Trifluoroacetic acid → 2-[{5-Fluoro-7-[(methylsulfanyl)methyl]-1H-indol-3-yl}(4-methylphenyl)methyl]cyclopropane-carbonitrile
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][CH3:24])[CH:21]=1)[NH:18][CH:17]=[CH:16]2.O[CH:26]([C:32]1[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=1)[CH:27]1[CH2:29][CH:28]1[C:30]#[N:31]>ClCCl>[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[C:20]([CH2:22][S:23][CH3:24])[CH:21]=1)[NH:18][CH:17]=[C:16]2[CH:26]([C:32]1[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=1)[CH:27]1[CH2:29][CH:28]1[C:30]#[N:31]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
130 mg (0.59 mmol) of indium(III) chloride and 0.05 ml (0.64 mmol) of trifluoroacetic acid were added to 104 mg (0.53 mmol) of the compound from Example 11A and 100 mg (0.53 mmol) of the compound from Example 158A in 6 ml of dichloromethane, and the mixture was stirred under reflux for 1 h. It was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate solution and water, 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 39.6 mg (20% of theory) of the title compound as mixture of diastereomers.
Workup
- temperatureunder reflux for 1 h
- washwashed with saturated aqueous sodium bicarbonate solution and water
- 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-fad44e7a140243f39ad8d640476a6c1c
- Source dataset
- uspto-grants-2011_11
- Patent number
- US08063234B2
Reaction notes
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