Trifluoroacetic acid → 2-[1-(2,4-Difluorophenyl)-1-{7-[(methylsulfanyl)methyl]-1H-indol-3-yl}ethyl]cyclopropane-carbonitrile

HRID 561628Notes

Reaction equation

HRID 561628 reaction equation
FC(F)(F)C(O)=O.[Cl-].[In+3].[Cl-].[Cl-].[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C:20]([CH:23]1[CH2:25][CH:24]1[C:26]#[N:27])(O)[CH3:21].[CH3:28][S:29][CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[C:35]2[C:39]=1[NH:38][CH:37]=[CH:36]2>ClCCl>[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C:20]([CH:23]1[CH2:25][CH:24]1[C:26]#[N:27])([C:36]1[C:35]2[C:39](=[C:31]([CH2:30][S:29][CH3:28])[CH:32]=[CH:33][CH:34]=2)[NH:38][CH:37]=1)[CH3:21]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583921877-[(Methylsulfanyl)methyl]-1H-indoleHCID 583921942-[1-(2,4-Difluorophenyl)-1-hydroxyethyl]cyclopropanecarbonitrile

Product 1

HCID 583924332-[1-(2,4-Difluorophenyl)-1-{7-[(methylsulfanyl)methyl]-1H-indol-3-yl}ethyl]cyclopropane-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

0.08 ml (1.08 mmol) of trifluoroacetic acid and 218 mg (0.99 mmol) of indium(III) chloride were added to 200 mg (0.90 mmol) of the compound from Example 133A and 318 mg (1.79 mmol) of the compound from Example 8A in 8 ml of dichloromethane at RT, 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 128 mg (37% 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-4e8c5c8d9abd428d9ecd75fdadd46643
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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