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

HRID 490177

반응식

HRID 490177 반응식
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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-84bdb20b9674483c9eeea99c715220a0
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07528134B2

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