Toluene → Methyl 3-amino-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate

HRID 2410739ノート

反応式

HRID 2410739 の反応式
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([O:20][CH3:21])=[O:19])=[CH:14][CH:13]=2)=[N:10][C:9](Br)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][C:29]=1[O:30][CH3:31].C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO>[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([O:20][CH3:21])=[O:19])=[CH:14][CH:13]=2)=[N:10][C:9]([C:26]2[CH:27]=[CH:28][C:29]([O:30][CH3:31])=[C:24]([F:23])[CH:25]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

参加物

7

反応物 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27821943-Fluoro-4-methoxyphenylboronic acidHCID 86663017Methyl 3-amino-6-bromo-2-(4-(methoxycarbonyl)phenyl)isonicotinate

生成物 1

HCID 66604696Methyl 3-amino-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate収率 80%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 887Methanol溶媒

反応条件

温度
125 °C

実験手順

A mixture of methyl 3-amino-6-bromo-2-(4-(methoxycarbonyl)phenyl)-isonicotinate (2.00 g, 5.48 mmol), 3-fluoro-4-methoxyphenylboronic acid (0.931 g, 5.48 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.316 g, 0.274 mmol) in a flask was flushed with nitrogen. Toluene (25 mL), MeOH (5 mL) and a 2 N aqueous solution of sodium carbonate (6.2 mL, 12.4 mmol) was added and the reaction was heated in a 125° C. oil bath for 2 hr. The reaction was partitioned between EtOAc and a saturated aqueous solution of sodium bicarbonate. The organic phase was separated and washed with a saturated aqueous solution of sodium bicarbonate and brine. It was dried with sodium sulfate and the solvents removed. Flash silica gel chromatography (elution with hexane containing 10% EtOAc) afforded methyl 3-amino-6-(3-fluoro-4-methoxyphenyl)-2-(4-(methoxycarbonyl)phenyl)isonicotinate (1.8 g). MS (ESI) m/z 411.2 (M+H). 1H NMR (CDCl3) δ ppm 8.18 (2H, d, J=8.24 Hz), 8.06 (1H, s), 7.81 (2H, d, J=8.24 Hz), 7.74 (1H, dd, J=12.97, 1.98 Hz), 7.68 (1H, d, J=8.85 Hz), 6.99 (1H, t, J=8.70 Hz), 5.98 (2H, br. s.), 3.97 (3H, s), 3.96 (3H, s), 3.92 (3H, s).

後処理

  1. customwas flushed with nitrogen
  2. customThe reaction was partitioned between EtOAc
  3. customThe organic phase was separated
  4. washwashed with a saturated aqueous solution of sodium bicarbonate and brine
  5. dry with materialIt was dried with sodium sulfate
  6. customthe solvents removed
  7. washFlash silica gel chromatography (elution with hexane containing 10% EtOAc)

出典と根拠

ORDレコード
ord-41cf9af2a6e74cc697255a49379ad130
出典データセット
uspto-grants-2014_08
特許番号
US08815840B2

反応ノート

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