Tetrahydrofuran → HCID 9927823, compound

HRID 1586135Notes

Reaction equation

HRID 1586135 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) is refluxed overnight. Additional lithium aluminum hydride (1.0 g) is added, and the mixture is heated at reflux for another hour. The reaction mixture is cooled, water (4 ml), then 10% NaOH (4 ml) and finally water (12 ml) are added, and the mixture is heated to reflux and then filtered. The collected solids are heated at reflux in TBF for 10 minutes, then filtered again. The filtrates are combined, dried over MgSO4 and then evaporated. The residue is purified by column chromatography on silica gel eluting with ethyl acetate and then is crystallized from hexanes/ethyl acetate. The product is dissolved in methanol, treated with methanesulfonic acid and then the methanol is evaporated. The residue is crystallized from 2-propanol and then recrystallized from 2-propanol to afford 1-ethyl-N-[(4-hydroxymethylcyclohexyl)methyl]-1H-pyrazolo[3,4-b]quinolin-4-amine.CH3SO3H, as a white solid, m.p. 188°-190° C.

Workup

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

Sources & evidence

ORD record
ord-6ed1c929663246db8385794730942583
Source dataset
uspto-grants-1999_08
Patent number
US05942520

Reaction notes

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