Sodium Iodide → HCID 10072481, compound

HRID 2103737Notes

Reaction equation

HRID 2103737 reaction equation
[CH2:1]([N:3]([CH2:26][CH3:27])[C:4](=[O:25])[C:5]1[CH:10]=[CH:9][C:8]([N:11]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[CH:7][CH:6]=1)[CH3:2].Cl.[CH3:29][N:30]([CH3:35])[CH2:31][CH2:32][CH2:33]Cl.[I-].[Na+].C(N(CC)CC)C>C(#N)C>[CH2:26]([N:3]([CH2:1][CH3:2])[C:4](=[O:25])[C:5]1[CH:6]=[CH:7][C:8]([N:11]([CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:12]2[CH2:17][CH2:16][N:15]([CH2:33][CH2:32][CH2:31][N:30]([CH3:35])[CH3:29])[CH2:14][CH2:13]2)=[CH:9][CH:10]=1)[CH3:27]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 943083-(Dimethylamino)propyl chloride hydrochlorideHCID 10406550HCID 10406550, compound2×

Product 1

HCID 10072481HCID 10072481, compoundYield 25.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of N,N-diethyl-4-[benzyl(piperidin-4-yl)amino]benzamide (Compound 8) (0.29 g, 0.793 mmole) in 25 mL of acetonitrile was added 3-(dimethylamino)propyl chloride hydrochloride (0.013 g, 0.793 mmol), sodium iodide (0.02 g, 0.119 mmol), and triethylamine (0.32 g, 3.18 mmol). The reaction mixture was refluxed for 20 hours under Argon and then was cooled and concentrated in vacuo. To the residue was added, aqueous sodium hydroxide (1 N) solution (30 mL), and the resulting solution was extracted three times with chloroform (25 mL). The organic extracts were combined, washed with sodium carbonate solution, dried (Na2SO4), and concentrated to provide a brown oil. This material was purified on a flash silica gel column (10% methanol-chloroform to 17.5% methanol-chloroform) to provide 0.09 g (25%) of N,N-diethyl-4-[benzyl(1-(3-dimethylaminopropyl)piperidin-4-yl)amino]benzamide as a pale rose glass. MS (ES), m/z 451 (MH+). 300 MHz 1H NMR (CDCl3) δ1.17 (t, J=7.0 Hz, 6H), 1.69-1.89 (m, 4H), 2.14 (br t, 2H), 2.18-2.38 (br m, 2H), 2.42 (s, 4H), 2.47 (t, J=7.1 Hz, 2H), 2.59 (t, J=6.9 Hz, 2H), 3.06 (br d, J=11.6 Hz, 2H), 3.30-3.49 (m, 4H), 3.72-3.90 (br m, 1H), 4.52 (s, 2H), 6.65 (d, J=8.7 Hz, 2H), 7.10-7.30 (m, 7H).

Workup

  1. temperatureThe reaction mixture was refluxed for 20 hours under Argon
  2. temperaturewas cooled
  3. concentrationconcentrated in vacuo
  4. additionTo the residue was added
  5. extractionaqueous sodium hydroxide (1 N) solution (30 mL), and the resulting solution was extracted three times with chloroform (25 mL)
  6. washwashed with sodium carbonate solution
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customto provide a brown oil
  10. customThis material was purified on a flash silica gel column (10% methanol-chloroform to 17.5% methanol-chloroform)

Sources & evidence

ORD record
ord-90c581a46bdd42518b9f61bb415642d2
Source dataset
uspto-grants-2009_08
Patent number
US07576105B2

Reaction notes

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