Dichloromethane → 3-{[3-bromo-2-[3-chloro-2-(2-(triphenylmethyl)-2H-tetrazol-5-yl)phenyl]-2H-indazol-5-yl]methyl}-2-ethyl-5, 7-dimethyl-3H-imidazo[4,5-b]pyridine

HRID 274146Notes

Reaction equation

HRID 274146 reaction equation
Cl[C:2]1[C:3]([N:32]2[CH:40]=[C:39]3[C:34]([CH:35]=[CH:36][C:37]([CH3:41])=[CH:38]3)=[N:33]2)=[C:4]([C:8]2[N:9]=[N:10][N:11]([C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:12]=2)C=[CH:6][CH:7]=1.[Br:42]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N.[H-].[Na+].[CH2:64]([C:66]1[NH:67][C:68]2[C:69]([N:76]=1)=[N:70][C:71]([CH3:75])=[CH:72][C:73]=2[CH3:74])[CH3:65].Cl[CH2:78][Cl:79]>CN(C=O)C.O.C(Cl)(Cl)(Cl)Cl>[Br:42][C:40]1[N:32]([C:3]2[CH:2]=[CH:7][CH:6]=[C:78]([Cl:79])[C:4]=2[C:8]2[N:9]=[N:10][N:11]([C:13]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:12]=2)[N:33]=[C:34]2[C:39]=1[CH:38]=[C:37]([CH2:41][N:76]1[C:69]3=[N:70][C:71]([CH3:75])=[CH:72][C:73]([CH3:74])=[C:68]3[N:67]=[C:66]1[CH2:64][CH3:65])[CH:36]=[CH:35]2

Participants

10

Reactant 6

HCID 6344DichloromethaneHCID 6547AzobisisobutyronitrileHCID 24758Sodium hydrideHCID 67184N-bromobutanimide2×HCID 98153742,6-Dimethyl-8-ethyl-1-deazapurineHCID 200945175-[3-chloro-2-[5-methyl-2H-indazol-2-yl)phenyl]-2-(triphenylmethyl)-2H-tetrazole

Product 1

HCID 200945383-{[3-bromo-2-[3-chloro-2-(2-(triphenylmethyl)-2H-tetrazol-5-yl)phenyl]-2H-indazol-5-yl]methyl}-2-ethyl-5, 7-dimethyl-3H-imidazo[4,5-b]pyridine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 5943Carbon TetrachlorideSolventHCID 6228DimethylformamideSolvent

Procedure

Carbon tetrachloride (40 ml) was added to 5-[3-chloro-2-[5-methyl-2H-indazol-2-yl)phenyl]-2-(triphenylmethyl)-2H-tetrazole (4.0 g, 7.23 mmol) as obtained in Reference Example 16, and the mixture was stirred. Thereto were added N-bromosuccinimide (1.42 g, 7.96 mmol), and the mixture was refluxed under heating for an hour. Thereto were added N-bromosuccinimide (1.22 g, 6.89 mmol) and azobisisobutyronitrile (57 mg, 0.345 mmol), and the mixture was refluxed under heating for 2.5 hours. After cooling, the mixture was diluted with dichloromethane (40 ml), and poured into water (40 ml). The organic layer was dried over magnesium sulfate, filtered, and concentrated. The residue was dried in vacuo. The residue thus obtained was added to a solution obtained by adding, in a different reaction vessel, sodium hydride (0.257 g, 5.88 mmol) to 2-ethyl-5,7-dimethyl-1H-imidazo[4,5-b]pyridine (1.03 g, 5.88 mmol) in DMF (39 ml) and stirring the solution for 30 minutes. The mixture was stirred at room temperature for 15 hours, concentrated, and partitioned by ethyl acetate (100 ml) and water (100 ml). The water layer was extracted with ethyl acetate (100 ml) and then with dichloromethane (100 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 0.992 g of 3-{[3-bromo-2-[3-chloro-2-(2-(triphenylmethyl)-2H-tetrazol-5-yl)phenyl]-2H-indazol-5-yl]methyl}-2-ethyl-5, 7-dimethyl-3H-imidazo[4,5-b]pyridine was obtained.

Workup

  1. customas obtained in Reference Example 16
  2. temperaturethe mixture was refluxed
  3. temperatureunder heating for an hour
  4. temperaturethe mixture was refluxed
  5. temperatureunder heating for 2.5 hours
  6. temperatureAfter cooling
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was dried in vacuo
  11. customThe residue thus obtained
  12. additionwas added to a solution
  13. customobtained
  14. additionby adding, in a different reaction vessel
  15. stirringThe mixture was stirred at room temperature for 15 hours
  16. concentrationconcentrated
  17. custompartitioned by ethyl acetate (100 ml) and water (100 ml)
  18. extractionThe water layer was extracted with ethyl acetate (100 ml)
  19. dry with materialThe organic layer was dried over magnesium sulfate
  20. filtrationfiltered
  21. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-61613a00beaa47c799e5b8d8113b6c5a
Source dataset
uspto-grants-1995_02
Patent number
US05387684

Reaction notes

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