Water → N-[6-Chloro-2-(1-piperazinyl)-5-quinolinyl]-cyclohexaneacetamide, Dihydrochloride

HRID 2217794Notes

Reaction equation

HRID 2217794 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:22])[C:8]=2[NH:12][C:13](=[O:21])[CH2:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)[N:3]=1.C(=O)([O-])[O-].[K+].[K+].[NH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.O>CN1CCCC1=O>[ClH:1].[ClH:1].[Cl:22][C:7]1[C:8]([NH:12][C:13](=[O:21])[CH2:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)[CH:11]=[CH:10]2

Participants

6

Reactant 4

HCID 962WaterHCID 4837PiperazineHCID 11430Potassium CarbonateHCID 86012996N-(2,6-Dichloro-5-quinolinyl)-cyclohexaneacetamide

Product 1

HCID 11374574N-[6-Chloro-2-(1-piperazinyl)-5-quinolinyl]-cyclohexaneacetamide, DihydrochlorideYield 69%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of N-(2,6-dichloro-5-quinolinyl)-cyclohexaneacetamide (Example 1 (a)) (170 mg) and potassium carbonate (350 mg) in N-methylpyrrolidinone (4 mL) was added piperazine (600 mg). The mixture was heated at 120° C. for 3 hours after which it was cooled and poured into water. The mixture was extracted with dichloromethane and the combined extracts evaporated to give a residue which was then partitioned between water and ethyl acetate. The organic layer was separated and the aqueous layer further extracted with ethyl acetate. The combined organic extracts were concentrated to give a residue which was purified by chromatography (SiO2, methanol:dichloromethane:ammonium hydroxide solution 19:80:1 as eluant) and the resultant product was converted to its hydrochloride salt by treatment with hydrochloric acid (4M in 1,4-dioxane). Recrystallisation (methanol/ethyl acetate) afforded the title compound as a solid (80 mg).

Workup

  1. temperaturewas cooled
  2. extractionThe mixture was extracted with dichloromethane
  3. customthe combined extracts evaporated
  4. customto give a residue which
  5. customwas then partitioned between water and ethyl acetate
  6. customThe organic layer was separated
  7. extractionthe aqueous layer further extracted with ethyl acetate
  8. concentrationThe combined organic extracts were concentrated
  9. customto give a residue which
  10. customwas purified by chromatography (SiO2, methanol:dichloromethane:ammonium hydroxide solution 19:80:1 as eluant)
  11. customRecrystallisation (methanol/ethyl acetate)

Sources & evidence

ORD record
ord-31fcc8ece102415c92ca42955c868518
Source dataset
uspto-grants-2008_08
Patent number
US07408065B2

Reaction notes

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