Diethylene Glycol Monomethyl Ether → 1-(4-Fluorophenyl)-6-(1-methylethyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile

HRID 2095805Notes

Reaction equation

CO/[CH:3]=[CH:4]/[C:5](=O)[CH:6]([CH3:8])[CH3:7].[C:10]([CH2:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)=[O:14])#[N:11].N12CCN(CC1)CC2.COCCOCCO>C(OCC)(=O)C>[F:22][C:19]1[CH:18]=[CH:17][C:16]([N:15]2[C:5]([CH:6]([CH3:8])[CH3:7])=[CH:4][CH:3]=[C:12]([C:10]#[N:11])[C:13]2=[O:14])=[CH:21][CH:20]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of (1E)-1-methoxy-4-methylpenta-1-en-3-one (508 mg, 3.96 mmol), 2-cyano-N-(4-fluorophenyl)acetamide (847 mg, 4.75 mmol), 1,4-diazabicyclo[2.2.2]octane (444 mg, 3.96 mmol) and 2-(2-methoxyethoxy)ethanol (10 mL) was stirred at 130° C. for 6 hr. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with 1N hydrochloric acid, water (×2) and saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→60/40) and silica gel column chromatography (NH silica gel, ethyl acetate/hexane=0/100→60/40) to give the title compound (604 mg, 59%) as a yellow solid.

Workup

temperatureAfter cooling to room temperature
washwashed with 1N hydrochloric acid, water (×2) and saturated brine
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
customThe solvent was evaporated under reduced pressure
customthe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→60/40) and silica gel column chromatography (NH silica gel, ethyl acetate/hexane=0/100→60/40)

Sources & evidence

ORD record: ord-8bb19a0d44b642d7a6cc67b29369b278
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445509B2

Reaction notes

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