Potassium Hydroxide → HCID 21912902, compound

HRID 1352544Notes

Reaction equation

HRID 1352544 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][N:11]1[C:19]2[C:18]([CH3:20])=[C:17]([CH3:21])[N:16]=[C:15](OC3C=CC=CC=3)[C:14]=2[N:13]=[C:12]1[CH2:29][CH2:30][CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[NH4+:36].[OH-].[K+]>>[CH2:1]([O:8][CH2:9][CH2:10][N:11]1[C:19]2[C:18]([CH3:20])=[C:17]([CH3:21])[N:16]=[C:15]([NH2:36])[C:14]=2[N:13]=[C:12]1[CH2:29][CH2:30][CH3:31])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 14797Potassium HydroxideHCID 517165Ammonium AcetateHCID 21912924HCID 21912924, compound

Product 1

HCID 21912902HCID 21912902, compoundYield 29.9%

Conditions

Temperature
156 °C

Procedure

1-[2-(Benzyloxy)ethyl]-6,7-dimethyl-4-phenoxy-2-propyl-1H-imidazo[4,5-c]pyridine (6.6 g, 15.8 mmol) and ammonium acetate (66 g) were combined in a dried glass pressure flask under nitrogen with stirring. The flask was sealed with a teflon screw cap and heated to 156° C. for 44 hours. The reaction was complete as determined by HPLC and LC/MS, and the resulting solution was cooled and basified to a pH of about 14 with 1 N potassium hydroxide. The basic solution was extracted with dichloromethane (5×), and the organic layers were combined, washed with 1 N potassium hydroxide (3×), water (1×) and brine (3×), dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was triturated with ethyl acetate/diethyl ether, and the resulting solids were filtered off and dried. NMR analysis of the solids indicated impurities. The solids were recrystallized from isopropyl alcohol and dried. Impurities were found in the resulting solids (3.2982 g), which were then recrystallized from ethyl acetate/hexane and again dried. The resulting solids (2.4076 g), still with impurities, were dissolved in ethanol, and the resulting solution was treated with 1 M hydrochloric acid in diethyl ether (10 mL). The resulting hydrochloride salt was filtered off, dissolved in water, and the aqueous solution was basified with 1N potassium hydroxide to a pH of about 14. The resulting aqueous mixture was extracted with dichloromethane (5×), and the combined organic layers were washed with water (3×) and brine (3×), dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting white solid was dried to provide 1.5999 g of 1-[2-(benzyloxy)ethyl]-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-4-amine, m.p. 99.5–100.0° C.

Workup

  1. customscrew cap
  2. temperaturethe resulting solution was cooled
  3. extractionThe basic solution was extracted with dichloromethane (5×)
  4. washwashed with 1 N potassium hydroxide (3×), water (1×) and brine (3×)
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was triturated with ethyl acetate/diethyl ether
  9. filtrationthe resulting solids were filtered off
  10. customdried
  11. customThe solids were recrystallized from isopropyl alcohol
  12. customdried
  13. customwere then recrystallized from ethyl acetate/hexane
  14. customagain dried
  15. dissolutionThe resulting solids (2.4076 g), still with impurities, were dissolved in ethanol
  16. additionthe resulting solution was treated with 1 M hydrochloric acid in diethyl ether (10 mL)
  17. filtrationThe resulting hydrochloride salt was filtered off
  18. dissolutiondissolved in water
  19. extractionThe resulting aqueous mixture was extracted with dichloromethane (5×)
  20. washthe combined organic layers were washed with water (3×) and brine (3×)
  21. dry with materialdried with magnesium sulfate
  22. filtrationfiltered
  23. concentrationconcentrated under reduced pressure
  24. customThe resulting white solid was dried

Sources & evidence

ORD record
ord-9f76ae0d1c7d4c1ca6221c2fa3d171b1
Source dataset
uspto-grants-2007_05
Patent number
US07220758B2

Reaction notes

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