Ethylenediaminetetraacetic Acid → 2-anilino-6-fluoro-7-methyl-1-phenyl-1,8-naphthyridin-4(1H)-one

HRID 2215030Notes

Reaction equation

[NH:1]([C:8]1[N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]2[C:15]([C:16](=[O:18])[CH:17]=1)=[CH:14][C:13]([F:19])=[C:12](Cl)[N:11]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].C[Zn+].[CH2:30](N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O>C1COCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:1]([C:8]1[N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]2[C:15]([C:16](=[O:18])[CH:17]=1)=[CH:14][C:13]([F:19])=[C:12]([CH3:30])[N:11]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 75 °C

Procedure

To 2-anilino-7-chloro-6-fluoro-1-phenyl-1,8-naphthyridin-4(1H)-one (100 mg, 0.273 mmol) in THF (5 mL) was added Pd(PPh3)4 (13 mg, 0.001 mmol) and methyl zinc chloride (2M, 0.819 mL, 1.64 mmol) and the reaction was heated to 75° C. for 18 h. The reaction was then cooled to room temperature and poured into a solution of EDTA in water (2.5 g/20 mL) and extracted with Et2O. The organic layer was washed with brine and concentrated in vacuo. The residue was then taken up in MeOH and filtered. The filtrate was concentrated in vacuo to give 2-anilino-6-fluoro-7-methyl-1-phenyl-1,8-naphthyridin-4(1H)-one (83.0 mg, 89%): LCMS RT: 2.43 min, MH+: 346.4.

Workup

temperatureThe reaction was then cooled to room temperature
extractionextracted with Et2O
washThe organic layer was washed with brine
concentrationconcentrated in vacuo
filtrationfiltered
concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record: ord-024a8d5be9d14f8c9c415b84bd921929
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07109196B2

Reaction notes

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