3-Fluorophenol → 1-(3-Methoxy-phenoxy)-5H-benzo[c][1,8]naphthyridin-6-one

HRID 1029112Notes

Reaction equation

Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[C:4]1[CH:16]=[CH:15][CH:14]=[CH:13][C:5]=1[C:6](=[O:12])[NH:7]2.F[C:18]1[CH:19]=[C:20]([OH:24])[CH:21]=[CH:22][CH:23]=1.[C:25](=O)([O-])[O-:26].[K+].[K+]>CN(C=O)C.O>[CH3:25][O:26][C:18]1[CH:19]=[C:20]([CH:21]=[CH:22][CH:23]=1)[O:24][C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[C:4]1[CH:16]=[CH:15][CH:14]=[CH:13][C:5]=1[C:6](=[O:12])[NH:7]2

Participants

Conditions

Temperature: 100 °C

Procedure

1-Chloro-5H-benzo[c][1,8]naphthyridin-6-one (30 mg, 0.13 mmol), 3-fluorophenol (44 mg, 0.39 mmol), and potassium carbonate (90 mg, 0.65 mmol) were suspended in DMF (2 mL), and stirred overnight at 100° C. The reaction mixture was diluted with H2O, and extracted with EtOAc. The organic extracts were washed with brine, dried over MgSO4, filtered, and concentrated. The crude product was purified via Biotage eluting with a gradient of 25 to 75% EtOAc in hexanes to provide 126 (4 mg, 10% yield) as a solid. LC-MS (M+H=307, obsd.=307). 1H NMR (400 MHz, d6-DMSO): δ 12.17 (s, 1H), 9.00 (d, 1H), 8.43 (dd, 1H), 8.33 (d, 1H), 7.88 (dt, 1H), 7.71 (t, 1H), 7.58 (t, 1H), 7.36 (dt, 1H), 7.20 (m, 2H), 6.64 (d, 1H).

Workup

extractionextracted with EtOAc
washThe organic extracts were washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude product was purified via Biotage
washeluting with a gradient of 25 to 75% EtOAc in hexanes

Sources & evidence

ORD record: ord-dd300ed32b814afcaf438bcbd16d7005
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08735584B2

Reaction notes

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