Diethyl Ether → HCID 11219222, compound

HRID 352019Notes

Reaction equation

HRID 352019 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:7]2[CH:12]=[C:11]([CH3:13])[N:10]=[C:9](OC3C=CC=CC=3)[C:8]=2[N:21]=1)[CH3:2].C([O-])(=O)C.[NH4+:30].C(OCC)C>C(OCC)(=O)C>[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:7]2[CH:12]=[C:11]([CH3:13])[N:10]=[C:9]([NH2:30])[C:8]=2[N:21]=1)[CH3:2]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 517165Ammonium AcetateHCID 10404936HCID 10404936, compound

Product 1

HCID 11219222HCID 11219222, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A sealed glass tube containing 2-(ethoxymethyl)-1-(2-methylpropyl)-6-methyl-4-phenoxy-1H-imidazo[4,5-c]pyridine (2.51 g) from Part E and ammonium acetate (25.1 g) was heated to 150° C. After 36 hours, TLC monitoring indicated that the reaction was complete. The resulting reaction mixture was cooled and then dissolved in ethyl acetate. The ethyl acetate solution was washed with 25% aqueous sodium hydroxide. The resulting organic layer was dried with magnesium sulfate, and concentrated under reduced pressure to an orange oil. The oil was put through a column using 95/5 ethyl acetate/methanol, providing good separation. The oil recovered from the product fraction was dissolved in isopropyl alcohol, to which 1M HCl in diethyl ether was added. A white solid formed. More diethyl ether was added, and the white solid was filtered and dried under vacuum at 80° C. for 5 hours. The resulting solid was dissolved in water (50 ml), and the pH was adjusted to 11 using sodium carbonate. An oil separated and was extracted with dichloromethane. The resulting dichloromethane solution was dried with magnesium sulfate and concentrated under reduced pressure to a clear oil. The oil was triturated with methanol, and the resulting solid was dissolved in diethyl ether. The diethyl ether solution was subjected to high vacuum at room temperature to dry the product. The resulting partially solidified product was solidified by cooling with an isopropyl alcohol/dry ice bath to provide 2-(ethoxymethyl)-1-(2-methylpropyl)-6-methyl-1H-imidazo[4,5-c]pyridin-4-amine, m.p. 77.0-79.0° C.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas cooled
  3. washThe ethyl acetate solution was washed with 25% aqueous sodium hydroxide
  4. dry with materialThe resulting organic layer was dried with magnesium sulfate
  5. concentrationconcentrated under reduced pressure to an orange oil
  6. customproviding good
  7. customseparation
  8. customThe oil recovered from the product fraction
  9. dissolutionwas dissolved in isopropyl alcohol, to which 1M HCl in diethyl ether
  10. additionwas added
  11. customA white solid formed
  12. filtrationthe white solid was filtered
  13. customdried under vacuum at 80° C. for 5 hours
  14. dissolutionThe resulting solid was dissolved in water (50 ml)
  15. customAn oil separated
  16. extractionwas extracted with dichloromethane
  17. dry with materialThe resulting dichloromethane solution was dried with magnesium sulfate
  18. concentrationconcentrated under reduced pressure to a clear oil
  19. customThe oil was triturated with methanol
  20. dissolutionthe resulting solid was dissolved in diethyl ether
  21. customwas subjected to high vacuum at room temperature
  22. customto dry the product
  23. temperatureby cooling with an isopropyl alcohol/dry ice bath

Sources & evidence

ORD record
ord-3f9bc797d1274346bd1dde1aea74699a
Source dataset
uspto-grants-2004_06
Patent number
US06743920B2

Reaction notes

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