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

HRID 250776노트

반응식

HRID 250776 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-610419d63e6946829de96dfed4fa5133
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863310B2

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