Water → 3-(4,5,6,7-Tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)propylamine

HRID 349567Notes

Reaction equation

HRID 349567 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[N:7]1[N:11]2[CH2:12][CH2:13][CH2:14][NH:15][C:10]2=[C:9]([CH2:16][CH2:17][C:18]([NH2:20])=O)[CH:8]=1.[F-].[K+].O>O1CCCC1>[N:7]1[N:11]2[CH2:12][CH2:13][CH2:14][NH:15][C:10]2=[C:9]([CH2:16][CH2:17][CH2:18][NH2:20])[CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 522689Potassium FluorideHCID 21226445Aluminium lithium hydrideHCID 1357327583-(4,5,6,7-Tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)propionamide

Product 1

HCID 1357327643-(4,5,6,7-Tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)propylamineYield 75.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of lithium aluminum hydride (7.6 g) in tetrahydrofuran (300 ml) was added 3-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)propionamide (10 g) at room temperature. The mixture was stirred under reflux for 2 days. After cooling on an ice bath, potassium fluoride (34 g) and water (10 ml) were added to the reaction mixture. The insoluble materials were removed by filtration. To the filtrate were added 10% aqueous sodium carbonate solution (100 ml) and di-tert-butyl dicarbonate (20.0 g). The mixture was stirred at room temperature for 1 hour. After evaporation of the solvent in vacuo, the residue was dissolved in chloroform. The solution was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. To the oily residue were added methanol (100 ml) and 4 mol/l hydrogen chloride solution in dioxane (50 ml), and the mixture was stirred under reflux for 30 minutes. The reaction mixture was concentrated in vacuo to give crude 3-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl)propylamine (7.0 g) as an oil. This product was used in the next step without further purification.

Workup

  1. temperatureunder reflux for 2 days
  2. temperatureAfter cooling on an ice bath
  3. customThe insoluble materials were removed by filtration
  4. additionTo the filtrate were added 10% aqueous sodium carbonate solution (100 ml) and di-tert-butyl dicarbonate (20.0 g)
  5. stirringThe mixture was stirred at room temperature for 1 hour
  6. customAfter evaporation of the solvent in vacuo
  7. dissolutionthe residue was dissolved in chloroform
  8. washThe solution was washed with water
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. additionTo the oily residue were added methanol (100 ml) and 4 mol/l hydrogen chloride solution in dioxane (50 ml)
  13. stirringthe mixture was stirred
  14. temperatureunder reflux for 30 minutes
  15. concentrationThe reaction mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-d4804818712c485d8d0e775a3296fb5c
Source dataset
uspto-grants-2007_02
Patent number
US07179801B2

Reaction notes

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