Ethylenediamine → 4-Fluoro-N-[5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-benzamide

HRID 2188811Notes

Reaction equation

HRID 2188811 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:11]=3[N:10]=[C:9]2[C:19]([F:22])([F:21])[F:20])=[N:6][CH:7]=1.[F:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([NH2:30])=[O:29])=[CH:26][CH:25]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(N)CN>O1CCOCC1.[Cu]I.CCOC(C)=O>[F:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([NH:30][C:2]2[CH:7]=[N:6][C:5]([N:8]3[C:12]4[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:11]=4[N:10]=[C:9]3[C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=2)=[O:29])=[CH:26][CH:25]=1

Participants

8

Reactant 4

HCID 3301EthylenediamineHCID 62657Potassium Phosphate, TribasicHCID 715724-FluorobenzamideHCID 573569041-(5-Bromopyrazin-2-YL)-2-(trifluoromethyl)-5-methoxy-1H-benzo[D]imidazole

Product 1

HCID 589938444-Fluoro-N-[5-(5-methoxy-2-trifluoromethyl-benzoimidazol-1-yl)-pyrazin-2-yl]-benzamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Into a 50 mL 3-necked round bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1-(5-bromo-pyrazin-2-yl)-5-methoxy-2-trifluoromethyl-1H-benzoimidazole (iv) (100 mg, 0.27 mmol) in 1,4-dioxane (30 mL). To this was added 4-fluorobenzamide (80 mg, 0.58 mmol), K3PO4 (250 mg, 1.18 mmol), CuI (10 mg, 0.05 mmol) and ethane-1,2-diamine (EDA) (5 mg, 0.08 mmol). The resulting solution was stirred at reflux overnight. The reaction progress was monitored by TLC (EtOAc/PE=1:2). When the reaction had gone to completion, the mixture was filtered to remove the solid components, then concentrated under vacuum. The residue was dissolved in EtOAc, then washed with water. The organic layer was dried over Na2SO4, then concentrated to yield a crude product.

Workup

  1. customInto a 50 mL 3-necked round bottom flask, purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperatureat reflux overnight
  4. filtrationthe mixture was filtered
  5. customto remove the solid components
  6. concentrationconcentrated under vacuum
  7. dissolutionThe residue was dissolved in EtOAc
  8. washwashed with water
  9. dry with materialThe organic layer was dried over Na2SO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-e1af3749b2cd4a9f93382253b34a2f61
Source dataset
uspto-grants-2012_12
Patent number
US08324219B2

Reaction notes

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