Acetic Acid → Ethyl 5-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]methyl}pyrazine-2-carboxylate

HRID 1867006Notes

Reaction equation

[Br:1][C:2]1[C:3](=[O:19])[NH:4][C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].Br[CH2:21][C:22]1[N:23]=[CH:24][C:25]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[N:26][CH:27]=1.[H-].[Na+].C(O)(=O)C>C1COCC1>[Br:1][C:2]1[C:3](=[O:19])[N:4]([CH2:21][C:22]2[N:23]=[CH:24][C:25]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[N:26][CH:27]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

Conditions

Temperature: 55 °C

Procedure

To a mixture of 3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one (6.0 g, 0.018 mol) and ethyl 5-(bromomethyl)pyrazine-2-carboxylate (4.9 g, 0.02 mol) in THF (50.0 mL) was added NaH (0.5 g) and heated at 55° C. under argon atmosphere for 3 h. The reaction mixture was cooled added acetic acid (1.2 ml) and concentrated under reduced pressure. The residue was triturated with water and filtered the solid. It was washed with water, followed by ethanol and dried in vacuo to afford the title compound (3.0 g, 78%)as alight brown powder: 1H NMR (CD3OD/400 MHz) δ9.10 (d. 1H, J=1.2 Hz), 8.77 (d, 1H, J=1.2 Hz), 7.61 (m, 1H), 7.01 (m 2H), 6.54 (s, 1H), 5.54 (s, 2H), 5.30 (s, 2H), 4.43 (q, 2H, J=6.8 Hz), 2.52 (s, 3H), and 1.39 (t, 3H, J=6.8 Hz); 19F NMR (CD3OD/400 MHz) δ−111.64 (m), and −116.04 (m); ES-HRMS m/z 494.0482 (M+H C21H19N3O4BrF2 requires 494.0522).

Workup

temperatureThe reaction mixture was cooled
concentrationconcentrated under reduced pressure
customThe residue was triturated with water
filtrationfiltered the solid
washIt was washed with water
customdried in vacuo

Sources & evidence

ORD record: ord-276708a0ab4e496a8e6b417b58cdfc19
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07629363B2

Reaction notes

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