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

HRID 421889Notes

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, and saturated NaCl, dried over 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, and saturated NaCl
dry with materialdried over 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-6229ce4b27ef4e89829df75a7ac79ab2
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08101611B2

Reaction notes

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