Diethyl Ether → 3-[1-[4-(4-Bromo-3-methoxyphenyl)-1-piperazinyl]ethyl]quinoline

HRID 1793438Notes

Reaction equation

HRID 1793438 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([CH:11]=O)[CH:2]=1.N1C2C=CC=C[C:16]=2N=N1.[Br:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[CH:25][C:24]=1[O:35][CH3:36].C[Mg]Br.C(OCC)C>C(O)C.C1(C)C=CC=CC=1.C(OCC)(=O)C>[Br:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:30][CH2:31][N:32]([CH:11]([C:3]3[CH:2]=[N:1][C:10]4[C:5]([CH:4]=3)=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH3:16])[CH2:33][CH2:34]2)=[CH:25][C:24]=1[O:35][CH3:36]

Participants

9

Reactant 5

HCID 3283Diethyl EtherHCID 836413-QuinolinecarboxaldehydeHCID 210710161-(4-Bromo-3-methoxyphenyl)piperazineHCID 178418385HCID 178418385, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 102960343-[1-[4-(4-Bromo-3-methoxyphenyl)-1-piperazinyl]ethyl]quinoline

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A solution containing 3-quinolinecarboxaldehyde (25 mg, 0.16 mmol, 1.0 equivalents), benzotriazole (19 mg, 0.16 mmol, 1.0 equivalents) and 1-(4-bromo-3-methoxy-phenyl)-piperazine (39 mg, 0.17 mmol, 1.1 equivalents) in ethanol (1 ml) and toluene (2 ml) was heated 20 minutes at 60° C. Solution was concentrated. Residue was coevaporated with toluene, then dissolved in THF and treated with 3.0 M solution of methyl magnesium bromide in diethyl ether (0.13 ml, 0.4 mmol, 2.5 equivalents). The reaction was stirred 18 hours at room temperature. The reaction was diluted with ethyl acetate and washed twice with 1N NaOH, brine, dried (MgSO4), filtered and concentrated. The residue was purified by preparative TLC to afford 3-{1-[4-(4-Bromo-3-methoxy-phenyl)-piperazin-1-yl]-ethyl}-quinoline (compound 3). Yield: 41 mg, 81%. Analysis H1 NMR (400 MHz, CDCl3): 8.96 (1H, s), 8.08 (2H, m), 7.82 (1H, d), 7.70 (1H, t), 7.56 (1H, t), 7.34 (1H, d), 6.45 (1H, m), 6.36 (1H, dd), 3.85 (3H, s), 3.68 (1H, q), 3.18 (4H, m), 2.73 (2H, m), 2.60 (2H, m), 1.54 (3H, d). MS (LC-MS): Calculated for C22H24BrN3O 426.11, found, 426.14 and 428.14, M+2.

Workup

  1. concentrationSolution was concentrated
  2. dissolutiondissolved in THF
  3. washwashed twice with 1N NaOH, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-1bb7eedc81724abd9e07461551a2da24
Source dataset
uspto-grants-2006_07
Patent number
US07081458B2

Reaction notes

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