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

HRID 1867006노트

반응식

HRID 1867006 반응식
[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]

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 22050280Ethyl 5-(bromomethyl)pyrazine-2-carboxylateHCID 220504293-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methylpyridin-2(1H)-one

생성물 1

HCID 22050032Ethyl 5-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]methyl}pyrazine-2-carboxylate수율 78%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
55 °C

실험 절차

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).

후처리

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was triturated with water
  4. filtrationfiltered the solid
  5. washIt was washed with water
  6. customdried in vacuo

출처 및 근거

ORD 기록
ord-276708a0ab4e496a8e6b417b58cdfc19
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07629363B2

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