Formaldehyde → N-(3',6'-dihydro-2,4'-bipyridin-1'(2'H)-ylmethyl)cyclohexanecarboxamide

HRID 490176

Reaction equation

HRID 490176 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH2:9][CH2:10][NH:11][CH2:12][CH:13]=1.C=O.[CH:16]1([C:22]([NH2:24])=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.[C:25](=O)([O-])[O-].[K+].[K+]>C(O)C>[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH2:9][CH2:10][N:11]([CH2:25][NH:24][C:22]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:23])[CH2:12][CH:13]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 14283CyclohexanecarboxamideHCID 688728301',2',3',6'-Tetrahydro-2,4'-bipyridine hydrochloride

Product 1

HCID 68872384N-(3',6'-dihydro-2,4'-bipyridin-1'(2'H)-ylmethyl)cyclohexanecarboxamideYield 64%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl hydrochloride (20 mg, 0.10 mmol, Saari, W. S.; et al. J. Med. Chem. 1984, 27, 1182), paraformaldehyde (30 mg, 1 mmol), cyclohexanecarboxylic acid amide (64 mg, 0.5 mmol, Aldrich), and 42 mg of potassium carbonate (0.3 mmol) in 2.5 mL absolute ethyl alcohol was heated to reflux under nitrogen overnight. The mixture was cooled to room temperature, filtered, and the solvent was removed. The residue was purified by flash column chromatography on silica gel (10% methanol:ethyl acetate) to give 19 mg (64%) pure compound. 1H NMR (500 MHz, DMSO-d6) δ 1.19 (m, 4H), 1.26 (m, 2H), 1.61 (m, 1H), 1.68 (m, 3H), 2.18 (m, 1H), 2.55 (m, 2H), 2.68 (m, 2H), 3.18 (m, 2H), 4.02 (d, J=5 Hz, 2H), 6.68 (m, 1H), 7.22 (m, 1H), 7.52 (d, J=6 Hz, 1H), 7.73 (t, J=6 Hz, 1H), 8.02 (t, J=5 Hz, 1H), 8.52 (m, 1H); MS (ESI/APCI−) m/e 298 (M−H)+.

Workup

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

Sources & evidence

ORD record
ord-3c91708860f2402382132a49cb1bde89
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Linked notes

Loading…