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

HRID 1760751노트

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HRID 1760751 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 3283Diethyl Ether용매

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온도
105 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-2e14448fa76d4bb1b2ce9a8940eac491
출처 데이터셋
uspto-grants-2005_01
특허 번호
US06844435B2

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