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

HRID 250776Notes

Reaction equation

HRID 250776 reaction equation
[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]

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-610419d63e6946829de96dfed4fa5133
Source dataset
uspto-grants-2011_01
Patent number
US07863310B2

Reaction notes

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