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

HRID 1946249Notes

Reaction equation

HRID 1946249 reaction equation
C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[N+:22]([C:25]1[C:26]([C:30]([OH:32])=O)=[N:27][NH:28][CH:29]=1)([O-:24])=[O:23].Cl.Cl.[CH3:35][O:36][C:37]1[CH:38]=[C:39]([NH2:46])[C:40]([NH2:45])=[CH:41][C:42]=1[O:43][CH3:44]>CN(C=O)C>[NH2:45][C:40]1[CH:41]=[C:42]([O:43][CH3:44])[C:37]([O:36][CH3:35])=[CH:38][C:39]=1[NH:46][C:30]([C:26]1[C:25]([N+:22]([O-:24])=[O:23])=[CH:29][NH:28][N:27]=1)=[O:32]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 130002194,5-Dimethoxybenzene-1,2-diamine--hydrogen chloride (1/2)HCID 178524956HCID 178524956, compound

Product 1

HCID 1784932234-nitro-1H-pyrazole-3-carboxylic acid (2-amino-4,5-dimethoxy-phenyl)-amideYield 36.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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. customThe solvent was removed in vacuo
  2. customthe resulting solid partitioned between EtOAc (50 ml) and saturated aqueous NaHCO3 (50 ml)
  3. customA precipitate was formed
  4. customremoved by filtration
  5. washThe filtrate was washed with water
  6. customazeotroped with MeOH and toluene

Sources & evidence

ORD record
ord-4d730228383a4f05a6c18a60a9fa4e4a
Source dataset
uspto-grants-2013_03
Patent number
US08399442B2

Reaction notes

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