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

HRID 490201Notes

Reaction equation

HRID 490201 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.[F:16][C:17]1[CH:25]=[CH:24][C:20]([C:21]([NH2:23])=[O:22])=[CH:19][C:18]=1[CH3:26].[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:23][C:21](=[O:22])[C:20]2[CH:24]=[CH:25][C:17]([F:16])=[C:18]([CH3:26])[CH:19]=2)[CH2:12][CH:13]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 27745784-Fluoro-3-methylbenzamideHCID 688728301',2',3',6'-Tetrahydro-2,4'-bipyridine hydrochloride

Product 1

HCID 68871973N-(3',6'-dihydro-2,4'-bipyridin-1'(2'H)-ylmethyl)-4-fluoro-3-methylbenzamideYield 28%

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), 4-fluoro-3-methylbenzamide (77 mg, 0.5 mmol, Oakwood), 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 under reduced pressure. The residue was purified by flash column chromatography on silica gel (10% methanol:ethyl acetate) to give 9 mg (28%) pure compound. 1H NMR (500 MHz, DMSO-d6) δ 2.28 (s, 3H), 2.56 (m, 2H), 2.76 (m, 2H), 3.30 (m, 2H), 4.26 (d, J=5 Hz, 2H), 6.70 (m, 1H), 7.20 (m, 2H), 7.50 (d, J=6 Hz, 1H), 7.75 (m, 2H), 7.85 (d, J=6 Hz, 1H), 8.51 (m, 1H) 8.77 (t, J=5 Hz, 1 H); MS (ESI/APCI−) m/e 324 (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-b43df00d240e4ada8fa5810bfd03aa90
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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