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

HRID 490186

Reaction equation

HRID 490186 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.[CH:15]1([C:21]([NH2:23])=[O:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.[C:24](=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]([CH2:24][NH:23][C:21]([CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)=[O:22])[CH2:11][CH2:12]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 14283CyclohexanecarboxamideHCID 944591-(2-Pyridyl)piperazine

Product 1

HCID 10470197N-{[4-(2-pyridinyl)-1-piperazinyl]methyl}cyclohexanecarboxamideYield 99.2%

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), cyclohexanecarboxylic acid amide (64 mg, 0.5 mmol, Aldrich), 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 (66%) pure compound. 1H NMR (500 MHz, DMSO-d6) δ 1.05-1.40 (m, 5H), 1.59-1.68 (m, 5H), 2.15 (m, 1H), 2.48 (m, 4H), 3.45 (t, J=4 Hz, 4H), 3.95 (d, J=5 Hz, 1H), 6.62 (t, J=6 Hz, 1H), 6.81 (d, J=6 Hz, 1H), 7.53 (t, J=6 Hz, 1H), 8.01 (t, J=5 Hz, 1H), 8.10 (d, J=5 Hz, 1H); MS (ESI/APCI−) m/e 301 (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-7ff2b7dec02241dd9e4288b00af3a76a
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Linked notes

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