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

HRID 561685Notes

Reaction equation

HRID 561685 reaction equation
[Cl-].[In+3].[Cl-].[Cl-].FC(F)(F)C(O)=O.[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[C:20]([CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[CH:21]=1)[NH:18][CH:17]=[CH:16]2.[Cl:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[CH:35](O)[CH:36]1[CH2:38][CH:37]1[C:39]#[N:40]>ClCCCl.ClCCl>[Cl:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[CH:35]([C:16]1[C:15]2[C:19](=[C:20]([CH2:22][S:23]([CH3:26])(=[O:24])=[O:25])[CH:21]=[C:13]([F:12])[CH:14]=2)[NH:18][CH:17]=1)[CH:36]1[CH2:38][CH:37]1[C:39]#[N:40]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583923185-Fluoro-7-[(methylsulfonyl)methyl]-1H-indoleHCID 583924412-[(2-Chloro-4-fluorophenyl)(hydroxy)methyl]cyclopropanecarbonitrile

Product 1

HCID 583923392-[(2-Chloro-4-fluorophenyl){5-fluoro-7-[(methylsulfonyl)methyl]-1H-indol-3-yl}methyl]cyclopropanecarbonitrile

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

1.62 g (7.31 mmol) of indium(III) chloride and 0.92 ml (12.0 mmol) of trifluoroacetic acid were added to 1.89 g (6.65 mmol) of the compound from Example 87A with a purity of 80% and 1.50 g (6.65 mmol) of the compound from Example 161A under argon in 75 ml of 1,2-dichloroethane, and the mixture was heated under reflux overnight. It was diluted with dichloromethane and washed with water and saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, filtered and concentrated. The residue was purified by preparative SFC HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 1.65 g (57% of theory) of the title compound as mixture of diastereomers.

Workup

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

Sources & evidence

ORD record
ord-f3c9b6e6f81a42d6936582ac617807bb
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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