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

HRID 274142Notes

Reaction equation

HRID 274142 reaction equation
[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+].[CH3:45][C:46]1[CH:51]=[CH:50][N:49]=[C:48]2[N:52]=[C:53]([CH2:55][CH2:56][CH3:57])[NH:54][C:47]=12>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:52]1[C:48]3=[N:49][CH:50]=[CH:51][C:46]([CH3:45])=[C:47]3[N:54]=[C:53]1[CH2:55][CH2:56][CH3:57])[CH:7]=[CH:6]2

Participants

8

Reactant 5

HCID 6547AzobisisobutyronitrileHCID 24758Sodium hydrideHCID 67184N-bromobutanimideHCID 150208527-Methyl-2-propyl-1H-imidazo[4,5-b]pyridineHCID 20094549ethyl 2-(3-bromo-5-methyl-2H-indazol-2-yl)benzoate

Product 1

HCID 200945323-[3-bromo-2-(2-ethoxycarbonylphenyl)-2H-indazol-5-yl]methyl-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridineYield 19.7%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 6228DimethylformamideSolvent

Procedure

Carbon tetrachloride (4 ml) was added to ethyl 2-(3-bromo-5-methyl-2H-indazol-2-yl)benzoate (0.300 g, 0.835 mmol) as obtained in Reference Example 4, and the mixture was stirred. Thereto were added N-bromosuccinimide (0.149 g, 0.835 mmol) and azobisisobutyronitrile (14 mg, 0.0835 mmol), and the mixture was refluxed under heating for 3.5 hours. After cooling, it was filtered, and the cake was washed twice with dichloromethane (2.5 ml) and the filtrate was concentrated. The residue was then dissolved in DMF (1 ml) and added to a solution obtained by adding sodium hydride (27 mg, 0.668 mmol) to 7-methyl-2-propyl-1H-imidazo[4,5-b]pyridine (0.117 g, 0.668 mmol) in DMF (2 ml) and stirring the solution for 30 minutes. The mixture was stirred at room temperature for 30 minutes, concentrated, and partitioned by ethyl acetate (5 ml) and water (5 ml). The organic layer was washed twice with water (5 ml), 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 70 mg of 3-[3-bromo-2-(2-ethoxycarbonylphenyl)-2H-indazol-5-yl]methyl-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine was obtained.

Workup

  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 twice with dichloromethane (2.5 ml)
  7. concentrationthe filtrate was concentrated
  8. dissolutionThe residue was then dissolved in DMF (1 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 (5 ml) and water (5 ml)
  15. washThe organic layer was washed twice with water (5 ml)
  16. dry with materialdried over magnesium sulfate
  17. filtrationfiltered
  18. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-e1b416a2f4ff40029d78087aa77fe0ab
Source dataset
uspto-grants-1995_02
Patent number
US05387684

Reaction notes

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