Formaldehyde → N-(3',6'-dihydro-2,4'-bipyridin-1'(2'H)-ylmethyl)-3,5-dimethylbenzamide

HRID 490180

Reaction equation

HRID 490180 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.[CH3:16][C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([CH3:26])[CH:25]=1)[C:20]([NH2:22])=[O:21].[C:27](=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]([CH2:27][NH:22][C:20](=[O:21])[C:19]2[CH:23]=[C:24]([CH3:26])[CH:25]=[C:17]([CH3:16])[CH:18]=2)[CH2:12][CH:13]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 3194853,5-DimethylbenzamideHCID 688728301',2',3',6'-Tetrahydro-2,4'-bipyridine hydrochloride

Product 1

HCID 68873067N-(3',6'-dihydro-2,4'-bipyridin-1'(2'H)-ylmethyl)-3,5-dimethylbenzamideYield 56%

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), 3,5-dimethylbenzamide (75 mg, 0.5 mmol), 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 18 mg (56%) pure compound. 1H NMR (500 MHz, DMSO-d6) δ2.33 (s, 6H), 2.56 (m, 2H), 2.78 (t, J=4 Hz, 2H), 3.28 (m, 2H), 4.18 (d, J=5 Hz, 2H), 6.71 (m, 1H), 7.18 (s, 1H), 7.22 (m, 1H), 7.50 (m, 3H), 7.75 (t, J=6 Hz, 1H), 8.52 (d, J=5 Hz, 1H), 8.62 (t, J=5 Hz, 1H), MS (ESI/APCI−) m/e 320 (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-beb57b0b56f84f2a97d28998edf34501
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Linked notes

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