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

HRID 1867007ノート

反応式

HRID 1867007 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 6386tert-Butanol溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-9cbcdab419ce418488b3f1626110d889
出典データセット
uspto-grants-2009_12
特許番号
US07629363B2

反応ノート

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