Cesium carbonate → 4-{3-(5-Chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidine-1-carboxylic acid tert-butyl ester

HRID 529753Notes

Reaction equation

HRID 529753 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH:26]([F:28])[F:27])=[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][NH:10][N:9]=2)[CH:7]=1.[C:29]([O:33][C:34]([N:36]1[CH2:41][CH2:40][CH:39](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:38][CH2:37]1)=[O:35])([CH3:32])([CH3:31])[CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[C:29]([O:33][C:34]([N:36]1[CH2:41][CH2:40][CH:39]([N:10]2[CH:11]=[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])[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:25][CH:26]([F:28])[F:27])=[N:9]2)[CH2:38][CH2:37]1)=[O:35])([CH3:32])([CH3:30])[CH3:31]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 157347131-(tert-Butoxycarbonyl)-4-(p-toluenesulfonyloxy)piperidineHCID 178522413HCID 178522413, compound

Product 1

HCID 1185223724-{3-(5-Chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [3-(5-chloro-2-difluoromethoxyphenyl)-1H-pyrazol-4-yl]amide (200 mg, 0.49 mmol) was dissolved in DMF (5 mL), 4-(toluene-4-sulfonyloxy)piperidine-1-carboxylic acid tert-butyl ester (263 mg, 0.74 mmol) and cesium carbonate (240 mg, 0.74 mmol) were added and the mixture heated at 90° C. for 2 hours. The mixture was allowed to cool to room temperature, diluted with water and extracted with DCM (×3). The combined organic extract was washed with brine, dried (Na2SO4), filtered and evaporated. The resultant yellow oil was purified by flash chromatography on silica eluting with 0-2% MeOH in DCM. The appropriate fractions were collected and evaporated to afford 4-{3-(5-chloro-2-difluoromethoxyphenyl)-4-[(pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]pyrazol-1-yl}piperidine-1-carboxylic acid tert-butyl ester a yellow oil. The crude product was taken onto the next step without further purification. LCMS (Method 4) [M+Na]+=610.0; RT=4.30 min.

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with DCM (×3)
  3. extractionThe combined organic extract
  4. washwas washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe resultant yellow oil was purified by flash chromatography on silica eluting with 0-2% MeOH in DCM
  9. customThe appropriate fractions were collected
  10. customevaporated

Sources & evidence

ORD record
ord-6ae026a3acd24f1792c8fc0e7f350d07
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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