Cesium carbonate → 1-isobutyl-2-amino-6-(2-(tert-butyl)-4-(4-fluorophenyl)oxazol-5-yl)-1H-benzimidazole

HRID 250776ノート

反応式

HRID 250776 の反応式
[C:1]([C:5]1[O:6][C:7](Br)=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:18]([N:22]1[C:26]2[CH:27]=[C:28](Br)[CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[NH2:32])[CH:19]([CH3:21])[CH3:20].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:18]([N:22]1[C:26]2[CH:27]=[C:28]([C:7]3[O:6][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[N:9][C:8]=3[C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)[CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[NH2:32])[CH:19]([CH3:21])[CH3:20]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 653467761-Isobutyl-2-amino-6-bromobenzimidazoleHCID 668691622-(Tert-butyl)-4-(4-fluorophenyl)-5-bromooxazole

生成物 1

HCID 668691451-isobutyl-2-amino-6-(2-(tert-butyl)-4-(4-fluorophenyl)oxazol-5-yl)-1H-benzimidazole収率 27%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

Bubble nitrogen through a suspension of 2-(tert-butyl)-4-(4-fluorophenyl)-5-bromooxazole (2.0 g, 9.1 mmol), 1-isobutyl-2-amino-6-bromobenzimidazole (4.98 g, 18.6 mmol), cesium carbonate (6.06 g, 18.6 mmol), palladium(II) acetate (0.201 g) and triphenylphosphine (1.2 g, 4.5 mmol) in 15 mL dimethylformamide for 3 minutes. Stir the reaction mixture at 100° C. for 18 hours. Cool to room temperature. Partition between ethyl acetate and saturated aqueous sodium chloride. Wash the organic layer with saturated aqueous sodium chloride, dry over sodium sulfate, and concentrate under reduced pressure. Subject the residue to silica gel chromatography, eluting with 50:1 dichloromethane:methanol containing 2M ammonium hydroxide to provide 1-isobutyl-2-amino-6-(2-(tert-butyl)-4-(4-fluorophenyl)oxazol-5-yl)-1H-benzimidazole (1 g, 27%). This material is treated with methanesulfonic acid as previously described to provide the title compound.

後処理

  1. customBubble nitrogen
  2. temperatureCool to room temperature
  3. customPartition between ethyl acetate and saturated aqueous sodium chloride
  4. washWash the organic layer with saturated aqueous sodium chloride
  5. dry with materialdry over sodium sulfate
  6. concentrationconcentrate under reduced pressure
  7. washeluting with 50:1 dichloromethane

出典と根拠

ORDレコード
ord-610419d63e6946829de96dfed4fa5133
出典データセット
uspto-grants-2011_01
特許番号
US07863310B2

反応ノート

読み込み中…