Propionic Acid → Methyl 1-[4'-(2"-ethyl-5",7"-dimethylimidazo[4,5-b]pyridin-3-yl)methylphenyl]cyclopent-3-ene-1-carboxylate

HRID 1463530Notes

Reaction equation

HRID 1463530 reaction equation
[H-].[Na+].[CH2:3]([C:5]1[NH:15][C:8]2=[N:9][C:10]([CH3:14])=[CH:11][C:12]([CH3:13])=[C:7]2[N:6]=1)[CH3:4].NC1C=C(C)C=C(C)N=1.C(O)(=O)CC.Br[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2([C:43]([O:45][CH3:46])=[O:44])[CH2:42][CH:41]=[CH:40][CH2:39]2)=[CH:34][CH:33]=1>CN(C=O)C>[CH2:3]([C:5]1[N:15]([CH2:31][C:32]2[CH:33]=[CH:34][C:35]([C:38]3([C:43]([O:45][CH3:46])=[O:44])[CH2:42][CH:41]=[CH:40][CH2:39]3)=[CH:36][CH:37]=2)[C:8]2=[N:9][C:10]([CH3:14])=[CH:11][C:12]([CH3:13])=[C:7]2[N:6]=1)[CH3:4]

Participants

7

Reactant 5

HCID 1032Propionic AcidHCID 215072-Amino-4,6-dimethylpyridineHCID 24758Sodium hydrideHCID 19090689Methyl 1-(4'-bromomethylphenyl)cyclopent-3-ene-1-carboxylateHCID 178437439HCID 178437439, compound

Product 1

HCID 86747731Methyl 1-[4'-(2"-ethyl-5",7"-dimethylimidazo[4,5-b]pyridin-3-yl)methylphenyl]cyclopent-3-ene-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of sodium hydride (0.885 g, 22.1 mmol) in 50 ml of DMF at 0° C. was added a solution of 2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine (3.57 g, 20 mmol, prepared from 2-amino-4,6-dimethylpyridine by nitration, hydrogenolysis to the diamine and condensation with propionic acid and polyphosphoric acid, as described in EP 400974 A2) in 10 ml of DMF dropwise and the reaction mixture was warmed to room temperature. After 20 minutes the reaction was cooled to 0° C. and a solution of the product of Step 4, above, (5 g, 17 mmol) in 10 ml of DMF was added dropwise. The reaction was then allowed to warm to room temperature and stirred overnight then the DMF was removed in vacuo. The residue was taken up in water and extracted three times with ethyl acetate. The combined organics were washed with saturated sodium chloride solution, dried with MgSO4, filtered, evaporated and chromatographed on silica gel with a gradient elution from 5:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate to yield 5.8 g of the title compound as a pale yellow oil.

Workup

  1. temperatureAfter 20 minutes the reaction was cooled to 0° C.
  2. temperatureto warm to room temperature
  3. customthe DMF was removed in vacuo
  4. extractionextracted three times with ethyl acetate
  5. washThe combined organics were washed with saturated sodium chloride solution
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customchromatographed on silica gel with a gradient elution from 5:1 hexanes

Sources & evidence

ORD record
ord-cd6e458267034d4e816d6b358ac9cb27
Source dataset
uspto-grants-1994_04
Patent number
US05300668

Reaction notes

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