Hydrochloric Acid → 6-Amino-2-butoxy-9-(tetrahydrofuran-3-ylmethyl)-7,9-dihydro-8H-purin-8-one

HRID 1011179Notes

Reaction equation

HRID 1011179 reaction equation
[CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:21]C)[N:12]2[CH2:15][CH:16]2[CH2:20][CH2:19][O:18][CH2:17]2)=[C:8]([NH2:23])[N:7]=1)[CH2:2][CH2:3][CH3:4].Cl>CO.O1CCOCC1.[OH-].[Na+]>[NH2:23][C:8]1[N:7]=[C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])[N:14]=[C:13]2[C:9]=1[NH:10][C:11](=[O:21])[N:12]2[CH2:15][CH:16]1[CH2:20][CH2:19][O:18][CH2:17]1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 576996032-Butoxy-8-methoxy-9-(tetrahydrofuran-3-ylmethyl)-9H-purin-6-amine

Product 1

HCID 250251676-Amino-2-butoxy-9-(tetrahydrofuran-3-ylmethyl)-7,9-dihydro-8H-purin-8-oneYield 54.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

2-(Butyloxy)-8-(methoxy)-9-(tetrahydro-3-furanylmethyl)-9H-purin-6-amine (Isomer 2, 1.96 gm) was suspended in methanol (20 ml) and 4N HCl in dioxan (10 ml) added with stirring to give a clear solution. After 1.5 h, the solvents were evaporated to low volume and water added with stirring, followed by neutralisation with saturated sodium bicarbonate. The resulting off-white solid was filtered, washed with water and dried, yield 1.73 gm. Initial attempts to recrystallise from methanol or ethanol were unsuccessful. The recovered material was dissolved in glacial acetic acid (10 ml) with heating but precipitated immediately on addition of water (10 ml). Further addition of acetic acid (4 ml) and heating gave a clear solution, from which the product crystallised on allowing to cool. The solid was filtered, washed and dried, yield 1.06 gm (Crop 1). A second crop was obtained from the filtrate on standing, yield 460 mg, which was dissolved in sodium hydroxide and precipitated by the addition of acetic acid and then the recovered solid was heated in methanol (20 ml) with further additions of methanol (15 ml) to the boiling mixture to give a cloudy solution, which was allowed to cool. The resulting solid was filtered off, yield 257 mg. This was combined with the first batch of solid (Crop 1) and added portionwise to boiling methanol (130 ml) to give a slightly cloudy solution. On allowing to cool with stirring, a white solid crystallised out which was filtered off, washed with methanol and dried, to give the title compound yield 1.02 gm.

Workup

  1. customto give a clear solution
  2. customthe solvents were evaporated to low volume and water
  3. additionadded
  4. stirringwith stirring
  5. filtrationThe resulting off-white solid was filtered
  6. washwashed with water
  7. customdried
  8. customInitial attempts to recrystallise from methanol or ethanol
  9. dissolutionThe recovered material was dissolved in glacial acetic acid (10 ml)
  10. temperaturewith heating
  11. customprecipitated immediately on addition of water (10 ml)
  12. additionFurther addition of acetic acid (4 ml)
  13. temperatureheating
  14. customgave a clear solution
  15. customfrom which the product crystallised
  16. temperatureto cool
  17. filtrationThe solid was filtered
  18. washwashed
  19. customdried
  20. customA second crop was obtained from the filtrate
  21. customprecipitated by the addition of acetic acid
  22. temperaturethe recovered solid was heated in methanol (20 ml) with further additions of methanol (15 ml) to the boiling mixture
  23. customto give a cloudy solution, which
  24. temperatureto cool
  25. filtrationThe resulting solid was filtered off
  26. additionadded portionwise
  27. customto give a slightly cloudy solution
  28. temperatureto cool
  29. stirringwith stirring
  30. customa white solid crystallised out which
  31. filtrationwas filtered off
  32. washwashed with methanol
  33. customdried

Sources & evidence

ORD record
ord-01e16de3bfa94876b6bf57e850f96f4f
Source dataset
uspto-grants-2011_07
Patent number
US07977344B2

Reaction notes

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