Azobisisobutyronitrile → 3-[3-bromo-2-(2-ethoxycarbonylphenyl)-2H-indazol-5-yl]methyl-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine

HRID 274141ノート

反応式

HRID 274141 の反応式
[Br:1][C:2]1[N:3]([C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])[N:4]=[C:5]2[C:10]=1[CH:9]=[C:8]([CH3:11])[CH:7]=[CH:6]2.BrN1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N.[H-].[Na+].[CH2:45]([C:47]1[NH:48][C:49]2[C:50]([N:57]=1)=[N:51][C:52]([CH3:56])=[CH:53][C:54]=2[CH3:55])[CH3:46]>CN(C=O)C.C(Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[N:3]([C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])[N:4]=[C:5]2[C:10]=1[CH:9]=[C:8]([CH2:11][N:57]1[C:50]3=[N:51][C:52]([CH3:56])=[CH:53][C:54]([CH3:55])=[C:49]3[N:48]=[C:47]1[CH2:45][CH3:46])[CH:7]=[CH:6]2

参加物

8

反応物 5

HCID 6547AzobisisobutyronitrileHCID 24758Sodium hydrideHCID 67184N-bromobutanimideHCID 98153742,6-Dimethyl-8-ethyl-1-deazapurineHCID 20094549ethyl 2-(3-bromo-5-methyl-2H-indazol-2-yl)benzoate

生成物 1

HCID 200945583-[3-bromo-2-(2-ethoxycarbonylphenyl)-2H-indazol-5-yl]methyl-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine収率 33.1%

試薬・触媒・溶媒 2

HCID 5943Carbon Tetrachloride溶媒HCID 6228Dimethylformamide溶媒

実験手順

Carbon tetrachloride (2 ml) was added to ethyl 2-(3-bromo-5-methyl-2H-indazol-2-yl)benzoate (0.450 g, 1.25 mmol) as obtained in Reference Example 4, and the mixture was stirred. Thereto were added N-bromosuccinimide (0.223 g, 1.25 mmol) and azobisisobutyronitrile (21 mg, 0.125 mmol), and the mixture was refluxed under heating for 3.5 hours. After cooling, it was filtered, and the cake was washed with dichloromethane (2 ml) and the filtrate was concentrated. The residue was then dissolved in DMF (2 ml), and added to a solution obtained by adding sodium hydride (40 mg, 1.00 mmol) to 2-ethyl-5,7-dimethyl-1H-imidazo[4,5-b]pyridine (0.176 mg, 1.00 mmol) in DMF (4 ml) and stirring the solution for 30 minutes. The mixture was stirred at room temperature for 30 minutes, concentrated, and partitioned by ethyl acetate (10 ml) and water (10 ml). The organic layer was dried over magnesium sulfate, and then filtered. The filtrate was concentrated and subjected to flash chromatography on silica gel using a mixed solvent of hexane/ethyl acetate (2:3), whereby 0.176 g of 3-[3-bromo-2-(2-ethoxycarbonylphenyl)-2H-indazol-5-yl]methyl-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine was obtained.

後処理

  1. customas obtained in Reference Example 4
  2. temperaturethe mixture was refluxed
  3. temperatureunder heating for 3.5 hours
  4. temperatureAfter cooling
  5. filtrationit was filtered
  6. washthe cake was washed with dichloromethane (2 ml)
  7. concentrationthe filtrate was concentrated
  8. dissolutionThe residue was then dissolved in DMF (2 ml)
  9. additionadded to a solution
  10. customobtained
  11. stirringstirring the solution for 30 minutes
  12. stirringThe mixture was stirred at room temperature for 30 minutes
  13. concentrationconcentrated
  14. custompartitioned by ethyl acetate (10 ml) and water (10 ml)
  15. dry with materialThe organic layer was dried over magnesium sulfate
  16. filtrationfiltered
  17. concentrationThe filtrate was concentrated

出典と根拠

ORDレコード
ord-7c5c10aadbe249f4b48b7ae2a5ba5e74
出典データセット
uspto-grants-1995_02
特許番号
US05387684

反応ノート

読み込み中…