Potassium Carbonate → 3-[3-[4-(3-methoxy-4-pyridinyl)-1-piperazinyl]propyl]-5-nitro-1H-indole

HRID 53147Notes

Reaction equation

HRID 53147 reaction equation
I[CH2:2][CH2:3][CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([N+:14]([O-:16])=[O:15])[CH:12]=2)[NH:7][CH:6]=1.[CH3:17][O:18][C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:24]=1[N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[CH3:17][O:18][C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:24]=1[N:25]1[CH2:26][CH2:27][N:28]([CH2:2][CH2:3][CH2:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([N+:14]([O-:16])=[O:15])[CH:12]=3)[NH:7][CH:6]=2)[CH2:29][CH2:30]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 152883081-(3-Methoxypyridin-4-yl)piperazineHCID 199620503-[3-iodopropyl]-5-nitro-1H-indole

Product 1

HCID 199620483-[3-[4-(3-methoxy-4-pyridinyl)-1-piperazinyl]propyl]-5-nitro-1H-indoleYield 36.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-[3-iodopropyl]-5-nitro-1H-indole (1.4 g, 4.2 mmol), 1-(3-methoxy-4-pyridinyl)-piperazine (0.98 g, 5.09 mmol) and K2CO3 (1.4 g, 10.2 mmol) in 30 mL of acetonitrile was heated to reflux for 4 h. The reaction mixture was cooled and stirred for 12 h. The solvent was removed and the residue dissolved in ethyl acetate and water. The aqueous layer was separated and extracted with ethyl acetate. The organic extracts were dried (MgSO4) and concentrated, and the gummy residue was purified by flash silica gel chromatography (5% methanol in dichloromethane as eluant) to give 3-[3-[4-(3-methoxy-4-pyridinyl)-1-piperazinyl]propyl]-5-nitro-1H-indole, (0.6 g, 36%) as a yellow solid: IR (KBr) 3600, 2400, 1600, 1520, 1330, 1250, 815 cm-1 ; 1H NMR (DMSO-d6, 300 MHz) δ8.52 (d, J=2.2 Hz, 1H), 8.10 (s, 1H), 8.02 (d, J=5.3 Hz, 1H), 7.96 (dd, J=2.3, 9.0 Hz, 1H), 7.48. (d, J=9.0 Hz, 1H), 7.42 (s, 1H), 6.81 (d, J=5.4 Hz, 1H), 3.84 (s, 3H), 3.21 (br s, 4H), 3.07 (dd, J=6.4, 14.7 Hz, 2H), 2.79 (t, J=14.7 Hz, 2H), 2.66 (br s, 4H), 1.97 (m, 2H); MS (m/e) 395 (M+).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 4 h
  3. temperatureThe reaction mixture was cooled
  4. customThe solvent was removed
  5. dissolutionthe residue dissolved in ethyl acetate
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate
  8. dry with materialThe organic extracts were dried (MgSO4)
  9. concentrationconcentrated
  10. customthe gummy residue was purified by flash silica gel chromatography (5% methanol in dichloromethane as eluant)

Sources & evidence

ORD record
ord-3c9f988252eb45aeb5b3f15da20f1b37
Source dataset
uspto-grants-1997_04
Patent number
US05618816

Reaction notes

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