Sodium hydride → 7-chloro-6-fluoro-2-(isopropylamino)-1-phenyl-1,8-naphthyridin-4(1H)-one

HRID 1839373Notes

Reaction equation

[NH:1](/[C:8](/[NH:21][CH:22]([CH3:24])[CH3:23])=[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.[H-].[Na+]>CN(C=O)C.O>[Cl:19][C:15]1[N:14]=[C:13]2[C:12]([C:10](=[O:11])[CH:9]=[C:8]([NH:21][CH:22]([CH3:24])[CH3:23])[N:1]2[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:17][C:16]=1[F:18]

Participants

Conditions

Temperature: 85 °C

Procedure

(2Z)-3-Anilino-1-(2,6-dichloro-5-fluoro-3-pyridinyl)-3-(isopropylamino)-2-propen-1-one (40.0 mg, 0.109 mmol) was dissolved in 4 mL of DMF. NaH (8.70 mg, 0.217 mmol, 60% dispersion in oil) was added and the reaction was heated to 85° C. under argon for 2 h. The reaction mixture was cooled to room temperature and diluted with water and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue using Biotage silica gel chromatography eluting with 100% EtOAc to 95:5 EtOAc:MeOH provided 7-chloro-6-fluoro-2-(isopropylamino)-1-phenyl-1,8-naphthyridin-4(1H)-one (21 mg, 64%) as a white solid: LCMS RT: 2.57 min, MH+: 332.2.

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionthe aqueous layer was extracted with EtOAc
washThe combined organic extracts were washed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customPurification of the residue
washeluting with 100% EtOAc to 95:5 EtOAc

Sources & evidence

ORD record: ord-d482271daa2944fd90054e8141be4299
Source dataset: uspto-grants-2004_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06677352B1

Reaction notes

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