p-Toluenesulfonic acid → HCID 66743650, compound

HRID 2364005Notes

Reaction equation

HRID 2364005 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([NH2:9])=[O:8])=[C:4]([NH:10][CH3:11])[CH:3]=1.[F:12][C:13]([F:18])([F:17])[C:14]([CH3:16])=O.CC1C=CC(S(O)(=O)=O)=CC=1.[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=O.[Na+].C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:55]2[CH:56]=[N:57][NH:58][CH:59]=2)O1>O.COCCOC.CN(C=O)C>[CH3:11][N:10]1[C:4]2[CH:3]=[C:2]([C:55]3[CH:56]=[N:57][NH:58][CH:59]=3)[S:6][C:5]=2[C:7](=[O:8])[NH:9][C:14]1([CH3:16])[C:13]([F:18])([F:17])[F:12]

Participants

11

Reactant 7

HCID 6101p-Toluenesulfonic acidHCID 9871Methyl trifluoromethyl ketoneHCID 10340Sodium CarbonateHCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 66743363HCID 66743363, compound

Product 1

HCID 66743650HCID 66743650, compoundYield 9.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 5-bromo-3-(methylamino)thiophene-2-carboxamide (235 mg, 1.00 mmol), 1,1,1-trifluoroacetone (2.00 mL, 22.3 mmol), PTSA (19.0 mg, 0.100 mmol), MgSO4 (120 mg, 1.00 mmol) and DMF (2 mL) was microwave-irradiated at 130° C. for 2 h then at 140° C. for 4 h. Then, the mixture was poured into saturated aqueous NaHCO3 (100 mL). Extraction with EtOAc (100 mL×2), washing with brine, drying over MgSO4, filtration and concentration under reduced pressure gave a dark solid. This residue was mixed with sodium carbonate (530 mg, 5.00 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (582 mg, 3.00 mmol), 1,2-dimethoxyethane (2.5 mL) and water (5 mL). The mixture was purged with argon. Then, 1,1′-bis (diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (82 mg, 0.10 mmol) was added, and the mixture was purged with argon again. This mixture was refluxed overnight. Then, the mixture was poured into saturated aqueous NaHCO3 and extracted with EtOAc, and the extract was dried over MgSO4, filtered and concentrated at reduced pressure to give a dark oil. This residue was purified by column chromatography (Purif, silica gel, hexane to EtOAc) to give a dark solid (29 mg). This solid was triturated with EtOAc/hexane and collected by filtration to afford the title compound (13.6 mg, 4.3%) as a beige solid:

Workup

  1. customwas microwave-irradiated at 130° C. for 2 h
  2. extractionExtraction with EtOAc (100 mL×2)
  3. washwashing with brine
  4. dry with materialdrying over MgSO4, filtration and concentration under reduced pressure
  5. customgave a dark solid
  6. customThe mixture was purged with argon
  7. customthe mixture was purged with argon again
  8. temperatureThis mixture was refluxed overnight
  9. additionThen, the mixture was poured into saturated aqueous NaHCO3
  10. extractionextracted with EtOAc
  11. dry with materialthe extract was dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated at reduced pressure
  14. customto give a dark oil
  15. customThis residue was purified by column chromatography (Purif, silica gel, hexane to EtOAc)

Sources & evidence

ORD record
ord-93747082f44b452787643ff7dfc58bb9
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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