Ammonium Acetate → 2,6,7-trimethyl-1-[2-(3-pyridin-3-ylpropoxy)ethyl]-1H-imidazo[4,5-c]pyridin-4-amine

HRID 1008016Notes

Reaction equation

HRID 1008016 reaction equation
[CH3:1][C:2]1[N:3]([CH2:20][CH2:21][O:22][CH2:23][CH2:24][CH2:25][C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[C:4]2[C:9]([CH3:10])=[C:8]([CH3:11])[N:7]=[C:6](OC3C=CC=CC=3)[C:5]=2[N:19]=1.C([O-])(=O)C.[NH4+:36]>C(OCC)(=O)C>[CH3:1][C:2]1[N:3]([CH2:20][CH2:21][O:22][CH2:23][CH2:24][CH2:25][C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[C:4]2[C:9]([CH3:10])=[C:8]([CH3:11])[N:7]=[C:6]([NH2:36])[C:5]=2[N:19]=1

Participants

4

Reactant 2

HCID 517165Ammonium AcetateHCID 219131992,6,7-trimethyl-4-phenoxy-1-[2-(3-pyridin-3-ylpropoxy)ethyl]-1H-imidazo[4,5-c]pyridine

Product 1

HCID 100885762,6,7-trimethyl-1-[2-(3-pyridin-3-ylpropoxy)ethyl]-1H-imidazo[4,5-c]pyridin-4-amine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Under a nitrogen atmosphere, 2,6,7-trimethyl-4-phenoxy-1-[2-(3-pyridin-3-ylpropoxy)ethyl]-1H-imidazo[4,5-c]pyridine (4 g) from Part D and ammonium acetate (40 g) were heated in a sealed tube to 150° C. After 46.5 hours, NMR analysis indicated that only 7% of the starting material remained. The reaction mixture was cooled to ambient temperature, diluted with ethyl acetate, and washed 3 times with IN potassium hydroxide and once with water. The organic layers were dried with magnesium sulfate and concentrated under reduced pressure. The resulting oil was triturated with 90/10 diethyl ether/toluene and the filtered solids were dried under vacuum at 45° C. The pale yellow solid was dissolved in 10% hydrochloric acid and extracted 3 times with dichloromethane (DCM). Potassium hydroxide was added to the aqueous layer to bring the pH to 14, and this was subsequently washed 3 times with DCM. The combined organic layers were washed once with water, 3 times with brine, dried with magnesium sulfate, and concentrated under reduced pressure. The oil was purified by column chromatography over silica using 97/3 DCM/methanol as the eluant. The oil was then triturated with diethyl ether/toluene and the resulting solid was recrystallized from ethyl acetate/hexane to yield 2,6,7-trimethyl-1-[2-(3-pyridin-3-ylpropoxy)ethyl]-1H-imidazo[4,5-c]pyridin-4-amine, m.p. 108.6-109.5° C.

Workup

  1. washwashed 3 times with IN potassium hydroxide
  2. dry with materialThe organic layers were dried with magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting oil was triturated with 90/10 diethyl ether/toluene
  5. customthe filtered solids were dried under vacuum at 45° C
  6. dissolutionThe pale yellow solid was dissolved in 10% hydrochloric acid
  7. extractionextracted 3 times with dichloromethane (DCM)
  8. additionPotassium hydroxide was added to the aqueous layer
  9. washthis was subsequently washed 3 times with DCM
  10. washThe combined organic layers were washed once with water, 3 times with brine
  11. dry with materialdried with magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe oil was purified by column chromatography over silica using 97/3 DCM/methanol as the eluant
  14. customThe oil was then triturated with diethyl ether/toluene
  15. customthe resulting solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-c13ad31cb30a43bf84ae29edaa030ec8
Source dataset
uspto-grants-2004_09
Patent number
US06797718B2

Reaction notes

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