Methanol → 3-Bromo-4-[(2,4-difluorobenzyl)oxy]-1-{[5-(hydroxymethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(1H)-one

HRID 1867007노트

반응식

HRID 1867007 반응식
[Br:1][C:2]1[C:3](=[O:31])[N:4]([CH2:19][C:20]2[N:21]=[CH:22][C:23]([C:26](OCC)=[O:27])=[N:24][CH:25]=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].C1COCC1.[BH4-].[Na+].CO>C(O)(C)(C)C.C(O)(=O)C>[Br:1][C:2]1[C:3](=[O:31])[N:4]([CH2:19][C:20]2[CH:25]=[N:24][C:23]([CH2:26][OH:27])=[CH:22][N:21]=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

7

반응물 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 22050032Ethyl 5-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]methyl}pyrazine-2-carboxylate

생성물 1

HCID 220506073-Bromo-4-[(2,4-difluorobenzyl)oxy]-1-{[5-(hydroxymethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(1H)-one수율 41.5%

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 6386tert-Butanol용매

실험 절차

To a suspension of ethyl 5-{[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]methyl}pyrazine-2-carboxylate (2.0 g, 0.004 mol) in t-butanol (15.0 mL and THF (5.0 mL) was added NaBH4 (0.18 g, 0.0047 mol) and the mixture was stirred at room temperature for 16 h under argon atmosphere. It was cooled, added MeOH (5.0 mL) and acetic acid (1.0 mL) and concentrated to dryness. The residue was triturated with water and filtered. It was washed with water, dried in vacuo and purified by flash chromatography (1% MeOH in EtOAc to afford the title compound (0.75 g, 41%) as a pale yellow powder: 1H NMR (CD3OD/400 MHz) δ 8.58 (d. 1H, J=1.6 Hz), 8.56 (d, 1H, J=1.6 Hz), 7.6 (m, 1H), 7.01 (m, 2H), 6.52 (s, 1H), 5.46 (s, 2H), 5.29 (s, 2H), 4.71 (s, 2H), and 2.54 (s, 3H); 19F NMR (CD3OD/400 MHz) δ −111.70 (m), and −116.06 (m); ES-HRMS m/z 452-0394 (M+H C19H17N3O3BrF2 requires 452.0416).

후처리

  1. temperatureIt was cooled
  2. concentrationconcentrated to dryness
  3. customThe residue was triturated with water
  4. filtrationfiltered
  5. washIt was washed with water
  6. customdried in vacuo
  7. custompurified by flash chromatography (1% MeOH in EtOAc

출처 및 근거

ORD 기록
ord-9cbcdab419ce418488b3f1626110d889
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07629363B2

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