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

HRID 490177

反応式

HRID 490177 の反応式
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:18]=[C:19]([CH:23]=[CH:24][C:25]=1[F:26])[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]=[CH:24][C:25]([F:26])=[C:17]([F:16])[CH:18]=2)[CH2:12][CH:13]=1

参加物

6

反応物 4

HCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 5228323,4-DifluorobenzamideHCID 688728301',2',3',6'-Tetrahydro-2,4'-bipyridine hydrochloride

生成物 1

HCID 69002449N-(3',6'-dihydro-2,4'-bipyridin-1'(2'H)-ylmethyl)-3,4-difluorobenzamide収率 55%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

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), 3,4-diflurobenzamide (79 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 18 mg (55%) pure compound. 1H NMR (500 MHz, DMSO-d6) δ 2.58 (m, 2H), 2.79 (t, J=4 Hz, 2H), 3.32 (m, 2H), 4.28 (d, J=5 Hz, 2H), 6.71 (m, 1H), 7.22 (m, 1H), 7.55 (m, 2H), 7.83 (m, 2H), 7.95 (t, J=6 Hz, 1H), 8.52 (m, 1H) 8.95 (t, J=5 Hz, 1H); MS (ESI/APCI−) m/e 328 (M−H)+.

後処理

  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)

出典と根拠

ORDレコード
ord-84bdb20b9674483c9eeea99c715220a0
出典データセット
uspto-grants-2009_05
特許番号
US07528134B2

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