Trifluoroacetic acid → 2-({5-Fluoro-7-[(methylsulfonyl)methyl]-1H-indol-3-yl}[4-(trifluoromethyl)phenyl]methyl)cyclopropanecarbonitrile

HRID 561691노트

반응식

HRID 561691 반응식
[Cl-].[In+3].[Cl-].[Cl-].FC(F)(F)C(O)=O.O[CH:13]([C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=1)[CH:14]1[CH2:16][CH:15]1[C:17]#[N:18].[F:29][C:30]1[CH:31]=[C:32]2[C:36](=[C:37]([CH2:39][S:40]([CH3:43])(=[O:42])=[O:41])[CH:38]=1)[NH:35][CH:34]=[CH:33]2>ClCCCl>[F:29][C:30]1[CH:31]=[C:32]2[C:36](=[C:37]([CH2:39][S:40]([CH3:43])(=[O:41])=[O:42])[CH:38]=1)[NH:35][CH:34]=[C:33]2[CH:13]([C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=1)[CH:14]1[CH2:16][CH:15]1[C:17]#[N:18]

참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583923185-Fluoro-7-[(methylsulfonyl)methyl]-1H-indoleHCID 583924082-{Hydroxy[4-(trifluoromethyl)phenyl]methyl}cyclopropanecarbonitrile

생성물 1

HCID 583925102-({5-Fluoro-7-[(methylsulfonyl)methyl]-1H-indol-3-yl}[4-(trifluoromethyl)phenyl]methyl)cyclopropanecarbonitrile

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

33.0 mg (0.15 mmol) of indium(III) chloride and 0.02 ml (0.22 mmol) of trifluoroacetic acid were added to 30.0 mg (0.12 mmol) of the compound from Example 160A and 41.4 mg (0.15 mmol) of the compound from Example 87A with a purity of 82% under argon in 1 ml of 1,2-dichloroethane, and the mixture was heated under reflux for three days. It was concentrated and the residue was taken up in ethyl acetate, washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 12.6 mg (23% of theory) of diastereomer 1 and 13.2 mg (24% of theory) of diastereomer 2 of the title compound.

후처리

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for three days
  3. concentrationIt was concentrated
  4. washwashed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid)

출처 및 근거

ORD 기록
ord-3a4376cbeb9242fb9bb63f64fdb5ea52
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063234B2

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