Formaldehyde → 4-fluoro-3-methyl-N-{[4-(2-pyridinyl)-1-piperazinyl]methyl}benzamide

HRID 490200Notes

Reaction equation

HRID 490200 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.C=O.[F:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]([NH2:22])=[O:21])=[CH:18][C:17]=1[CH3:25].[C:26](=O)([O-])[O-].[K+].[K+]>C(O)C>[F:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]([NH:22][CH2:26][N:10]2[CH2:9][CH2:8][N:7]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[CH2:12][CH2:11]2)=[O:21])=[CH:18][C:17]=1[CH3:25]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 944591-(2-Pyridyl)piperazineHCID 27745784-Fluoro-3-methylbenzamide

Product 1

HCID 688758194-fluoro-3-methyl-N-{[4-(2-pyridinyl)-1-piperazinyl]methyl}benzamideYield 76.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-pyridin-2-ylpiperazine (16 mg, 0.1 mmol, Aldrich), paraformaldehyde (30 mg, 1 mmol), 4-fluoro-3-methylbenzamide (77 mg, 0.5 mmol, Oakwood), and 42 mg of potassium carbonate (0.3 mmol) in 2 mL absolute ethyl alcohol was heated to reflux under nitrogen overnight. The mixture was cooled to room temperature, filtered, and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel (10% methanol:ethyl acetate) to give 25 mg (51%) pure compound. 1H NMR (500 MHz, DMSO-d6) δ 2.25 (s, 3H), 2.58 (t, J=4 Hz, 4H), 3.52 (t, J=4 Hz, 4H), 4.18 (d, J=5 Hz, 1H), 6.61 (t, J=5 Hz, 1H), 6.81 (d, J=6 Hz, 1H), 7.21 (t, J=6 Hz, 1H), 7.51 (t, J=5 Hz, 1H), 7.75 (t, J=5 Hz, 1H), 7.82 (d, J=6 Hz, 1H), 8.12 (d, J=5 Hz, 1H), 8.76 (t, J=5 Hz, 1H); MS (ESI/APCI−) m/e 327 (M−H)+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux under nitrogen overnight
  3. filtrationfiltered
  4. customthe solvent was removed under reduced pressure
  5. customThe residue was purified by flash column chromatography on silica gel (10% methanol:ethyl acetate)

Sources & evidence

ORD record
ord-fe1838a88b6d44fe8653c83445948d4e
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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