Triphenylarsine → 1-(4-Fluoro-phenyl)-6-(3-phenyl-3H-imidazol-4-yl)-1H-benzoimidazole

HRID 2202480Notes

Reaction equation

HRID 2202480 reaction equation
[C:1]1([N:7]2[CH:11]=[CH:10][N:9]=[CH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F-].[Cs+].C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:34]1[CH:35]=[CH:36][C:37]2[N:41]=[CH:40][N:39]([C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=3)[C:38]=2[CH:49]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:48][C:45]1[CH:46]=[CH:47][C:42]([N:39]2[C:38]3[CH:49]=[C:34]([C:11]4[N:7]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)[CH:8]=[N:9][CH:10]=4)[CH:35]=[CH:36][C:37]=3[N:41]=[CH:40]2)=[CH:43][CH:44]=1

Participants

6

Reactant 4

HCID 11773TriphenylarsineHCID 25953Cesium fluorideHCID 815951-PhenylimidazoleHCID 900951396-bromo-1-(4-fluoro-phenyl)-1H-benzo[d]imidazole2×

Product 1

HCID 736719831-(4-Fluoro-phenyl)-6-(3-phenyl-3H-imidazol-4-yl)-1H-benzoimidazoleYield 19%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
140 °C

Procedure

To a flame-dried reaction flask were added commercially available 1-phenyl-1H-imidazole (50.5 mg, 0.35 mmol), palladium(II)acetate (7.86 mg, 35.0 μmol), cesium fluoride (106 mg, 0.7 mmol), triphenylarsine (21.4 mg, 70.0 μmol) and 6-bromo-1-(4-fluoro-phenyl)-1H-benzo[d]imidazole (intermediate G) (204 mg, 0.7 mmol). The reaction flask was evacuated, and backfilled with argon, and this sequence was repeated twice. Afterwards DMF (1.75 ml) was added successively under a stream of argon by syringe at room temperature. The resulting mixture was allowed to stir at 140° C. under an argon atmosphere for 48 h. Afterwards the reaction mixture was cooled to room temperature, poured into water (20 ml), extracted with ethyl acetate (2×30 ml) and washed with brine (20 ml). The combined organic layers were dried (MgSO4) and evaporated. The crude product was purified by flash chromatography on silica gel [dichloromethane/MeOH (0-3%)] and crystallization from dichloromethane/hexane to yield the title compound as an off-white solid (23 mg, 19%), MS (ISP) m/z=355.1 [(M+H)+], mp 216° C.

Workup

  1. customTo a flame-dried reaction flask
  2. customThe reaction flask was evacuated
  3. additionAfterwards DMF (1.75 ml) was added successively under a stream of argon by syringe at room temperature
  4. temperatureAfterwards the reaction mixture was cooled to room temperature
  5. additionpoured into water (20 ml)
  6. extractionextracted with ethyl acetate (2×30 ml)
  7. washwashed with brine (20 ml)
  8. dry with materialThe combined organic layers were dried (MgSO4)
  9. customevaporated
  10. customThe crude product was purified by flash chromatography on silica gel [dichloromethane/MeOH (0-3%)] and crystallization from dichloromethane/hexane

Sources & evidence

ORD record
ord-45add3f376564b04bee39b2e0e2496de
Source dataset
uspto-grants-2016_06
Patent number
US09365550B2

Reaction notes

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