Potassium Carbonate → 3-[3-[4-(2-pyridinyl)-1-piperazinyl]propyl]-5-nitro-1H-indole

HRID 441077Notes

Reaction equation

HRID 441077 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH2:13][CH2:14][CH2:15]Br)([O-:3])=[O:2].[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:23]1[CH2:24][CH2:25][N:26]([CH2:15][CH2:14][CH2:13][C:7]2[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[NH:9][CH:8]=2)[CH2:27][CH2:28]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 944591-(2-Pyridyl)piperazineHCID 199620433-(3-Bromopropyl)-5-nitro-1H-indole

Product 1

HCID 199620423-[3-[4-(2-pyridinyl)-1-piperazinyl]propyl]-5-nitro-1H-indoleYield 36%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-[3-bromopropyl]-5-nitro-1H-indole (4) (1.4 g, 4.2 mmol), 1-(2-pyridinyl)-piperazine, (1) (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, 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 purified by flash silica gel chromatography (5% methanol in dichloromethane) to give 3-[3-[4-(2-pyridinyl)-1-piperazinyl]propyl]-5-nitro-1H-indole, (0.6 g, 36%) as a yellow solid: 1H NMR (DMSO-d6, 300 MHz) δ 8.52 (d, J=2.24 Hz, 1H), 8.80 (dd, J=1.8, 4.8 Hz, 1H), 7.95 (dd, J= 2.25, 9.0 Hz, 1H), 7.52-7.49 (m, 2H), 7.41 (s, 1H), 6.79 (d, J=8.6 Hz, 1H), 6.60 (t, J=6.6 Hz, 1H), 3.46 (t, J=4.7 Hz, 4H), 2.78 (t, J=7.4 Hz, 2H), 2.42 (t, J=5.0 Hz, 4H), 2.34 (t, J=6.9 HZ, 4H), 1.82 (dt, J=7.4, 6.9 Hz, 2H); IR(KBr) 3182, 1520, 1330 cm-1 ; MS (m/e) 365 (M+). Anal. Calcd for C20H23N5O2 : C, 65.73, H, 6.34, N 19.16; found C, 65.35, H, 6.26, N, 18.87.

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 purified by flash silica gel chromatography (5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-155dbd0c169d493d9fc1bffca38a83a5
Source dataset
uspto-grants-1996_05
Patent number
US05521188

Reaction notes

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