Diethyl Ether → Methyl 3H-imidazo[4,5-c]pyridine-6-carboxylate

HRID 2377058Notes

Reaction equation

HRID 2377058 reaction equation
Cl.Cl.[N:3]1[C:11]2[CH2:10][C@@H:9]([C:12]([O:14][CH3:15])=[O:13])[NH:8][CH2:7][C:6]=2[NH:5][CH:4]=1.C(N(CC)CC)C.[Se](=O)=O.CCOCC>C(Cl)(Cl)(Cl)Cl>[N:3]1[C:11]2[CH:10]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[N:8]=[CH:7][C:6]=2[NH:5][CH:4]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 24007Selenium DioxideHCID 14403671Methyl (6S)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylate--hydrogen chloride (1/2)

Product 1

HCID 21892231Methyl 3H-imidazo[4,5-c]pyridine-6-carboxylateYield 47%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

Methyl (6S)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine-6-carboxylate dihydrochloride (156.5 g, 0.62 mol), triethylamine (445.0 g, 4.4 mol, 7.0 mol eqv.), selenium dioxide (158.2 g, 1.43 mol, 2.3 mol eqv.), and polyphosphatesilyl ether (PPSE) (15.0 g) were added to CCl4 (1.5 L). The mixture was refluxed for 6 h. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was suspended in methanol (1.5 L), and triethylamine was added to adjust to pH 8. The brown solid was filtered and washed well with methanol. This brown solid (117.0 g) was recrystallized from hot DMF (2 L, 140° C.). The solution was filtered hot to remove black side products. Upon cooling to room temperature, the desired product crystallized out as a yellow solid (51.3 g, 47% yield, 95% pure). 1H NMR (DMSO-d6): δ 13.20 (br s, 1H), 9.02 (s, 1H), 8.58 (s, 1H), 8.31 (s, 1H), 3.89 (s, 3H); LCMS: Rt=1.33 min, and M+1=178.1 u/e.

Workup

  1. temperatureThe mixture was refluxed for 6 h
  2. customthe solvent was removed under reduced pressure
  3. additiontriethylamine was added
  4. filtrationThe brown solid was filtered
  5. washwashed well with methanol
  6. customThis brown solid (117.0 g) was recrystallized from hot DMF (2 L, 140° C.)
  7. filtrationThe solution was filtered hot
  8. customto remove black side products
  9. temperatureUpon cooling to room temperature
  10. customthe desired product crystallized out as a yellow solid (51.3 g, 47% yield, 95% pure)

Sources & evidence

ORD record
ord-f0c442728b194e8c934f3768192cb013
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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