2-Bromo-6-chloroquinoline → 4-((6-Chloroquinolin-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile

HRID 2104975ノート

反応式

HRID 2104975 の反応式
Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:12])[CH:8]=2)[N:3]=1.[Li]CCCC.[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([O:38][CH:39]([CH3:41])[CH3:40])[C:24]([F:37])=[C:25]([CH:36]=1)/[CH:26]=[N:27]/[C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=1)[CH3:19]>C1COCC1>[Cl:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([N:27]([CH2:26][C:25]1[CH:36]=[C:21]([O:20][CH2:18][CH3:19])[CH:22]=[C:23]([O:38][CH:39]([CH3:41])[CH3:40])[C:24]=1[F:37])[C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][CH:29]=1)[CH:11]=[CH:10]2

参加物

5

反応物 3

HCID 179335232-Bromo-6-chloroquinolineHCID 178418339ButyllithiumHCID 178466720HCID 178466720、化合物

生成物 1

HCID 688168234-((6-Chloroquinolin-2-yl)(5-ethoxy-2-fluoro-3-isopropoxyphenyl)methylamino)benzonitrile収率 55.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a solution of Intermediate 90.1 (100 mg, 0.412 mmol) in 2 mL THF at −78° C., was added BuLi (1.4 M in hexanes, 324 μL, 0.454 mmol). The mixture was stirred at −78° C. for 10 min, then a solution of Intermediate 7.3 (134 mg, 0.412 mmol) in 0.7 mL THF was added. The mixture was stirred 15 min at −78° C., allowed to warm to rt over 30 min, then was quenched with sat. NH4Cl and diluted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 30% EtOAc/hexanes gradient) to afford 112 mg of Intermediate 90.2 as a pale orange solid.

後処理

  1. stirringThe mixture was stirred 15 min at −78° C.
  2. temperatureto warm to rt over 30 min
  3. customwas quenched with sat. NH4Cl
  4. additiondiluted with EtOAc
  5. washThe organic phase was washed with H2O and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (0 to 30% EtOAc/hexanes gradient)

出典と根拠

ORDレコード
ord-16f243183ca04a0c88f82602f26104ca
出典データセット
uspto-grants-2009_08
特許番号
US07576098B2

反応ノート

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