Pyrazole → HCID 178456573, compound

HRID 892100Notes

Reaction equation

HRID 892100 reaction equation
C([N:8]1[C:16]2[C:15]3=[N:17][CH:18]([CH2:20]OS(C)(=O)=O)[CH2:19][N:14]3[C:13](=[O:26])[N:12]([CH2:27][CH2:28][CH3:29])[C:11]=2[N:10]=[C:9]1[CH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1)C1C=CC=CC=1.[NH:35]1[CH:39]=[CH:38][CH:37]=[N:36]1.C(=O)([O-])[O-].[Cs+].[Cs+].C([O-])=O.[NH4+]>CN(C)C=O.[OH-].[OH-].[Pd+2]>[CH:30]1([C:9]2[NH:8][C:16]3[C:15]4=[N:17][CH:18]([CH2:20][C:39]5[CH:38]=[CH:37][NH:36][N:35]=5)[CH2:19][N:14]4[C:13](=[O:26])[N:12]([CH2:27][CH2:28][CH3:29])[C:11]=3[N:10]=2)[CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

7

Reactant 4

HCID 1048PyrazoleHCID 10796Cesium carbonateHCID 2723923Ammonium formateHCID 22239978HCID 22239978, compound

Product 1

HCID 178456573HCID 178456573, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

Compound 17 (100 mg, 0.21 mmol) obtained in Example 17 was dissolved in N,N-dimethylformamide (1 mL), to the solution were added pyrazole (28 mg, 0.42 mmol, 2.0 equivalents), and cesium carbonate (137 mg, 0.42 mmol, 2.0 equivalents) and the mixture was stirred at 120° C. for 2 hours. The reaction mixture was partitioned with ethyl acetate and water, and the organic layer was washed with water and dried over anhydrous magnesium sulfate. After the organic layer was concentrated, diethyl ether and hexane were added to the concentrate and the resulting white solid (66 mg) was collected by filtration. The resulting product was dissolved in methanol (1 mL), to the solution were added ammonium formate (132 mg, 2.10 mmol) and 20% palladium hydroxide/carbon (30 mg), and then the mixture was stirred under reflux with heating for 3 hours. The reaction mixture was filtered by using Celite and concentrated, then to the concentrate were added ammonium formate (150 mg) and 20% palladium hydroxide/carbon (50 mg), and the mixture was stirred under reflux with heating for 4 hours. The reaction mixture was filtered by using Celite and concentrated, and the residue was purified by silica gel column chromatography (chloroform:methanol=10:1) to obtain the title compound (40 mg, 52%) as a white solid.

Workup

  1. customThe reaction mixture was partitioned with ethyl acetate and water
  2. washthe organic layer was washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationAfter the organic layer was concentrated
  5. additiondiethyl ether and hexane were added to the
  6. concentrationconcentrate
  7. filtrationthe resulting white solid (66 mg) was collected by filtration
  8. dissolutionThe resulting product was dissolved in methanol (1 mL), to the solution
  9. stirringthe mixture was stirred
  10. temperatureunder reflux
  11. temperaturewith heating for 3 hours
  12. filtrationThe reaction mixture was filtered
  13. concentrationconcentrated
  14. additionto the concentrate were added ammonium formate (150 mg) and 20% palladium hydroxide/carbon (50 mg)
  15. stirringthe mixture was stirred
  16. temperatureunder reflux
  17. temperaturewith heating for 4 hours
  18. filtrationThe reaction mixture was filtered
  19. concentrationconcentrated
  20. customthe residue was purified by silica gel column chromatography (chloroform:methanol=10:1)

Sources & evidence

ORD record
ord-c16a68d624a3426b848e143d19ebb8eb
Source dataset
uspto-grants-2006_02
Patent number
US07005430B2

Reaction notes

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