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

HRID 490175

Reaction equation

HRID 490175 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.[Cl:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20]([NH2:22])=[O:21].[C:26](=O)([O-])[O-].[K+].[K+]>C(O)C>[Cl:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20]([NH:22][CH2:26][N:11]1[CH2:10][CH:9]=[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][N:2]=2)[CH2:13][CH2:12]1)=[O:21]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 692543-ChlorobenzamideHCID 688728301',2',3',6'-Tetrahydro-2,4'-bipyridine hydrochloride

Product 1

HCID 688764323-chloro-N-(3',6'-dihydro-2,4'-bipyridin-1'(2'H)-ylmethyl)benzamideYield 61%

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-chlorobenzamide (78 mg, 0.5 mmol, Lancaster), 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 20 mg (61%) pure compound. 1H NMR (500 MHz, DMSO-d6) δ 2.58 (m, 2H), 2.79 (t, J=4 Hz, 2H), 3.30 (m, 2H), 4.30 (d, J=5 Hz, 2H), 6.71 (m, 1H), 7.22 (m, 1H), 7.52 (m, 2H), 7.62 (d, J=6 Hz, 1H), 7.73 (t, J=6 Hz, 1H), 7.85 (d, J=6 Hz, 1H), 7.92 (s, 1H), 8.52 (m, 1H), 9.08 (t, J=5 Hz, 1H); MS (ESI/APCI−) m/e 326 (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-7c05a05324a24037bdf3321ea14c7281
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Linked notes

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