Trifluoroacetic acid → 2-[1-(2,4-Difluorophenyl)-1-{5-fluoro-7-[(methylsulfanyl)methyl]-1H-indol-3-yl}ethyl]cyclopropanecarbonitrile

HRID 561645Notes

Reaction equation

HRID 561645 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.[F:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[C:33]([CH:36]1[CH2:38][CH:37]1[C:39]#[N:40])(O)[CH3:34]>ClCCl>[F:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[C:33]([CH:36]1[CH2:38][CH:37]1[C:39]#[N:40])([C:16]1[C:15]2[C:19](=[C:20]([CH2:22][S:23][CH3:24])[CH:21]=[C:13]([F:12])[CH:14]=2)[NH:18][CH:17]=1)[CH3:34]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583921942-[1-(2,4-Difluorophenyl)-1-hydroxyethyl]cyclopropanecarbonitrileHCID 583922275-Fluoro-7-[(methylsulfanyl)methyl]-1H-indole

Product 1

HCID 445953822-[1-(2,4-Difluorophenyl)-1-{5-fluoro-7-[(methylsulfanyl)methyl]-1H-indol-3-yl}ethyl]cyclopropanecarbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

273 mg (1.23 mmol) of indium(III) chloride and 0.1 ml (1.34 mmol) of trifluoroacetic acid were added to 250 mg (1.12 mmol) of the compound from Example 11A and 437 mg (2.24 mmol) of the compound from Example 133A were introduced into 44 ml of dichloromethane, and the mixture was stirred at RT overnight. The reaction mixture was concentrated in a rotary evaporator. The residue was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 313 mg (69% of theory) of the title compound as mixture of diastereomers.

Workup

  1. concentrationThe reaction mixture was concentrated in a rotary evaporator
  2. 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-27c2191246e04da7a5f6f41b0cc9761f
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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