4-nitro-1H-pyrazole-3-carboxylic acid (2-amino-4,5-dimethoxy-phenyl)-amide → 5,6-Dimethoxy-2-(4-nitro-1,2-dihydro-3H-pyrazol-3-ylidene)-2H-benzimidazole

HRID 1946250Notes

Reaction equation

HRID 1946250 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=1[NH:12][C:13]([C:15]1[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][NH:17][N:16]=1)=O>C(O)(=O)C>[CH3:11][O:10][C:5]1[C:6]([O:8][CH3:9])=[CH:7][C:2]2[NH:1][C:13]([C:15]3[C:19]([N+:20]([O-:22])=[O:21])=[CH:18][NH:17][N:16]=3)=[N:12][C:3]=2[CH:4]=1

Participants

3

Reactant 1

HCID 1784932234-nitro-1H-pyrazole-3-carboxylic acid (2-amino-4,5-dimethoxy-phenyl)-amide

Product 1

HCID 1784867955,6-Dimethoxy-2-(4-nitro-1,2-dihydro-3H-pyrazol-3-ylidene)-2H-benzimidazoleYield 94%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of EDC (4.81 g 25 mmol), HOBt (3.40 g, 25 mmol) and triethylamine (4.67 g, 46 mmol) in DMF (100 ml) was added 4-nitro-1H-pyrazole-3-carboxylic acid (3.63 g, 23.09 mmol) and 4,5-dimethoxy-benzene-1,2-diamine dihydrochloride (5.06 g, 20.99 mmol) and the mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the resulting solid partitioned between EtOAc (50 ml) and saturated aqueous NaHCO3 (50 ml). A precipitate was formed and removed by filtration. The filtrate was washed with water followed by diethyl ether and then azeotroped with MeOH and toluene to yield 4-nitro-1H-pyrazole-3-carboxylic acid (2-amino-4,5-dimethoxy-phenyl)-amide (2.35 g, 36%). 4-Nitro-1H-pyrazole-3-carboxylic acid (2-amino-4,5-dimethoxy-phenyl)-amide (2.35 g, 7.65 mmol) was dissolved in acetic acid (150 ml) and refluxed at 140° C. for 5 hours. The solution was left to cool and the solvent removed in vacuo. The resulting solid was partitioned between EtOAc (25 ml) and brine (25 ml). The organic layer was separated, dried (MgSO4), filtered and the solvent removed in vacuo to yield 5,6-dimethoxy-2-(4-nitro-1H-pyrazol-3-yl)-1H-benzimidazol (2.08 g, 94%).

Workup

  1. waitThe solution was left
  2. temperatureto cool
  3. customthe solvent removed in vacuo
  4. customThe resulting solid was partitioned between EtOAc (25 ml) and brine (25 ml)
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-70a537135bd9438bb8b89da58b6f2c1a
Source dataset
uspto-grants-2013_03
Patent number
US08399442B2

Reaction notes

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