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

HRID 2296716ノート

反応式

HRID 2296716 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒

反応条件

温度
105 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-5d4b203366f342d083400743e3caf75b
出典データセット
uspto-grants-2002_12
特許番号
US06489328B2

反応ノート

読み込み中…