Ammonium Acetate → HCID 21913012, compound

HRID 1352558Notes

Reaction equation

HRID 1352558 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:23][CH2:24][O:25][CH2:26][CH2:27][CH2:28][C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)[C:7]2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=[C:9](OC3C=CC=CC=3)[C:8]=2[N:22]=1)[CH3:2].C([O-])(=O)C.[NH4+:39]>C(OCC)(=O)C>[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:23][CH2:24][O:25][CH2:26][CH2:27][CH2:28][C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)[C:7]2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=[C:9]([NH2:39])[C:8]=2[N:22]=1)[CH3:2]

Participants

4

Reactant 2

HCID 517165Ammonium AcetateHCID 21913908HCID 21913908, compound

Product 1

HCID 21913012HCID 21913012, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Under a nitrogen atmosphere, 2-(ethoxymethyl)-6,7-dimethyl-4-phenoxy-1-[2-(3-pyridin-3-ylpropoxy)ethyl]-1H-imidazo[4,5-c]pyridine (4.6 g) from Part A and ammonium acetate (46 g) were heated in a sealed tube to 150° C. After 65 hours, NMR analysis indicated that the reaction was complete. The reaction mixture was cooled to ambient temperature, dissolved in ethyl acetate, and washed 3 times with 1N potassium hydroxide and once with water. The organic layers were dried with magnesium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in 10% hydrochloric acid and washed 3 times with dichloromethane (DCM). Potassium hydroxide was added to the aqueous layer to bring the pH to 14, and this was subsequently washed 4 times with DCM. The combined organic layers were washed twice with water, twice with brine, dried with magnesium sulfate, and concentrated under reduced pressure. The oil was purified by column chromatography over silica using 98/2 DCM/methanol as the eluant. The oil was then triturated with ethyl acetate/hexane and the resulting solid was recrystallized from ethyl acetate/hexane to yield 2-(ethoxymethyl)-6,7-dimethyl-1-[2-(3-pyridin-3-ylpropoxy)ethyl]-1H-imidazo[4,5-c]pyridin-4-amine as a white solid, m.p. 78.0–78.5° C.

Workup

  1. washwashed 3 times with 1N potassium hydroxide
  2. dry with materialThe organic layers were dried with magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe resulting residue was dissolved in 10% hydrochloric acid
  5. washwashed 3 times with dichloromethane (DCM)
  6. additionPotassium hydroxide was added to the aqueous layer
  7. washthis was subsequently washed 4 times with DCM
  8. washThe combined organic layers were washed twice with water, twice with brine
  9. dry with materialdried with magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe oil was purified by column chromatography over silica using 98/2 DCM/methanol as the eluant
  12. customThe oil was then triturated with ethyl acetate/hexane
  13. customthe resulting solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-62f88c9e97ab4abd99dca86d17f6c431
Source dataset
uspto-grants-2007_05
Patent number
US07220758B2

Reaction notes

Loading…