Water → N-(6-Methoxy-4-methyl-8-quinolinyl)2-methyl-4-(3-methylbutyl)-1-piperazinehexanamide

HRID 542832Notes

Reaction equation

HRID 542832 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([NH:9][C:10]1[CH:11]=[C:12]([O:21][CH3:22])[CH:13]=[C:14]2[C:19]=1[N:18]=[CH:17][CH:16]=[C:15]2[CH3:20])=[O:8].[CH3:23][CH:24]([CH3:34])[CH2:25][CH2:26][N:27]1[CH2:32][CH2:31][NH:30][CH:29]([CH3:33])[CH2:28]1.C(N(CC)CC)C.O>C1C=CC=CC=1>[CH3:22][O:21][C:12]1[CH:13]=[C:14]2[C:19](=[C:10]([NH:9][C:7](=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:30]3[CH2:31][CH2:32][N:27]([CH2:26][CH2:25][CH:24]([CH3:34])[CH3:23])[CH2:28][CH:29]3[CH3:33])[CH:11]=1)[N:18]=[CH:17][CH:16]=[C:15]2[CH3:20]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 6120236-Bromo-N-(6-methoxy-4-methyl-8-quinolinyl)hexanamideHCID 130775253-Methyl-1-(3-methylbutyl)piperazine

Product 1

HCID 20207179N-(6-Methoxy-4-methyl-8-quinolinyl)2-methyl-4-(3-methylbutyl)-1-piperazinehexanamideYield 44.3%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

A mixture of 6 g (0.0164 mole) of 6-bromo-N-(6-methoxy-4-methyl-8-quinolinyl)hexanamide, 3 g (0.017 mole) of 1-(3-methyl-butyl)-3-methylpiperazine and 3 ml of triethylamine in 100 ml of benzene was heated under reflux for 30 hr, allowed to cool and filtered to remove triethylamine hydrobromide. The filtrate was combined with 1 ml of triethylamine and heated under reflux for 28 hr. The cooled reaction mixture was combined with water and additional benzene. The benzene layer was separated, washed, dried and concentrated to dryness. The residue dissolved in ethyl acetate and chromatographed over 200 g of silica gel first with ethyl acetate, then with a 7% solution of methanol in ethyl acetate and finally with a 10% solution of methanol in ethyl acetate. Fractions containing product, Rf (15% methanol/ethyl acetate)=0.12, were combined and concentrated to afford 3.3 g (44%) of the desired product as an oil, which was used in the next step without further purification. The structure was confirmed by IR and NMR spectra.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 30 hr
  3. temperatureto cool
  4. filtrationfiltered
  5. customto remove triethylamine hydrobromide
  6. temperatureheated
  7. temperatureunder reflux for 28 hr
  8. customThe cooled reaction mixture
  9. customThe benzene layer was separated
  10. washwashed
  11. customdried
  12. concentrationconcentrated to dryness
  13. dissolutionThe residue dissolved in ethyl acetate
  14. customchromatographed over 200 g of silica gel first with ethyl acetate
  15. additionFractions containing product, Rf (15% methanol/ethyl acetate)=0.12
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-98b64feaeea54b819989125b907cf19b
Source dataset
uspto-grants-1987_04
Patent number
US04659708

Reaction notes

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