Hydrochloric Acid → 1-(4-Fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

HRID 2095783Notes

Reaction equation

[C:1]([CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1)=[O:5])#[N:2].CO[CH:16]=[CH:17][C:18](=O)[CH3:19].N12CCN(CC1)CC2.CO/C=C/C(=O)C.Cl>COCCOCCO>[F:13][C:10]1[CH:9]=[CH:8][C:7]([N:6]2[C:18]([CH3:19])=[CH:17][CH:16]=[C:3]([C:1]#[N:2])[C:4]2=[O:5])=[CH:12][CH:11]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of 2-cyano-N-(4-fluorophenyl)acetamide (15 g, 84.2 mmol), 4-methoxybut-3-en-2-one (12.6 g, 125.9 mmol) and 1,4-diazabicyclo[2.2.2]octane (9.4 g, 84.2 mmol) in 2-(2-methoxyethoxy)ethanol (150 mL) was stirred with heating at 120° C. for 5 hr. (3E)-4-Methoxybut-3-en-2-one (4.2 g, 41.9 mmol) and 1,4-diazabicyclo[2,2,2]octane (4.7 g, 41.9 mmol) were further added to the reaction mixture, and the mixture was stirred with heating at 120° C. for 1 hr. 2N Hydrochloric acid was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered, and the solvent was evaporated under reduced pressure. The obtained solid was washed with ethyl acetate to give the title compound (6 g, 31%) as a pale-brown solid.

Workup

temperaturewith heating at 120° C. for 1 hr
extractionthe mixture was extracted with ethyl acetate
washThe organic layer was washed with saturated brine
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
customthe solvent was evaporated under reduced pressure
washThe obtained solid was washed with ethyl acetate

Sources & evidence

ORD record: ord-6abd68b8f551418a9767a5734fd8a080
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445509B2

Reaction notes

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