Tetrahydrofuran → HCID 9927823, compound

HRID 375851Notes

Reaction equation

HRID 375851 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]3[C:14]([C:15]([NH:16][CH2:17][CH:18]4[CH2:23][CH2:22][CH:21]([C:24](O)=[O:25])[CH2:20][CH2:19]4)=[C:6]2[CH:5]=[N:4]1)=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH3:2].C1COCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]3[C:14]([C:15]([NH:16][CH2:17][CH:18]4[CH2:23][CH2:22][CH:21]([CH2:24][OH:25])[CH2:20][CH2:19]4)=[C:6]2[CH:5]=[N:4]1)=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH3:2]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 21217722HCID 21217722, compoundHCID 21226445Aluminium lithium hydride2×

Product 1

HCID 9927823HCID 9927823, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of 1-ethyl-N-[(4-carboxycyclohexyl)methyl]-1H-pyrazolo[3,4-b]quinolin-4-amine (5.0 g), THF (100 ml) and lithium aluminum hydride (3.0 g) was refluxed overnight. Additional lithium aluminum hydride (1.0 g) was added and the mixture was heated at reflux for another hour. The reaction mixture was cooled, water (4 ml), then 10% NaOH (4 ml) and finally water (12 ml) were added and the mixture was heated to reflux and then filtered. The collected solids were heated at reflux in THF for 10 minutes, then filtered again. The filtrates were combined, dried over MgSO4 and then evaporated. The residue was purified by column chromatography on silica gel eluting with ethyl acetate and then was crystallized from hexanes/ethyl acetate. The product was dissolved in methanol, treated with methanesulfonic acid and then the methanol was evaporated. The residue was crystallized from 2-propanol and then recrystallized from 2-propanol to afford 1-ethyl-N-[(4-hydroxy methylcyclohexyl)methyl]-1H-pyrazolo[3,4-b]quinolin-4-amine.CH3SO3H, as a white solid, m.p. 188°-190° C.

Workup

  1. temperaturewas refluxed overnight
  2. temperaturethe mixture was heated
  3. temperatureat reflux for another hour
  4. temperatureThe reaction mixture was cooled
  5. temperaturethe mixture was heated
  6. temperatureto reflux
  7. filtrationfiltered
  8. temperatureThe collected solids were heated
  9. temperatureat reflux in THF for 10 minutes
  10. filtrationfiltered again
  11. dry with materialdried over MgSO4
  12. customevaporated
  13. customThe residue was purified by column chromatography on silica gel eluting with ethyl acetate
  14. customwas crystallized from hexanes/ethyl acetate
  15. dissolutionThe product was dissolved in methanol
  16. additiontreated with methanesulfonic acid
  17. customthe methanol was evaporated
  18. customThe residue was crystallized from 2-propanol
  19. customrecrystallized from 2-propanol

Sources & evidence

ORD record
ord-50b5962544cf4811b18253c499154328
Source dataset
uspto-grants-1996_01
Patent number
US05488055

Reaction notes

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