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

HRID 490184

Reaction equation

HRID 490184 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]([F:27])([F:26])[C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20]([NH2:22])=[O:21].[C:28](=O)([O-])[O-].[K+].[K+]>C(O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:8][CH2:9][N:10]([CH2:28][NH:22][C:20](=[O:21])[C:19]2[CH:23]=[CH:24][CH:25]=[C:17]([C:16]([F:26])([F:27])[F:15])[CH:18]=2)[CH2:11][CH2:12]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 74535m-(Trifluoromethyl)benzamideHCID 944591-(2-Pyridyl)piperazine

Product 1

HCID 10044299N-{[4-(2-pyridinyl)-1-piperazinyl]methyl}-3-(trifluoromethyl)benzamideYield 82.3%

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), 3-trifluoromethylbenzamide (95 mg, 0.5 mmol), 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 30 mg (55%) pure compound. 1H NMR (500 MHz, DMSO-d6) δ 2.60 (t, J=4 Hz, 4H), 3.52 (t, J=4 Hz, 4H), 4.22 (d, J=5 hz, 1H), 6.62 (t, J=5 Hz, 1H), 6.81 (d, J=6 Hz, 1H), 7.51 (t, J=6 Hz, 1H), 7.75 (d, J=6 Hz, 1H), 7.92 (d, J=6 Hz, 1H), 8.12 (d, J=5 Hz, 1H), 8.10 (m, 2H), 9.05 (t, J=5 Hz, 1H); MS (ESI/APCI−) m/e 363 (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-e4091f0d9a1c479a8d99e6eed22dd9aa
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Linked notes

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