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

HRID 2201538Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

Chloroiodomethane (800 mg, 4.6 mmol) was slowly added to a mixture of 2-bromo-N-(4-fluorobenzyl)-5-hydroxyisonicotinamide (750 mg, 2.3 mmol) and Cs2CO3 (3.0 g, 9.2 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=1:1) to give the product of 6-bromo-3-(4-fluorobenzyl)-2H-pyrido[4,3-e][1,3]oxazin-4(3H)-one (600 mg, yield: 80%). 1H-NMR (Methanol-d4, 400 MHz) δ 8.24 (s, 1H), 7.94 (s, 1H), 7.39 (dd, J=5.6, 8.0 Hz, 2H), 7.09 (t, J=8.8 Hz, 2H), 5.34 (s, 2H), 4.75 (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=1:1)

Sources & evidence

ORD record: ord-a332e401bcef4d6184465ff4c7954d44
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09364482B2

Reaction notes

Loading…