Quipazine → Methyl 5-(4-quinolin-2-ylpiperazin-1-yl)hexanoate

HRID 1714786Notes

Reaction equation

HRID 1714786 reaction equation
O=[C:2]([CH3:10])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH3:9])=[O:7].[N:11]1([C:17]2[CH:26]=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=2)[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1>C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>[N:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:25]=[CH:26][C:17]=1[N:11]1[CH2:16][CH2:15][N:14]([CH:2]([CH3:10])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH3:9])=[O:7])[CH2:13][CH2:12]1

Participants

5

Reactant 2

HCID 5011QuipazineHCID 84129Methyl 5-oxohexanoate

Product 1

HCID 23155655Methyl 5-(4-quinolin-2-ylpiperazin-1-yl)hexanoateYield 45%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 1.10 g of methyl 5-oxo-hexanoate as synthesized in above step 7-14-A, 1.36 g of 2-piperazin-1-ylquinoline, 20 mg of p-toluenesulfonic acid and 50 ml of toluene was heated under reflux for 16 hours, and the formed water was azeotropically removed. The solvent was concentrated under reduced pressure. The residue was dissolved in 50 ml of tetrahydrofuran, and the solution was stirred at room temperature for an hour while hydrogen chloride gas was introduced thereinto. Then 380 mg of sodium cyanotrihydroborate as dissolved in 10 ml of methanol was added, followed by 2 hours' stirring. To the solution, 0.1N aqueous potassium hydroxide was added, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and the solvent was concentrated under reduced pressure. The residue was purified on silica gel column chromatography (ethyl acetate:n-hexane=1:1) to provide 977 mg (45%) of methyl 5-(4-quinoline-2-ylpiperazin-1-yl)hexanoate.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 16 hours
  3. customthe formed water was azeotropically removed
  4. concentrationThe solvent was concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in 50 ml of tetrahydrofuran
  6. additionwas introduced
  7. dissolutionThen 380 mg of sodium cyanotrihydroborate as dissolved in 10 ml of methanol
  8. additionwas added
  9. stirring' stirring
  10. additionTo the solution, 0.1N aqueous potassium hydroxide was added
  11. extractionfollowed by extraction with ethyl acetate
  12. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  13. concentrationthe solvent was concentrated under reduced pressure
  14. customThe residue was purified on silica gel column chromatography (ethyl acetate:n-hexane=1:1)

Sources & evidence

ORD record
ord-75ca939b49b3410ca68bd06e33f2c948
Source dataset
uspto-grants-2010_09
Patent number
US07799775B2

Reaction notes

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