Potassium Carbonate → 2-[4-[2-(5,6-difluorobenzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(2,2,2-trifluoroethoxy)-6-methyl-3-pyridyl]acetamide

HRID 1354257Notes

Reaction equation

HRID 1354257 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[C:40]([F:41])=[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.C(=O)([O-])[O-].[K+].[K+].Br[CH2:49][C:50]([NH:52][C:53]1[C:54]([O:66][CH2:67][C:68]([F:71])([F:70])[F:69])=[N:55][C:56]([CH3:65])=[CH:57][C:58]=1[O:59][CH2:60][C:61]([F:64])([F:63])[F:62])=[O:51]>C(#N)C.O>[F:22][C:23]1[C:40]([F:41])=[CH:39][C:26]2[N:27]=[C:28]([S:30][CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][N:36]([CH2:49][C:50]([NH:52][C:53]4[C:54]([O:66][CH2:67][C:68]([F:71])([F:69])[F:70])=[N:55][C:56]([CH3:65])=[CH:57][C:58]=4[O:59][CH2:60][C:61]([F:63])([F:64])[F:62])=[O:51])[CH2:35][CH2:34]3)[NH:29][C:25]=2[CH:24]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 115899302-bromo-N-[2,4-bis(2,2,2-trifluoroethoxy)-6-methylpyridin-3-yl]acetamideHCID 230924391-[2-(5,6-Difluorobenzimidazol-2-ylthio)ethyl]piperazine tris(trifluoroacetic acid) salt

Product 1

HCID 100097592-[4-[2-(5,6-difluorobenzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(2,2,2-trifluoroethoxy)-6-methyl-3-pyridyl]acetamideYield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

1-[2-(5,6-Difluorobenzimidazol-2-ylthio)ethyl]piperazine tris(trifluoroacetic acid) salt (4.00 g, 6.25 mmol) and potassium carbonate (31.26 mmol) were dissolved in acetonitrile (100 mL) and water (30 mL). While the solution was stirred under cooling with ice, 2-bromo-N-[2,4-bis(2,2,2-trifluoroethoxy)-6-methylpyridin-3-yl]acetamide (2.20 g, 5.22 mmol) was added thereto over 15 minutes. The temperature of the mixture was allowed to room temperature, and the mixture was stirred for 15 hours. Thereafter, the reaction mixture was diluted with water and then extracted with chloroform. 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 (silica gel 150 g, hexane: acetone=4:1 to 2:1 to 1:1). The thus-obtained crystals were recrystallized from chloroform-hexane, to thereby yield 2-[4-[2-(5,6-difluorobenzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(2,2,2-trifluoroethoxy)-6-methylpyridin-3-yl]acetamide (3.04 g, yield 91%) as a pale yellow powder.

Workup

  1. additionwas added
  2. customwas allowed to room temperature
  3. stirringthe mixture was stirred for 15 hours
  4. extractionextracted with chloroform
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over sodium sulfate anhydrate
  7. concentrationfollowed by concentration under reduced pressure
  8. customThe residue was purified through silica gel column chromatography (silica gel 150 g, hexane: acetone=4:1 to 2:1 to 1:1)
  9. customThe thus-obtained crystals were recrystallized from chloroform-hexane

Sources & evidence

ORD record
ord-4c16a04191174a89b77c9945479f6ad6
Source dataset
uspto-grants-2007_05
Patent number
US07223764B2

Reaction notes

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