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

HRID 561690Notes

Reaction equation

HRID 561690 reaction equation
[Cl-].[In+3].[Cl-].[Cl-].FC(F)(F)C(O)=O.[F:12][C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=1[CH:23](O)[CH:24]1[CH2:26][CH:25]1[C:27]#[N:28].[F:30][C:31]1[CH:32]=[C:33]2[C:37](=[C:38]([CH2:40][S:41]([CH3:44])(=[O:43])=[O:42])[CH:39]=1)[NH:36][CH:35]=[CH:34]2>ClCCCl>[F:30][C:31]1[CH:32]=[C:33]2[C:37](=[C:38]([CH2:40][S:41]([CH3:44])(=[O:42])=[O:43])[CH:39]=1)[NH:36][CH:35]=[C:34]2[CH:23]([C:14]1[CH:15]=[CH:16][C:17]([C:19]([F:22])([F:21])[F:20])=[CH:18][C:13]=1[F:12])[CH:24]1[CH2:26][CH:25]1[C:27]#[N:28]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583921352-{[2-Fluoro-4-(trifluoromethyl)phenyl] (hydroxy)methyl}cyclopropanecarbonitrileHCID 583923185-Fluoro-7-[(methylsulfonyl)methyl]-1H-indole

Product 1

HCID 583925412-({5-Fluoro-7-[(methylsulfonyl)methyl]-1H-indol-3-yl}[2-fluoro-4-(trifluoro-methyl)phenyl]methyl)cyclopropanecarbonitrile

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1.63 g (7.35 mmol) of indium(III) chloride and 0.85 ml (11.0 mmol) of trifluoroacetic acid were added to 1.59 g (6.13 mmol) of the compound from Example 164A and 1.90 g (7.35 mmol) of the compound from Example 87A in 100 ml of 1,2-dichloroethane, and the mixture was heated under reflux overnight. It was concentrated and the residue was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 763 mg (27% of theory) of the title compound as mixture of diastereomers.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux overnight
  3. concentrationIt was concentrated
  4. customthe residue was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid)

Sources & evidence

ORD record
ord-2365e2f3ba3d4ba080e7febccdb3932f
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

Loading…