Trifluoroacetic acid → 2-Methyl-2-({4-[2-({5-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl}amino)ethyl]-1,3-thiazol-2-yl}thio)propionic acid

HRID 914347Notes

Reaction equation

HRID 914347 reaction equation
C([O:5][C:6](=[O:36])[C:7]([CH3:35])([S:9][C:10]1[S:11][CH:12]=[C:13]([CH2:15][CH2:16][NH:17][C:18]2[N:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][C:27]([O:30][C:31]([F:34])([F:33])[F:32])=[CH:26][CH:25]=3)=[CH:20][N:19]=2)[N:14]=1)[CH3:8])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:35][C:7]([S:9][C:10]1[S:11][CH:12]=[C:13]([CH2:15][CH2:16][NH:17][C:18]2[N:23]=[CH:22][C:21]([C:24]3[CH:25]=[CH:26][C:27]([O:30][C:31]([F:34])([F:32])[F:33])=[CH:28][CH:29]=3)=[CH:20][N:19]=2)[N:14]=1)([CH3:8])[C:6]([OH:36])=[O:5]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 597590702-Methyl-2-({4-[2-({5-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl}amino)ethyl]-1,3-thiazol-2-yl}thio)propionic acid tert-butyl ester

Product 1

HCID 116915632-Methyl-2-({4-[2-({5-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl}amino)ethyl]-1,3-thiazol-2-yl}thio)propionic acidYield 89.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Methyl-2-({4-[2-({5-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl}amino)ethyl]-1,3-thiazol-2-yl}thio)propionic acid tert-butyl ester (370 mg) obtained in Example 162-2 was dissolved in dichloromethane (2 mL), trifluoroacetic acid (2 mL) was added, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed with saturated aqueous sodium hydrogen carbonate solution (the objective compound was extracted in the ethyl acetate layer). The ethyl acetate layer was washed with aqueous 10% citric acid solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=2:1 to 1:1) to give the title compound (297 mg) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, ethyl acetate
  2. additionwas added
  3. washthe mixture was washed with saturated aqueous sodium hydrogen carbonate solution (the objective compound
  4. extractionwas extracted in the ethyl acetate layer)
  5. washThe ethyl acetate layer was washed with aqueous 10% citric acid solution and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=2:1 to 1:1)

Sources & evidence

ORD record
ord-2dc5ec7efc5547728006245c9f0a127c
Source dataset
uspto-grants-2011_09
Patent number
US08026370B2

Reaction notes

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