p-Toluenesulfonic acid → N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-oxo-2-(4-oxo-1-piperidyl)ethyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 529857Notes

Reaction equation

HRID 529857 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:38][CH:39]([F:41])[F:40])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:25][C:26]([N:28]3[CH2:37][CH2:36][C:31]4(OCC[O:32]4)[CH2:30][CH2:29]3)=[O:27])[N:9]=2)[CH:7]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:38][CH:39]([F:40])[F:41])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH2:25][C:26](=[O:27])[N:28]3[CH2:29][CH2:30][C:31](=[O:32])[CH2:36][CH2:37]3)[N:9]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 118523245N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-(1,4-dioxa-8-azaspiro[4,5]decan-8-yl)-2-oxo-ethyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

Product 1

HCID 118522668N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-oxo-2-(4-oxo-1-piperidyl)ethyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 45.3%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-(1,4-dioxa-8-azaspiro[4,5]decan-8-yl)-2-oxo-ethyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (1.01 g, 1.72 mmol) in acetone (20 mL) was added p-toluenesulfonic acid (359 mg, 2.06 mmol) and refluxed for 6 hours. LC/MS (method 31) shows product and presence of minor amounts of starting material. The reaction was cooled to room temperature and quenched with water. This was then extracted with ethyl acetate, dried with solid anhydrous magnesium sulfate powder and filtered to give a red oil. This was then purified by ISCO with a silica column and eluted with 0-15% methanol in dichloromethane to afford 0.43 g (0.78 mmol) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-oxo-2-(4-oxo-1-piperidyl)ethyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a foamy off white solid. LC/MS (method 39) [M+H]+=544.1, RT=1.91 min.

Workup

  1. temperaturerefluxed for 6 hours
  2. customquenched with water
  3. extractionThis was then extracted with ethyl acetate
  4. dry with materialdried with solid anhydrous magnesium sulfate powder
  5. filtrationfiltered
  6. customto give a red oil
  7. customThis was then purified by ISCO with a silica column
  8. washeluted with 0-15% methanol in dichloromethane

Sources & evidence

ORD record
ord-6d4b12b52c04418d9343b681ee15573f
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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