Sulfuric Acid → 5-Amino-2-(2,6-dichlorophenylamino)-3-methyl-3H-benzoimidazole-4-carboxylic acid amide

HRID 2296716Notes

Reaction equation

HRID 2296716 reaction equation
[NH2:1][C:2]1[CH:20]=[CH:19][C:5]2[N:6]=[C:7]([NH:10][C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:8]([CH3:9])[C:4]=2[C:3]=1[C:21]#[N:22].[OH:23]S(O)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>CCOCC>[NH2:1][C:2]1[CH:20]=[CH:19][C:5]2[N:6]=[C:7]([NH:10][C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:8]([CH3:9])[C:4]=2[C:3]=1[C:21]([NH2:22])=[O:23]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 225967045-Amino-3-methyl-2-(2,6-dichlorophenylamino)-3h-benzimidazole-4-carbonitrile

Product 1

HCID 113939665-Amino-2-(2,6-dichlorophenylamino)-3-methyl-3H-benzoimidazole-4-carboxylic acid amideYield 66%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 5-amino-3-methyl-2-(2,6-dichlorophenylamino)-3H-benzimidazole-4-carbonitrile (Example 6) (1 g, 3 mmol) and conc. H2SO4 (8 mL) was warmed to 100-110° C. for 1 h and monitored by TLC for the disappearance of starting material. The mixture was cooled and poured onto a mixture of crushed ice, sodium carbonate, and ether. The precipitate was filtered, washed with water, dissolved in MeOH-methylene chloride, treated with carbon (decolorizing charcoal), dried (MgSO4), filtered, and concentrated in vacuo. The aqueous filtrate was washed with EtOAc (3×30 mL). The combined organic layers were washed with brine (25 mL), which was then extracted with EtOAc (20 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated to yield 190 mg of a crude product. This was combined with the solid product and triturated with ether-methylene chloride to afford 5-amino-2-(2,6-dichlorophenylamino)-3-methyl-3H-benzoimidazole-4-carboxylic acid amide (700 mg, 66%). The filtrate was chromatographed on silica gel to afford an additional 128 mg (12%) of product.

Workup

  1. temperatureThe mixture was cooled
  2. filtrationThe precipitate was filtered
  3. washwashed with water
  4. dissolutiondissolved in MeOH-methylene chloride
  5. additiontreated with carbon (decolorizing charcoal)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. washThe aqueous filtrate was washed with EtOAc (3×30 mL)
  10. washThe combined organic layers were washed with brine (25 mL), which
  11. extractionwas then extracted with EtOAc (20 mL)
  12. dry with materialThe combined organic layers were dried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto yield 190 mg of a crude product
  16. customtriturated with ether-methylene chloride

Sources & evidence

ORD record
ord-5d4b203366f342d083400743e3caf75b
Source dataset
uspto-grants-2002_12
Patent number
US06489328B2

Reaction notes

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