5-Amino-2-(trifluoromethyl)pyridine → 2-(2,6-dichlorophenyl)-1H-indole-6-carboxylic acid (6-trifluoromethylpyridin-3-yl)-amide

HRID 1514943ノート

反応式

HRID 1514943 の反応式
C[Al](C)C.[F:5][C:6]([F:15])([F:14])[C:7]1[N:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=1.[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=1[C:24]1[NH:25][C:26]2[C:31]([CH:32]=1)=[CH:30][CH:29]=[C:28]([C:33](OC)=[O:34])[CH:27]=2>C1(C)C=CC=CC=1>[F:15][C:6]([F:5])([F:14])[C:7]1[N:12]=[CH:11][C:10]([NH:13][C:33]([C:28]2[CH:27]=[C:26]3[C:31]([CH:32]=[C:24]([C:18]4[C:19]([Cl:23])=[CH:20][CH:21]=[CH:22][C:17]=4[Cl:16])[NH:25]3)=[CH:30][CH:29]=2)=[O:34])=[CH:9][CH:8]=1

参加物

5

反応物 3

HCID 27377445-Amino-2-(trifluoromethyl)pyridineHCID 16682925Trimethylaluminum2 回HCID 66965661methyl 2-(2,6-dichlorophenyl)-1H-indole-6-carboxylate

生成物 1

HCID 669652792-(2,6-dichlorophenyl)-1H-indole-6-carboxylic acid (6-trifluoromethylpyridin-3-yl)-amide

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

反応条件

温度
100 °C

実験手順

To 4 mL of ice-cold toluene was added 0.28 mL of 2 M trimethylaluminum in toluene then 6-trifluoromethyl-pyridin-3-ylamine (84 mg, 0.5 mmol) was added in one portion and the yellow solution was stirred for 30 min. To this was added a solution of methyl 2-(2,6-dichlorophenyl)-1H-indole-6-carboxylate (150 mg, 0.47 mmol) in toluene (5 mL) dropwise and the resulting solution was heated at 100° C. for 18 h. A second aliquot of trimethylaluminum was added and the mixture heated another 18 h, after which it was cooled to ambient temperature, quenched with 1N HCl. Water was added and the mixture was extracted with EtOAc (2×). The combined organic layers were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed using methylene chloride then 20% EtOAc/methylene chloride as eluent to give 2-(2,6-dichlorophenyl)-1H-indole-6-carboxylic acid (6-trifluoromethylpyridin-3-yl)-amide as a purple glass. MS (m/z) 449.9 (M+1); retention time=1.63 min (Method 10).

後処理

  1. temperaturethe mixture heated another 18 h
  2. temperatureafter which it was cooled to ambient temperature
  3. customquenched with 1N HCl
  4. additionWater was added
  5. extractionthe mixture was extracted with EtOAc (2×)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was chromatographed

出典と根拠

ORDレコード
ord-0afafe587539482c9f7963328fd5b1c0
出典データセット
uspto-grants-2012_07
特許番号
US08222248B2

反応ノート

読み込み中…