Cesium carbonate → 2-Methyl-5-[(3R)-3-methyl-1-piperazinyl]quinoline

HRID 1179607

Reaction equation

HRID 1179607 reaction equation
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][NH:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)S(O[C:66]1[CH:75]=[CH:74][CH:73]=[C:72]2[C:67]=1[CH:68]=[CH:69][C:70]([CH3:76])=[N:71]2)(=O)=O>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:76][C:70]1[CH:69]=[CH:68][C:67]2[C:72](=[CH:73][CH:74]=[CH:75][C:66]=2[N:6]2[CH2:5][CH2:4][NH:3][C@H:2]([CH3:1])[CH2:7]2)[N:71]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 73304342-Methylpiperazine, (R)-HCID 498518992-Methylquinolin-5-yl trifluoromethanesulfonate

Product 1

HCID 574443392-Methyl-5-[(3R)-3-methyl-1-piperazinyl]quinolineYield 58%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

(2R)-2-Methylpiperazine (0.550 g; 2 eq), caesium carbonate (1.78 g; 2 eq), palladium acetate (0.123 g; 0.2 eq) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.513 g; 0.3 eq) were added to a solution of 2-methyl-5-quinolinyl trifluoromethanesulfonate (D1) (0.8 g; 1 eq) in toluene (30 mL) under an inert atmosphere. The reaction mixture was stirred at reflux under nitrogen for 3 hours. The reaction cooled to room temperature, quenched using saturated aqueous ammonium chloride solution (15 mL) and extracted with ethyl acetate (3×20 mL). The organic layers were combined, dried over sodium sulfate and concentrated under reduced pressure. The crude was purified by flash chromatography on silica gel, eluting with dichloromethane-methanol (95:5) affording the title compound in 58% yield (0.383 g).

Workup

  1. temperatureat reflux under nitrogen for 3 hours
  2. customquenched
  3. extractionextracted with ethyl acetate (3×20 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude was purified by flash chromatography on silica gel
  7. washeluting with dichloromethane-methanol (95:5)

Sources & evidence

ORD record
ord-ff665965fea64949812a36f84c1c419f
Source dataset
uspto-grants-2007_10
Patent number
US07279481B2

Linked notes

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