5-bromo-1-(4-fluorophenyl)-1H-indazole → 1-Allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carbonitrile

HRID 244442ノート

反応式

HRID 244442 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[N:6]=[CH:5]2.[Li]CCCC.[CH2:23]([N:26]1[CH:30]=[C:29]([C:31](=[O:36])[C:32]([F:35])([F:34])[F:33])[CH:28]=[C:27]1[C:37]#[N:38])[CH:24]=[CH2:25]>C1COCC1>[CH2:23]([N:26]1[CH:30]=[C:29]([C:31]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[N:6]=[CH:5]3)([OH:36])[C:32]([F:35])([F:33])[F:34])[CH:28]=[C:27]1[C:37]#[N:38])[CH:24]=[CH2:25]

参加物

5

反応物 3

HCID 468307945-bromo-1-(4-fluorophenyl)-1H-indazoleHCID 594372991-allyl-4-(2,2,2-trifluoro-acetyl)-1H-pyrrole-2-carbonitrileHCID 178418339Butyllithium

生成物 1

HCID 594372451-Allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carbonitrile収率 67%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a chilled (−78° C.) solution of 5-bromo-1-(4-fluorophenyl)-1H-indazole (1.3 g, 4.3 mmol, 1.1 equiv.) in 20 mL of THF was added n-BuLi (2.5 M in hexanes, 1.7 ml, 4.3 mmol, 1.1 equiv.) followed by a chilled (−78° C.) solution of 1-allyl-4-(2,2,2-trifluoroacetyl)-1H-pyrrole-2-carbonitrile (0.9 g, 3.9 mmol, 1 equiv.) in 3 mL of THF. After 30 minutes, the mixture was warmed to 0° C., quenched with water, diluted with brine, and extracted with EtOAc. The combined organics were dried, filtered, and concentrated in vacuo. The residue was purified by flash chromatography using EtOAc-hexanes (5-30% gradient) to afford 1.15 g (66%) of the title compound as an off-white solid. MS m/z 441.26 (MH+).

後処理

  1. customquenched with water
  2. additiondiluted with brine
  3. extractionextracted with EtOAc
  4. customThe combined organics were dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography

出典と根拠

ORDレコード
ord-dd13b837909b47d59d23bb7d4a3259bb
出典データセット
uspto-grants-2014_02
特許番号
US08658637B2

反応ノート

読み込み中…