Dimethylformamide → 4-(6-fluoro-3-pyridinyl)methoxy-1-{4-[2-(1-piperidinyl)ethoxy]phenyl}-1H-pyridin-2-one

HRID 15040Notes

Reaction equation

HRID 15040 reaction equation
CN(C=O)C.[OH:6][C:7]1[CH:12]=[CH:11][N:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:15][CH:14]=2)[C:9](=[O:28])[CH:8]=1.[H-].[Na+].[F:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38]OS(C)(=O)=O)=[CH:34][N:33]=1>C(OCC)(=O)C>[F:31][C:32]1[N:33]=[CH:34][C:35]([CH2:38][O:6][C:7]2[CH:12]=[CH:11][N:10]([C:13]3[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][N:22]4[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]4)=[CH:17][CH:18]=3)[C:9](=[O:28])[CH:8]=2)=[CH:36][CH:37]=1

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 684300184-hydroxy-1-{4-[2-(1-piperidinyl)ethoxy]phenyl}-1H-pyridin-2-oneHCID 86614892(6-Fluoropyridin-3-yl)methyl methanesulphonate

Product 1

HCID 589649424-(6-fluoro-3-pyridinyl)methoxy-1-{4-[2-(1-piperidinyl)ethoxy]phenyl}-1H-pyridin-2-oneYield 45.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Into a DMF solution (0.8 mL) of 4-hydroxy-1-{4-[2-(1-piperidinyl)ethoxy]phenyl}-1H-pyridin-2-one (20 mg, 0.065 mmol), NaH (60% oiliness, 3 mg, 0.078 mmol) was added and stinred at room temeture for 20 minutes, followed by addition of DMF solution (0.2 mL) of 2-fluoro-5-methanesulfonyloxymethylpyridine (20 mg, 0.097 mmol), stirring at the same temperature for 2.5 hours and further an overnight stirring at 80° C. Ethyl acetate was added to the reaction liquid, which was then washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine and dried over anhydrous sodium sulfate. Concentrating the solvent under reduced pressure, the resulting residue was purified on silica gel column chromatography (C-300; methanol:chloroform=1:10) to provide the title compound (12.5 mg, 45%).

Workup

  1. stirringstirring at 80° C
  2. washwas then washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationConcentrating the solvent under reduced pressure
  5. customthe resulting residue was purified on silica gel column chromatography (C-300; methanol:chloroform=1:10)

Sources & evidence

ORD record
ord-cbf3b2d9f2324b2095cde49cb14f378d
Source dataset
uspto-grants-2010_06
Patent number
US07732456B2

Reaction notes

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