Cesium carbonate → 2-Cyclopropyl-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol

HRID 1922156ノート

反応式

HRID 1922156 の反応式
Cl[C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:15][CH:14]=2)=[C:10]([CH3:24])[C:9]2[C:8]([OH:25])=[CH:7][CH:6]=[C:5]([F:26])[C:4]=2[N:3]=1.[CH:27]1(B(O)O)[CH2:29][CH2:28]1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>O>[CH:27]1([C:2]2[C:11]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][CH:14]=3)=[C:10]([CH3:24])[C:9]3[C:8]([OH:25])=[CH:7][CH:6]=[C:5]([F:26])[C:4]=3[N:3]=2)[CH2:29][CH2:28]1

参加物

6

反応物 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 2760897Cyclopropylboronic acidHCID 1363483602-Chloro-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol

生成物 1

HCID 1363483632-Cyclopropyl-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol収率 23.1%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
90 °C

実験手順

A mixture of 2-chloro-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol (0.26 g), cyclopropylboronic acid (0.12 g), caesium carbonate (0.92 g), dioxane (5.7 mL) and water (1.4 mL) was purged with argon, and then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (0.058 g). The mixture was heated at 90° C. for 3 hours, cooled to room temperature, neutralised with saturated aqueous ammonium chloride solution and extracted with ethyl acetate (3×20 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (5.0 mL), dried over magnesium sulfate and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (1:0 to 3:2 by volume) gave title compound as a yellow oil (0.061 g).

後処理

  1. customwas purged with argon
  2. additiontreated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (0.058 g)
  3. temperaturecooled to room temperature
  4. extractionextracted with ethyl acetate (3×20 mL)
  5. washThe combined extracts were washed with saturated aqueous sodium chloride solution (5.0 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customPurification of the residue by column chromatography on silica gel
  9. washeluting with a mixture of cyclohexane and ethyl acetate (1:0 to 3:2 by volume)

出典と根拠

ORDレコード
ord-93f3a879bbeb413e9fa5b6837cd7e1b0
出典データセット
uspto-grants-2012_05
特許番号
US08173812B2

反応ノート

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