Trifluoroacetic acid → 2-[(4-Chloro-2-fluorophenyl){7-[(methylsulfonyl)methyl]-1H-indol-3-yl}methyl]cyclopropane-carbonitrile

HRID 561693노트

반응식

HRID 561693 반응식
[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]([F:26])[CH:14]=1.[CH3:27][S:28]([CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[C:36]2[C:40]=1[NH:39][CH:38]=[CH:37]2)(=[O:30])=[O:29]>ClCCl>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([C:37]2[C:36]3[C:40](=[C:32]([CH2:31][S:28]([CH3:27])(=[O:30])=[O:29])[CH:33]=[CH:34][CH:35]=3)[NH:39][CH:38]=2)[CH:20]2[CH2:22][CH:21]2[C:23]#[N:24])=[C:15]([F:26])[CH:14]=1

참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583922222-[(4-Chloro-2-fluorophenyl)(hydroxy)methyl]cyclopropanecarbonitrileHCID 583922947-[(Methylsulfonyl)methyl]-1H-indole

생성물 1

HCID 583922862-[(4-Chloro-2-fluorophenyl){7-[(methylsulfonyl)methyl]-1H-indol-3-yl}methyl]cyclopropane-carbonitrile

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

1.76 g (7.98 mmol) of indium(III) chloride and 0.92 ml (12.0 mmol) of trifluoroacetic acid were added to 1.50 g (6.65 mmol) of the compound from Example 165A and 1.67 g (7.98 mmol) of the compound from Example 86A under argon in 69 ml of dichloromethane, 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) and another isocratic RP18 separation with acetonitrile/water 1:1 to result in 283 mg (10% of theory) of diastereomer 1 and 145 mg (5% 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)
  9. customanother isocratic RP18 separation with acetonitrile/water 1:1

출처 및 근거

ORD 기록
ord-0a6376f4034742a480ed9d8e35815822
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063234B2

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