Water → 2-[4-[2-(5-fluorobenzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(2,2,2-trifluoroethoxy)-6-methylpyridin-3-yl]acetamide

HRID 1354262Notes

Reaction equation

HRID 1354262 reaction equation
FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[F:22][C:23]1[CH:40]=[CH:39][C:26]2[N:27]=[C:28]([S:30][CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)[NH:29][C:25]=2[CH:24]=1.Br[CH2:42][C:43]([NH:45][C:46]1[C:47]([O:59][CH2:60][C:61]([F:64])([F:63])[F:62])=[N:48][C:49]([CH3:58])=[CH:50][C:51]=1[O:52][CH2:53][C:54]([F:57])([F:56])[F:55])=[O:44].C(=O)([O-])[O-].[K+].[K+].O>C(#N)C>[F:22][C:23]1[CH:40]=[CH:39][C:26]2[N:27]=[C:28]([S:30][CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][N:36]([CH2:42][C:43]([NH:45][C:46]4[C:47]([O:59][CH2:60][C:61]([F:64])([F:62])[F:63])=[N:48][C:49]([CH3:58])=[CH:50][C:51]=4[O:52][CH2:53][C:54]([F:56])([F:57])[F:55])=[O:44])[CH2:35][CH2:34]3)[NH:29][C:25]=2[CH:24]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 115899302-bromo-N-[2,4-bis(2,2,2-trifluoroethoxy)-6-methylpyridin-3-yl]acetamideHCID 231161601-[2-(5-Fluorobenzimidazol-2-ylthio)ethyl]piperazine tris(trifluoroacetic acid) salt

Product 1

HCID 231161592-[4-[2-(5-fluorobenzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(2,2,2-trifluoroethoxy)-6-methylpyridin-3-yl]acetamideYield 71.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-[2-(5-Fluorobenzimidazol-2-ylthio)ethyl]piperazine tris(trifluoroacetic acid) salt (6.92 g, 11.12 mmol) and 2-bromo-N-[2,4-bis(2,2,2-trifluoroethoxy)-6-methylpyridin-3-yl]acetamide (4.50 g, 10.59 mmol) were suspended in acetonitrile (90 mL), and potassium carbonate (5.85 g, 42.33 mmol) was gradually added to the suspension. The mixture was stirred for five hours at room temperature, and water (100 mL) was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and then dried over sodium sulfate anhydrate, followed by concentration under reduced pressure. The residue was purified through silica gel column chromatography (chloroform:methanol=50:1). The thus-obtained crystals were recrystallized from acetone-ether, to thereby yield 2-[4-[2-(5-fluorobenzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(2,2,2-trifluoroethoxy)-6-methylpyridin-3-yl]acetamide (4.72 g, yield 71%) as pale brown prisms.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over sodium sulfate anhydrate
  4. concentrationfollowed by concentration under reduced pressure
  5. customThe residue was purified through silica gel column chromatography (chloroform:methanol=50:1)
  6. customThe thus-obtained crystals were recrystallized from acetone-ether

Sources & evidence

ORD record
ord-c8e27f70f14e42cfa0ac697fcd8e5e30
Source dataset
uspto-grants-2007_05
Patent number
US07223764B2

Reaction notes

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