4,6-Dichloropyrimidine → 4-Chloro-6-(piperazin-1-yl)pyrimidine

HRID 68556Notes

Reaction equation

HRID 68556 reaction equation
[N:1]1([C:7](OC(C)(C)C)=O)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.[Cl:23][C:24]1[CH:29]=C(Cl)[N:27]=[CH:26][N:25]=1>ClCCl>[Cl:23][C:24]1[CH:29]=[C:7]([N:1]2[CH2:2][CH2:3][NH:4][CH2:5][CH2:6]2)[N:27]=[CH:26][N:25]=1

Participants

5

Reactant 3

HCID 709434,6-DichloropyrimidineHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 160922664-Chloro-6-(piperazin-1-yl)pyrimidineYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

13.3 g tert-butyl 1-piperazinecarboxylate and 11.2 mL DIPEA were added to 10 g 4, 6 dichloro pyrimidine in 1000 mL dichlormethane was stirred over the weekend at RT. The solvent was removed. The residue was dissolved in 200 mL dichlormethane and 200 mL trifluoro acetic acid was added. The reaction was stirred at RT. The solvent was removed. The residue was dissolved in methanol and passed through HCO3 containing resin. The solvent was removed and the residue was purified by chromatographie on silica (dcyclohexane: ethylacetate 0-40%) to yield 13.07 g of the desired product.

Workup

  1. customThe solvent was removed
  2. dissolutionThe residue was dissolved in 200 mL dichlormethane
  3. addition200 mL trifluoro acetic acid was added
  4. stirringThe reaction was stirred at RT
  5. customThe solvent was removed
  6. dissolutionThe residue was dissolved in methanol
  7. customThe solvent was removed
  8. customthe residue was purified by chromatographie on silica (dcyclohexane: ethylacetate 0-40%)

Sources & evidence

ORD record
ord-fcc9c374f65c4aafa624fd70903d5b38
Source dataset
uspto-grants-2014_09
Patent number
US08822464B2

Reaction notes

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