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

HRID 490171Notes

Reaction equation

HRID 490171 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([NH2:8])=[O:7].C([O-])([O-])=O.[K+].[K+].[CH2:18]=O.Cl.[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]1[CH2:28][CH2:29][NH:30][CH2:31][CH:32]=1>C(O)C>[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]1[CH2:28][CH2:29][N:30]([CH2:18][NH:8][C:6](=[O:7])[C:5]2[CH:9]=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:31][CH:32]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 984873-MethoxybenzamideHCID 688728301',2',3',6'-Tetrahydro-2,4'-bipyridine hydrochloride

Product 1

HCID 68874678N-(3',6'-dihydro-2,4'-bipyridin-1'(2'H)-ylmethyl)-3-methoxybenzamideYield 49%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

3-Methoxybenzamide (1.13 g, 7.5 mmol), K2CO3 (345 mg, 2.5 mmol), paraformaldehyde (0.5 g, 16 mmol), and 1′,2′,3′,6′-tetrahydro-2,4′-bipyridine hydrochloride (393 mg, 2 mmol) were combined in ethanol (25 ml) and refluxed for 18 hours. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure. The residue was partitioned between ethyl acetate (80 mL) and water (80 mL). The organic layer was washed with brine (2×50 mL), dried over MgSO4, filtered, and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (elution with ethyl acetate:ethanol, 9.0:1.0) to provide the title compound (180 mg, 49% yield). 1H NMR (300 MHz, DMSO-d6) δ 2.58 (m, 2H), 2.76 (t, 2H, J=6 Hz), 3.29 (m, 2H), 3.80 (s, 3H), 4.27 (d, 2H, J=6 Hz), 6.70 (m, 1H), 7.09 (m, 1H), 7.22 (m, 1H), 7.42 (m, 4H), 7.72 (m, 1H), 8.51 (m, 1H), 8.83 (t, 1H, J=6 Hz); MS (DCI/NH3) m/e 324 (M+H)+.

Workup

  1. temperaturerefluxed for 18 hours
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was partitioned between ethyl acetate (80 mL) and water (80 mL)
  4. washThe organic layer was washed with brine (2×50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel (elution with ethyl acetate:ethanol, 9.0:1.0)

Sources & evidence

ORD record
ord-430c647e9998449c99bced5335b09bf6
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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