Formic Acid → 2-cyclopropyl-3-(2'-cyanobiphenyl-4-yl)-methyl-7-methyl-3H-imidazo[4,5-b]pyridine

HRID 744981Notes

Reaction equation

HRID 744981 reaction equation
[CH:1]1([C:4]2[N:14]([CH2:15][C:16]3C=[CH:20][C:19](C4C=CC=CC=4C#N)=[CH:18][CH:17]=3)[C:7]3=[N:8][CH:9]=[C:10](Br)[C:11]([CH3:12])=[C:6]3[N:5]=2)[CH2:3][CH2:2]1.[CH:30](O)=O.C([N:35]([CH2:38][CH3:39])CC)C.[C:40]1(C)[CH:45]=[CH:44]C=[CH:42][CH:41]=1>[Pd]>[CH:1]1([C:4]2[N:14]([C:15]3[CH:16]=[CH:17][C:18]([C:44]4[CH:45]=[CH:40][CH:41]=[CH:42][C:39]=4[C:38]#[N:35])=[CH:19][CH:20]=3)[C:7]3=[N:8][C:9]([CH3:30])=[CH:10][C:11]([CH3:12])=[C:6]3[N:5]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 284Formic AcidHCID 1140TolueneHCID 8471TriethylamineHCID 15837816HCID 15837816, compound

Product 1

HCID 677136852-cyclopropyl-3-(2'-cyanobiphenyl-4-yl)-methyl-7-methyl-3H-imidazo[4,5-b]pyridineYield 78%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

Toluene (30 ml) was added to 2.0 g (4.5 mmol) of 2-cyclopropyl-3-(2'-cyanobiphenyl-4-yl)methyl-6-bromo-7-methyl-3H-imidazo[4,5-b]pyridine, 1.24 g (27.0 mmol) of formic acid, 4.55 g (45.0 mmol) of triethylamine and 10% Pd-C (100 mg), followed by heating under reflux for 6 hours. After the reaction liquid was brought to room temperature and filtered to remove the catalyst, vacuum concentration was effected. Chloroform (50 ml) and water (50 ml) were added to the residue and the obtained mixture was caused liquid-liquid separation. The aqueous phase was further extracted with chloroform (30 ml) twice. The organic phases were combined, dried over anhydrous magnesium sulfate and subjected to vacuum concentration. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to give 1.28 g of 2-cyclopropyl-3-(2'-cyanobiphenyl-4-yl)-methyl-7-methyl-3H-imidazo[4,5-b]pyridine (yield 78%).

Workup

  1. temperatureby heating
  2. temperatureunder reflux for 6 hours
  3. customAfter the reaction liquid
  4. customwas brought to room temperature
  5. filtrationfiltered
  6. customto remove
  7. concentrationthe catalyst, vacuum concentration
  8. additionChloroform (50 ml) and water (50 ml) were added to the residue
  9. customliquid-liquid separation
  10. extractionThe aqueous phase was further extracted with chloroform (30 ml) twice
  11. dry with materialdried over anhydrous magnesium sulfate
  12. concentrationsubjected to vacuum concentration
  13. customThe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-7930694e61ae4546867eee77a25c96ef
Source dataset
uspto-grants-1996_09
Patent number
US05559236

Reaction notes

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