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2-(3-(Trifluoromethyl)benzyl)malonic acid → (2,4-Dichloro-8-methyl-3-(3-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

HRID 1507315
ノート
印刷プレビュー

反応式

HRID 1507315 の反応式
[Cl:1][C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16](S(C)(=O)=O)=[CH:15][CH:14]=2)=[C:10]([Cl:23])[C:9]2[C:4](=[C:5]([CH3:32])[CH:6]=[C:7]([C:24]([C:26]3[N:30]([CH3:31])[CH:29]=[N:28][CH:27]=3)=[O:25])[CH:8]=2)[N:3]=1.[F:33][C:34]([F:50])([F:49])C1C=C(C=CC=1)CC(C(O)=O)C(O)=O>O=P(Cl)(Cl)Cl>[Cl:1][C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:34]([F:50])([F:49])[F:33])[CH:14]=2)=[C:10]([Cl:23])[C:9]2[C:4](=[C:5]([CH3:32])[CH:6]=[C:7]([C:24]([C:26]3[N:30]([CH3:31])[CH:29]=[N:28][CH:27]=3)=[O:25])[CH:8]=2)[N:3]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 665199072-(3-(Trifluoromethyl)benzyl)malonic acid2 回HCID 86715618(2,4-dichloro-8-methyl-3-(4-(methylsulfonyl)benzyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone2 回

生成物 1

HCID 118005810(2,4-Dichloro-8-methyl-3-(3-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

試薬・触媒・溶媒 1

HCID 24813Phosphorus oxychloride溶媒

反応条件

温度
105 °C

実験手順

A heterogeneous mixture of (4-amino-3-methylphenyl)(1-methyl-1H-imidazol-5-yl)methanone (1.3 g, 6.04 mmol, Intermediate 13: step c), 2-(3-(trifluoromethyl)benzyl)malonic acid (2.06 g, 7.85 mmol, Intermediate 15: step b) and POCl3 (10 mL) was heated at 105° C. for 4 hours. The mixture was cooled to room temperature and concentrated to remove excess POCl3. Ice water was then added and the mixture treated with aqueous NH4OH (kept adding ice during addition) to a basic pH 8-9. The aqueous mixture was extracted with EtOAc (2×). The EtOAc extracts were dried over Na2SO4, evaporated in vacuo and chromatographed (DCM/EtOAc, gradient) to provide the title compound as an off-white solid.

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated
  3. customto remove excess POCl3
  4. additionIce water was then added
  5. additionthe mixture treated with aqueous NH4OH (kept adding ice during addition) to a basic pH 8-9
  6. extractionThe aqueous mixture was extracted with EtOAc (2×)
  7. dry with materialThe EtOAc extracts were dried over Na2SO4
  8. customevaporated in vacuo
  9. customchromatographed (DCM/EtOAc, gradient)

出典と根拠

ORDレコード
ord-805e275fc19243b892081fa3c867e471
出典データセット
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09221804B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート