Potassium Carbonate → 2-(3-((3-((4-(Piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)benzyl)thio)phenyl)acetic acid

HRID 926893

Reaction equation

HRID 926893 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][CH:41]=1)[C:6]([NH:8][C:9]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]2)=[CH:29][C:10]=1[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)[N:15]=1)=[O:12])=[O:7].C(=O)([O-])[O-].[K+].[K+].[SH:48][C:49]1[CH:50]=[C:51]([CH2:55][C:56]([OH:58])=[O:57])[CH:52]=[CH:53][CH:54]=1>CN(C=O)C>[N:33]1([C:30]2[CH:31]=[CH:32][C:9]([NH:8][C:6]([C:5]3[CH:4]=[C:3]([CH:41]=[CH:40][CH:39]=3)[CH2:2][S:48][C:49]3[CH:50]=[C:51]([CH2:55][C:56]([OH:58])=[O:57])[CH:52]=[CH:53][CH:54]=3)=[O:7])=[C:10]([C:11](=[O:12])[NH:13][C:14]3[CH:18]=[CH:17][N:16]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:27])([F:28])[F:26])[CH:20]=4)[N:15]=3)[CH:29]=2)[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 35431562-(3-Mercaptophenyl)acetic acid2×HCID 665882652-(3-(chloromethyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide

Product 1

HCID 566445522-(3-((3-((4-(Piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)benzyl)thio)phenyl)acetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a round bottom flask was placed a solution of 2-(3-(chloromethyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide 21b (0.23 mmol, 1 equiv) in DMF (1.2 mL), potassium carbonate (127.1 mg, 0.92 mmol, 4 equiv), and (3-mercaptophenyl)acetic acid (42.6 mg, 0.253 mmol, 1.1 equiv). The solution was stirred overnight at room temperature. The reaction progress was monitored by LCMS. After 16.5 h, more (3-mercaptophenyl)acetic acid (7 mg) was added to the solution, and the solution was stirred another 1 h. The solvent was removed. The residue was dissolved with DCM, washed with H2O and brine, and dried over sodium sulfate. The product was purified by reverse phase HPLC, eluting with 0.05% TFA in a water/acetonitrile gradient. MS (ES, m/z) 714 [M+H]+.

Workup

  1. customInto a round bottom flask was placed
  2. waitAfter 16.5 h
  3. stirringthe solution was stirred another 1 h
  4. customThe solvent was removed
  5. dissolutionThe residue was dissolved with DCM
  6. washwashed with H2O and brine
  7. dry with materialdried over sodium sulfate
  8. customThe product was purified by reverse phase HPLC
  9. washeluting with 0.05% TFA in a water/acetonitrile gradient

Sources & evidence

ORD record
ord-a524df3a1fac47e4bb75a546a8acf4ed
Source dataset
uspto-grants-2016_03
Patent number
US09289430B2

Linked notes

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