Piperazine → 2-tert-Butyl-4-cyclobutyl-6-(piperazin-1-yl)pyrimidine

HRID 219691Notes

Reaction equation

HRID 219691 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:7]([C:11]1[N:16]=[C:15](Cl)[CH:14]=[C:13]([CH:18]2[CH2:21][CH2:20][CH2:19]2)[N:12]=1)([CH3:10])([CH3:9])[CH3:8]>C(O)C>[C:7]([C:11]1[N:16]=[C:15]([N:1]2[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]2)[CH:14]=[C:13]([CH:18]2[CH2:21][CH2:20][CH2:19]2)[N:12]=1)([CH3:10])([CH3:8])[CH3:9]

Participants

4

Reactant 2

HCID 4837PiperazineHCID 860953852-Tert-butyl-4-chloro-6-cyclobutyl-pyrimidine

Product 1

HCID 666733902-tert-Butyl-4-cyclobutyl-6-(piperazin-1-yl)pyrimidineYield 65.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

24.8 g of piperazine (287.9 mmol) were dissolved in 350 ml of ethanol and heated to reflux. 24.9 g of 2-tert-butyl-4-chloro-6-cyclobutyl-pyrimidine (48.06 mmol), dissolved in 50 ml of ethanol, were added dropwise to the solution. The solution was refluxed for further 3 h, cooled to room temperature and then extracted with water and ethyl acetate. The organic layer was washed with 5% citric acid (aq.), and the aqueous layer was adjusted to alkaline pH with 2 N NaOH. The alkaline aqueous layer was reextracted with ethyl acetate, and the organic phase was dried over magnesium sulfate, filtered and concentrated to dryness to yield 8.6 g (65.2%) of the title compound.

Workup

  1. temperatureheated to reflux
  2. additionwere added dropwise to the solution
  3. temperatureThe solution was refluxed for further 3 h
  4. extractionextracted with water and ethyl acetate
  5. washThe organic layer was washed with 5% citric acid (aq.)
  6. dry with materialthe organic phase was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-f60fd41591214d999566f293ab790b42
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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