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Trifluoroacetic acid → 2-[(4-Chloro-2-methoxyphenyl){5-fluoro-7-[(methylsulfonyl)methyl]-1H-indol-3-yl}methyl]cyclopropanecarbonitrile

HRID 561687
ノート
印刷プレビュー

反応式

HRID 561687 の反応式
[Cl-].[In+3].[Cl-].[Cl-].FC(F)(F)C(O)=O.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19](O)[CH:20]2[CH2:22][CH:21]2[C:23]#[N:24])=[C:15]([O:26][CH3:27])[CH:14]=1.[F:28][C:29]1[CH:30]=[C:31]2[C:35](=[C:36]([CH2:38][S:39]([CH3:42])(=[O:41])=[O:40])[CH:37]=1)[NH:34][CH:33]=[CH:32]2.[Cl-].[NH4+]>ClCCCl>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([C:32]2[C:31]3[C:35](=[C:36]([CH2:38][S:39]([CH3:42])(=[O:40])=[O:41])[CH:37]=[C:29]([F:28])[CH:30]=3)[NH:34][CH:33]=2)[CH:20]2[CH2:22][CH:21]2[C:23]#[N:24])=[C:15]([O:26][CH3:27])[CH:14]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 6422Trifluoroacetic acidHCID 25517Ammonium ChlorideHCID 159675indium(III)chlorideHCID 583921672-[(4-Chloro-2-methoxyphenyl)(hydroxy)methyl]cyclopropanecarbonitrileHCID 583923185-Fluoro-7-[(methylsulfonyl)methyl]-1H-indole

生成物 1

HCID 58392176
2-[(4-Chloro-2-methoxyphenyl){5-fluoro-7-[(methylsulfonyl)methyl]-1H-indol-3-yl}methyl]cyclopropanecarbonitrile

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

104 mg (0.47 mmol) of indium(III) chloride and 0.05 ml (0.70 mmol) of trifluoroacetic acid were added to 93.0 mg (0.39 mmol) of the compound from Example 163A and 121 mg (0.47 mmol) of the compound from Example 87A with a purity of 88% under argon in 5 ml of 1,2-dichloroethane, and the mixture was heated under reflux for 2 h. Addition of the reaction mixture to saturated aqueous ammonium chloride solution was followed by extraction with dichloromethane, drying over magnesium sulfate, filtration and concentration. The residue was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 35.0 mg (20% of theory) of diastereomer 1 and 31.3 mg (18% of theory) of diastereomer 2 of the title compound.

後処理

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 h
  3. extractionwas followed by extraction with dichloromethane
  4. dry with materialdrying over magnesium sulfate, filtration and concentration
  5. customThe residue was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid)

出典と根拠

ORDレコード
ord-8f34963b4a224b85ae4f31117c1492ab
出典データセット
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08063234B2

反応ノート

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