Hydroxylamine → 2-(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl-5-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)methyl-10,11-dihydro-5H-dibenzo[b,f]azepine

HRID 885431Notes

Reaction equation

HRID 885431 reaction equation
[C:1]([CH2:3][N:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[CH2:8][CH2:7][C:6]2[CH:15]=[C:16]([CH2:19][N:20]3[C:24]4=[N:25][C:26]([CH3:30])=[CH:27][C:28]([CH3:29])=[C:23]4[N:22]=[C:21]3[CH2:31][CH3:32])[CH:17]=[CH:18][C:5]1=2)#[N:2].NO.[N:35]1C=CC=CC=1.[C:41](Cl)(=[O:45])[O:42]CC.C(=O)([O-])O.[Na+].CC(C)([O-])C.[K+]>C(O)C.C(OCC)(=O)C>[CH2:31]([C:21]1[N:20]([CH2:19][C:16]2[CH:17]=[CH:18][C:5]3[N:4]([CH2:3][C:1]4[NH:35][C:41](=[O:45])[O:42][N:2]=4)[C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[CH2:8][CH2:7][C:6]=3[CH:15]=2)[C:24]2=[N:25][C:26]([CH3:30])=[CH:27][C:28]([CH3:29])=[C:23]2[N:22]=1)[CH3:32]

Participants

9

Reactant 6

HCID 787HydroxylamineHCID 1049PyridineHCID 10928Ethyl chloroformateHCID 516892Sodium BicarbonateHCID 18998700HCID 18998700, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 1363463472-(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl-5-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)methyl-10,11-dihydro-5H-dibenzo[b,f]azepineYield 84.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

[step 3] 5-Cyanomethyl-2-(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl-10,11-dihydro-5H-dibenzo[b,f]azepine (200 mg, 0.47 mmol) obtained in step 2 was dissolved in ethanol (4 mL), and the solution was added with hydroxylamine (50% aqueous solution, 0.15 mL, 2.37 mmol), followed by heating under reflux for 1 hr. The mixture was concentrated under reduced pressure. The obtained residue was dissolved in DMF (1 mL) and the solution was added with pyridine (46 μL, 0.57 mmol) and ethyl chlorocarbonate (54 μL, 0.57 mmol) at 0° C., followed by stirring at room temperature for 2 hr. Ethyl acetate and saturated aqueous sodium hydrogen carbonate solution were added thereto. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was dissolved in toluene (10 mL), and the solution was added with potassium tert-butoxide (51 mg, 0.45 mmol), followed by stirring at room temperature for 15 min. Ethyl acetate was added to the mixture, and the organic layer was washed with 5% aqueous citric acid solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (compound 1, 190 mg, 83%).

Workup

  1. temperatureby heating
  2. temperatureunder reflux for 1 hr
  3. concentrationThe mixture was concentrated under reduced pressure
  4. dissolutionThe obtained residue was dissolved in DMF (1 mL)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe obtained residue was dissolved in toluene (10 mL)
  9. stirringby stirring at room temperature for 15 min
  10. washthe organic layer was washed with 5% aqueous citric acid solution
  11. dry with materialdried over anhydrous magnesium sulfate
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7db0eceed31b41109063725535a87554
Source dataset
uspto-grants-2012_08
Patent number
US08242151B2

Reaction notes

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