Sodium Carbonate → 6-(3,4-difluorophenyl)-2-(4-(3-(trifluoromethyl)pyridin-2-yl)-piperazin-1-yl)-1H-benzo[d]imidazole

HRID 912864Notes

Reaction equation

HRID 912864 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[F:8].Br[C:13]1[CH:14]=[CH:15][C:16]2[N:20]=[C:19]([N:21]3[CH2:26][CH2:25][N:24]([C:27]4[C:32]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:30]=[CH:29][N:28]=4)[CH2:23][CH2:22]3)[NH:18][C:17]=2[CH:37]=1.[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:14]=[CH:15][C:16]3[N:20]=[C:19]([N:21]4[CH2:22][CH2:23][N:24]([C:27]5[C:32]([C:33]([F:36])([F:34])[F:35])=[CH:31][CH:30]=[CH:29][N:28]=5)[CH2:25][CH2:26]4)[NH:18][C:17]=3[CH:37]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27343373,4-Difluorobenzeneboronic acidHCID 115970646-Bromo-2-[4-(3-trifluoromethylpyridin-2-yl)piperazin-1-yl]-1H-benzoimidazole

Product 1

HCID 104343296-(3,4-difluorophenyl)-2-(4-(3-(trifluoromethyl)pyridin-2-yl)-piperazin-1-yl)-1H-benzo[d]imidazole

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 3,4-difluorophenylboronic acid (111 mg, 0.7 mmol, Aldrich) and 6-bromo-2-[4-(3-trifluoromethylpyridin-2-yl)piperazin-1-yl]-1H-benzoimidazole (213 mg, 0.5 mmol, Example 23c) in ethylene glycol dimethyl ether (2 mL) were added lithium chloride (63 mg, 1.5 mmol, Aldrich) and 2M aqueous sodium carbonate (0.75 mL, 1.5 mmol). Nitrogen gas was bubbled through the mixture for 10 min and tetrakis(triphenylphosphine)palladium (58 mg, 0.05 mmol, Aldrich) was added. The reaction mixture was stirred at 80° C. under nitrogen atmosphere for 16 h, cooled to room temperature, diluted with EtOAc (50 mL) and filtered through Celite® pad. The filtrate was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (55% EtOAc/hexane) to give the title compound as a white solid. MS (ESI, pos. ion) m/z: 460.2 (M+1).

Workup

  1. customNitrogen gas was bubbled through the mixture for 10 min
  2. temperaturecooled to room temperature
  3. filtrationfiltered through Celite® pad
  4. washThe filtrate was washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography (55% EtOAc/hexane)

Sources & evidence

ORD record
ord-d96781883e2a4d4d94b742d712ef20dc
Source dataset
uspto-grants-2011_09
Patent number
US08026241B2

Reaction notes

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