Trifluoroacetic acid → 2-[(4-Methylphenyl){7-[(methylsulfonyl)methyl]-1H-indol-3-yl}methyl]cyclopropanecarbonitrile
Reaction equation
[Cl-].[In+3].[Cl-].[Cl-].FC(F)(F)C(O)=O.[CH3:12][S:13]([CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[C:25]=1[NH:24][CH:23]=[CH:22]2)(=[O:15])=[O:14].O[CH:27]([C:33]1[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=1)[CH:28]1[CH2:30][CH:29]1[C:31]#[N:32]>ClCCl>[CH3:39][C:36]1[CH:37]=[CH:38][C:33]([CH:27]([C:22]2[C:21]3[C:25](=[C:17]([CH2:16][S:13]([CH3:12])(=[O:15])=[O:14])[CH:18]=[CH:19][CH:20]=3)[NH:24][CH:23]=2)[CH:28]2[CH2:30][CH:29]2[C:31]#[N:32])=[CH:34][CH:35]=1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
195 mg (0.88 mmol) of indium(III) chloride and 0.11 ml (1.44 mmol) of trifluoroacetic acid were added to 168 mg (0.80 mmol) of the compound from Example 86A and 150 mg (0.80 mmol) of the compound from Example 158A under argon in 9 ml of dichloromethane, and the mixture was heated under reflux for 1 h. 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 100 mg (33% of theory) of the title compound as mixture of diastereomers.
Workup
- temperaturethe mixture was heated
- temperatureunder reflux for 1 h
- washwashed with water and saturated aqueous sodium bicarbonate solution
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- 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-d83169ba98bf44bd8bd7efec78c4fb48
- Source dataset
- uspto-grants-2011_11
- Patent number
- US08063234B2
Reaction notes
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