Potassium Carbonate → 1-{3-[6-Chloro-2-(4-fluorophenyl)-1H-indol-1-yl]-1-oxopropyl}-4-(2-methoxyphenyl)piperazine

HRID 1016656Notes

Reaction equation

HRID 1016656 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[NH:8]2)=[CH:4][CH:3]=1.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[N:26]1[CH2:31][CH2:30][N:29]([C:32](=[O:35])[CH:33]=[CH2:34])[CH2:28][CH2:27]1.C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>CN(C)C=O.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:8]2[CH2:34][CH2:33][C:32]([N:29]2[CH2:30][CH2:31][N:26]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[O:19][CH3:18])[CH2:27][CH2:28]2)=[O:35])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 184070336-Chloro-2-(4-fluorophenyl)-1H-indoleHCID 184070531-[4-(2-methoxyphenyl)-1-piperazinyl]-2-Propen-1-one

Product 1

HCID 102781721-{3-[6-Chloro-2-(4-fluorophenyl)-1H-indol-1-yl]-1-oxopropyl}-4-(2-methoxyphenyl)piperazine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-chloro-2-(4-fluorophenyl)-1H-indole (Description 26, 348 mg, 1.4 mmol), 4-(2-methoxyphenyl)-1-(1-oxo-2-propenyl)piperazine (Description 25, 400 mg, 1.6 mmol) and potassium carbonate (1.5 g, 10.8 mmol) in dimethylformamide was stirred at 100° C. for 48 h. The mixture was cooled and aqueous ammonium chloride (saturated, 10 mL) and water (30 mL) were added. The mixture was extracted with ethyl acetate and the combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (50:50), to give the title compound. 1H NMR (360 MHz, CDCl3) δ 7.51 (1H, d, J 8.4 Hz), 7.45 (3H, m), 7.18 (2H, t, J 8.7 Hz), 7.11 (1H, dd, J 8.4, 1.8 Hz), 7.01 (1H, m), 6.93-6.81 (3H, m), 6.48 (1H, s), 4.51 (2H, t, J 7.7 Hz), 3.85 (3H, s), 3.72 (2H, t, J 5.0 Hz), 3.30 (2H, t, J 5.0 Hz), 2.93 (2H, t, J 5.0 Hz), 2.79 (2H, t, J 5.0 Hz), and 2.56 (2H, t, J 7.7 Hz). m/z (ES+) 492, 494 (M+1).

Workup

  1. temperatureThe mixture was cooled
  2. extractionThe mixture was extracted with ethyl acetate
  3. dry with materialthe combined organic fractions were dried (MgSO4)
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by flash column chromatography on silica gel
  6. washeluting with isohexane/EtOAc (50:50)

Sources & evidence

ORD record
ord-4cfca049d32b4996bcabdeb90434b5dc
Source dataset
uspto-grants-2002_11
Patent number
US06476045B2

Reaction notes

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