Triphenylarsine → 3-(4-Fluoro-phenyl)-6-[3-(4-fluoro-phenyl)-3H-imidazol-4-yl]-imidazol[1,2-a]pyridine

HRID 629284Notes

Reaction equation

HRID 629284 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[CH:11][N:10]=[CH:9]2)=[CH:4][CH:3]=1.[F-].[Cs+].C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:35]1[CH:36]=[CH:37][C:38]2[N:39]([C:41]([C:44]3[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=3)=[CH:42][N:43]=2)[CH:40]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.CN(C=O)C>[F:50][C:47]1[CH:46]=[CH:45][C:44]([C:41]2[N:39]3[CH:40]=[C:35]([C:12]4[N:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[CH:9]=[N:10][CH:11]=4)[CH:36]=[CH:37][C:38]3=[N:43][CH:42]=2)=[CH:49][CH:48]=1

Participants

8

Reactant 4

HCID 11773TriphenylarsineHCID 25953Cesium fluorideHCID 1408331-(4-Fluorophenyl)imidazoleHCID 901891376-Bromo-3-(4-fluorophenyl)-imidazo[1,2-a]pyridine2×

Product 1

HCID 760725273-(4-Fluoro-phenyl)-6-[3-(4-fluoro-phenyl)-3H-imidazol-4-yl]-imidazol[1,2-a]pyridineYield 31.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a flame-dried reaction flask were added at room temperature and under an argon atmosphere commercially available 1-(4-fluorophenyl)-1H-imidazole (69.6 mg, 429 μmol), palladium(II)acetate (9.64 mg, 42.9 μmol), cesium fluoride (130 mg, 859 μmol), triphenylarsine (26.3 mg, 85.9 μmol) and 6-bromo-3-(4-fluoro-phenyl)-imidazo[1,2-a]pyridine (intermediate E) (125 mg, 429 μmol). Afterwards DMF (2.15 ml) was added successively by syringe at room temperature and under a stream of argon. The resulting mixture was allowed to stir at 140° C. under an argon atmosphere for 24 h. The reaction mixture was cooled to room temperature, water (10 ml) was added and the mixture was extracted with dichloromethane (2×40 ml). The combined organic layers were washed with water (2×20 ml), dried (MgSO4) and evaporated. The crude product was purified by flash chromatography on silica gel (dichloromethane/MeOH, 2-8%) and crystallization (dichloromethane/heptane) to yield the title compound as an off-white solid (50 mg, 31%), MS (ISP) m/z=373.4 [(M+H)+], mp 206° C.

Workup

  1. customTo a flame-dried reaction flask
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionthe mixture was extracted with dichloromethane (2×40 ml)
  4. washThe combined organic layers were washed with water (2×20 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe crude product was purified by flash chromatography on silica gel (dichloromethane/MeOH, 2-8%) and crystallization (dichloromethane/heptane)

Sources & evidence

ORD record
ord-15c3b4fbc303407ebcb6485b912b80e4
Source dataset
uspto-grants-2016_04
Patent number
US09315502B2

Reaction notes

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