Piperazine → 6-Methoxy-5-piperazin-1-yl-quinoline

HRID 992085Notes

Reaction equation

HRID 992085 reaction equation
Br[C:2]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[NH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].O.CC1C=CC=CC=1C>[CH3:13][O:12][C:11]1[C:2]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[C:3]2[C:8](=[CH:9][CH:10]=1)[N:7]=[CH:6][CH:5]=[CH:4]2

Participants

8

Reactant 4

HCID 4837PiperazineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 184141285-Bromo-6-methoxyquinolineHCID 23676156Sodium t-butoxide

Product 1

HCID 184140826-Methoxy-5-piperazin-1-yl-quinolineYield 6%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 962WaterSolventHCID 7237O-XyleneSolvent

Conditions

Temperature
120 °C

Procedure

To an oven-dried 100 mL flask under N2 atmosphere was added 5-bromo-6-methoxyquinoline (3 g, 12.6 mmol), piperazine (6.5 g. 75.6 mmol), Pd(dba)2 (570 mg, 5 mol %), P(t-Bu)3 (0.628 mL, 5 mol %) and sodium t-butoxide (1.82 g, 18.9 mmol). 50 mL dry o-xylene was added and the reaction mixture stirred and heated at 120° C. for 3 hours, then at room temperature overnight. The reaction mixture was poured into H2O (100 mL) and extracted into EtOAc (3×100 mL). The organic fractions were combined, dried over Na2SO4, concentrated and purified by column chromatography (10% MeOH/CH2Cl2+NH4OH) affording 170 mg (6%) of 6-methoxy-5-piperazin-1-yl-quinoline. This material was used without further purification (combined with another batch) in the next step. (Ref: Tet Lett. 1998, 39, p. 617-620).

Workup

  1. customat room temperature
  2. customovernight
  3. extractionextracted into EtOAc (3×100 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. custompurified by column chromatography (10% MeOH/CH2Cl2+NH4OH)

Sources & evidence

ORD record
ord-5e6142dc14104c9fac879d751dc3b168
Source dataset
uspto-grants-2002_10
Patent number
US06465482B2

Reaction notes

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