3,3-Dianilino-1-(2,6-dichloro-5-fluoro-3-pyridinyl)-2-propen-1-one → 2-anilino-7-chloro-6-fluoro-1-phenyl-1,8-naphthyridin-4(1H)-one

HRID 1839364Notes

Reaction equation

[NH:1]([C:8]([NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[CH:9][C:10]([C:12]1[C:13](Cl)=[N:14][C:15]([Cl:19])=[C:16]([F:18])[CH:17]=1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+]>O1CCOCC1>[NH:1]([C:8]1[N:21]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:13]2[C:12]([C:10](=[O:11])[CH:9]=1)=[CH:17][C:16]([F:18])=[C:15]([Cl:19])[N:14]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 3,3-dianilino-1-(2,6-dichloro-5-fluoro-3-pyridinyl)-2-propen-1-one (2.3 g, 5.7 mmol) and t-BuOK (1.28 g, 11.4 mmol) in dioxane (80 mL) was stirred at 80° C. overnight. The reaction was cooled, concentrated in vacuo, diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo. Silica gel flash chromatography of the residue provided 2-anilino-7-chloro-6-fluoro-1-phenyl-1,8-naphthyridin-4(1H)-one (1.0 g, 50as a light yellow solid: LCMS RT: 2.60 min, MH+: 366.8. This transformation can be accomplished by using the combination of other aprotic solvents such as DMF, and THF with other bases such as NaH.

Workup

temperatureThe reaction was cooled
concentrationconcentrated in vacuo
additiondiluted with water
extractionextracted with EtOAc
washThe combined organic extracts were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-259de5bc5e9746a3b28790785b14c6b0
Source dataset: uspto-grants-2004_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06677352B1

Reaction notes

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