto-grants-2004_08
特許番号
US06770666B2

反応ノート

読み込み中…