Acetic Acid → 2-(4-Bromo-2-fluorophenylamino)-6-oxo-1,6-dihydropyridine-3-carboxylic acid

HRID 1817974Notes

Reaction equation

C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](=[O:11])[NH:7][C:6]=1[NH:12][C:13]1[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][C:14]=1[F:20])=[O:4].COC(=O)C1C=CC(OC)=NC=1NC1C=CC(Br)=CC=1F.C(O)(=O)C.Br>CCOC(C)=O>[Br:19][C:16]1[CH:17]=[CH:18][C:13]([NH:12][C:6]2[NH:7][C:8](=[O:11])[CH:9]=[CH:10][C:5]=2[C:3]([OH:4])=[O:2])=[C:14]([F:20])[CH:15]=1

Participants

Conditions

Temperature: 92.5 °C

Procedure

Preparation of 2-(4-bromo-2-fluorophenylamino)-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl ester: To 2-(4-bromo-2-fluorophenylamino)-6-methoxy-nicotinic acid methyl ester (1.00 g, 2.82 mmol) in a sealed flask was added glacial acetic acid (10 mL) and HBr (10 mL, 48 wt % in H2O). The reaction mixture was stirred at 90-95° C. for 2 hours and then cooled to room temperature. The reaction mixture was diluted with EtOAc and washed with H2O, saturated NaHCO3, saturated NaCl, dried (Na2SO4) and concentrated under reduced pressure. The crude product was triturated twice with dichloromethane/methanol and the resulting solid was collected and dried under vacuum to yield 0.756 g (79%) pure desired product as a white solid.

Workup

temperaturecooled to room temperature
washwashed with H2O, saturated NaHCO3, saturated NaCl
dry with materialdried (Na2SO4)
concentrationconcentrated under reduced pressure
customThe crude product was triturated twice with dichloromethane/methanol
customthe resulting solid was collected
customdried under vacuum

Sources & evidence

ORD record: ord-a9ee929d9ad44108a6695dca338264b0
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07598383B2

Reaction notes

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