Trifluoroacetic acid → 2-({7-[(Methylsulfonyl)methyl]-1H-indol-3-yl}[4-(trifluoromethyl)phenyl]methyl)cyclopropane-carbonitrile

HRID 561684Notes

Reaction equation

HRID 561684 reaction equation
[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].[CH3:29][S:30]([CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[C:38]2[C:42]=1[NH:41][CH:40]=[CH:39]2)(=[O:32])=[O:31]>ClCCCl.ClCCl>[CH3:29][S:30]([CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[C:38]2[C:42]=1[NH:41][CH:40]=[C:39]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])(=[O:32])=[O:31]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583922947-[(Methylsulfonyl)methyl]-1H-indoleHCID 58392408HCID 58392408, compound

Product 1

HCID 583921232-({7-[(Methylsulfonyl)methyl]-1H-indol-3-yl}[4-(trifluoromethyl)phenyl]methyl)cyclopropane-carbonitrile

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

1.05 g (4.75 mmol) of indium(III) chloride and 0.55 ml (7.12 mmol) of trifluoroacetic acid were added to 954 mg (3.96 mmol) of the compound from Example 160A and 1.02 g (4.75 mmol) of the compound from Example 86A in 60 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 HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 197 mg (12% 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 HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid)

Sources & evidence

ORD record
ord-b8509878956b48ddaef4cf8b43e0086b
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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