Water → 6-bromo-3-(4-fluorobenzyl)-2H-pyrido[3,2-e][1,3]oxazin-4(3H)-one

HRID 2201542Notes

Reaction equation

ClCI.[Br:4][C:5]1[CH:6]=[N:7][C:8]([OH:22])=[C:9]([CH:21]=1)[C:10]([NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)=[O:11].[C:23]([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[Br:4][C:5]1[CH:6]=[N:7][C:8]2[O:22][CH2:23][N:12]([CH2:13][C:14]3[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=3)[C:10](=[O:11])[C:9]=2[CH:21]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Chloroiodomethane (897 mg, 5.1 mmol) was slowly added to a mixture of 5-bromo-N-(4-fluorobenzyl)-2-hydroxynicotinamide (1.5 g, 4.6 mmol) and Cs2CO3 (6.0 g, 18.4 mmol) in DMF (20 mL) at 100° C. The mixture was stirred at 100° C. for 2 h. Water was added and the mixture was extracted with EtOAc. After being concentrated, the residue was purified by column chromatography (PE:EtOAc=2:1) to give the product of 6-bromo-3-(4-fluorobenzyl)-2H-pyrido[3,2-e][1,3]oxazin-4(3H)-one (140 mg, yield: 9%). 1H-NMR (DMSO-d6, 400 MHz) δ 8.46 (d, J=2.4 Hz, 1H), 8.44 (d, J=2.4 Hz, 1H), 7.40 (dd, J=5.6, 8.8 Hz, 2H), 7.09 (t, J=8.8 Hz, 2H), 5.40 (s, 2H), 4.74 (s, 2H). MS (M+H)+: 337/339.

Workup

extractionthe mixture was extracted with EtOAc
concentrationAfter being concentrated
customthe residue was purified by column chromatography (PE:EtOAc=2:1)

Sources & evidence

ORD record: ord-fb1f458011c84a8a914292d3faf067a8
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09364482B2

Reaction notes

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