p-Toluenesulfonic acid → HCID 66743201, compound

HRID 2364028Notes

Reaction equation

HRID 2364028 reaction equation
Cl.Cl.[Br:3][C:4]1[C:5]([NH:17][CH3:18])=[C:6]([C:14]([NH2:16])=[O:15])[S:7][C:8]=1[C:9]1[CH:10]=[N:11][NH:12][CH:13]=1.C([O-])(O)=O.[Na+].[C:24]1(=O)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.CC1C=CC(S(O)(=O)=O)=CC=1.[O-]S([O-])(=O)=O.[Mg+2]>CN(C=O)C.CCOC(C)=O>[Br:3][C:4]1[C:5]2[N:17]([CH3:18])[C:24]3([CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)[NH:16][C:14](=[O:15])[C:6]=2[S:7][C:8]=1[C:9]1[CH:10]=[N:11][NH:12][CH:13]=1

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 7967CyclohexanoneHCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium Bicarbonate2×HCID 66743846HCID 66743846, compound

Product 1

HCID 66743201HCID 66743201, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-bromo-3-(methylamino)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide dihydrochloride (90 mg, 0.267 mmol), saturated aqueous NaHCO3 (50 mL) and EtOAc (50 mL) was shaken well. The organic layer was collected, dried over MgSO4, filtered and concentrated under reduced pressure. This residue was mixed with cyclohexanone (2.00 mL, 19.3 mmol), PTSA (93 mg, 0.491 mmol), MgSO4 (64.2 mg, 0.533 mmol) and DMF (2 mL). This mixture was stirred at 80° C. for 4 h. The mixture was poured into saturated aqueous NaHCO3 and extracted with 3:1 EtOAc/THF (100 mL), and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc) to afford a white solid. This solid was triturated with EtOAc, and the precipitate was collected by filtration to afford the title compound (46.2 mg, 46%) as a white solid:

Workup

  1. customThe organic layer was collected
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. stirringThis mixture was stirred at 80° C. for 4 h
  6. extractionextracted with 3:1 EtOAc/THF (100 mL)
  7. dry with materialthe extract was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc)
  11. customto afford a white solid
  12. customThis solid was triturated with EtOAc
  13. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-7e22edfa5fd144389ec42c8da0e5a73f
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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