Imidazole → 5-[2-(-1H-imidazol-1-yl)pyrid-5-yl]-1-azabicyclo[3.2.1]oct-3-ene

HRID 249749Notes

Reaction equation

HRID 249749 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].Br[C:9]1[CH:14]=[CH:13][C:12]([C:15]23[CH2:22][N:19]([CH2:20][CH2:21]2)[CH2:18][CH:17]=[CH:16]3)=[CH:11][N:10]=1>CN(C)C=O>[N:1]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]34[CH2:22][N:19]([CH2:20][CH2:21]3)[CH2:18][CH:17]=[CH:16]4)=[CH:11][N:10]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 102860575-(2-Bromopyrid-5-yl)-1-azabicyclo[3.2.1]oct-3-ene

Product 1

HCID 670500635-[2-(-1H-imidazol-1-yl)pyrid-5-yl]-1-azabicyclo[3.2.1]oct-3-eneYield 49.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

0.64 g (9.42 mmol) of imidazole dissolved in 3 ml of dimethylformamide is introduced into a 10 ml three-necked round-bottomed flask. 0.415 g (10.4 mmol) of sodium hydride as a 60% dispersion in oil is then added and the mixture is stirred at room temperature for 1 hour. The mixture is then added to a solution of 5-(2-bromopyrid-5-yl)-1-azabicyclo[3.2.1]oct-3-ene (WO 03/057 697) (0.5 g, 1.89 mmol) in dimethylformamide and the reaction medium is heated at 85° C. for 15 hours and then at 110° C. for 24 hours and the solvent is evaporated off under reduced pressure. The residue is taken up in 10 ml of chloroform and 10 ml of saturated aqueous sodium carbonate solution. The aqueous phase is extracted again with 10 ml of chloroform and the combined organic phases are washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified by chromatography on a column of silica gel, eluting with a mixture of chloroform, methanol and aqueous ammonia in 95/5/0.5 proportions. 0.235 g of 5-[2-(−1H-imidazol-1-yl)pyrid-5-yl]-1-azabicyclo[3.2.1]oct-3-ene is obtained and is dissolved in 3 ml of isopropyl alcohol to add 0.327 ml of a 5.7N solution of hydrobromic acid in acetic acid. The crystals formed are collected by filtration and dried under vacuum.

Workup

  1. additionis introduced into a 10 ml three-necked round-bottomed flask
  2. temperaturethe reaction medium is heated at 85° C. for 15 hours
  3. waitat 110° C. for 24 hours
  4. customthe solvent is evaporated off under reduced pressure
  5. extractionThe aqueous phase is extracted again with 10 ml of chloroform
  6. washthe combined organic phases are washed with saturated aqueous sodium chloride solution
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified by chromatography on a column of silica gel
  11. washeluting with a mixture of chloroform, methanol and aqueous ammonia in 95/5/0.5 proportions

Sources & evidence

ORD record
ord-a1e3d9654812429c94629f68b954f5be
Source dataset
uspto-grants-2011_01
Patent number
US07863290B2

Reaction notes

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