Cyclopentanone → HCID 86662302, compound

HRID 2364078Notes

Reaction equation

HRID 2364078 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([NH2:9])=[O:8])=[C:4]([NH:10][CH2:11][CH:12]([F:14])[F:13])[CH:3]=1.[C:15]1(=O)[CH2:19][CH2:18][CH2:17][CH2:16]1.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=O.[Na+].[CH3:47][C:48]1[C:52](B2OC(C)(C)C(C)(C)O2)=[CH:51][N:50](C(OC(C)(C)C)=O)[N:49]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.COCCOC.CC(N(C)C)=O>[F:13][CH:12]([F:14])[CH2:11][N:10]1[C:4]2[CH:3]=[C:2]([C:52]3[CH:51]=[N:50][NH:49][C:48]=3[CH3:47])[S:6][C:5]=2[C:7](=[O:8])[NH:9][C:15]21[CH2:19][CH2:18][CH2:17][CH2:16]2

Participants

11

Reactant 7

HCID 8452CyclopentanoneHCID 10340Sodium CarbonateHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 53216815Tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrazole-1-carboxylateHCID 866622985-Bromo-3-[(2,2-difluoroethyl)amino]thiophene-2-carboxamide

Product 1

HCID 86662302HCID 86662302, compoundYield 16%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 5-bromo-3-[(2,2-difluoroethyl)amino]thiophene -2-carboxamide (150 mg, 0.53 mmol), cyclopentanone (2.0 mL), CSA (12 mg, 0.053 mmol), MgSO4 (100 mg) and DMA (1 mL) was stirred at 110° C. for 20 h. The mixture was poured into saturated aqueous NaHCO3. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, hexane to 80:20 hexane/EtOAc) to give a brown crystalline solid. A flask was charged with this solid, 1,2-dimethoxyethane (4 mL), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (370 mg, 1.20 mmol), sodium carbonate (120 mg, 2.00 mmol) and water (2 mL). The flask was purged with argon. Then, 1,1′-bis(diphenylphosphino) ferrocenepalladium (II) dichloride dichloromethane adduct (33 mg, 0.040 mmol) was added to the mixture. The flask was purged with argon. After stirring at 100° C. for 2 h, 8 M aqueous NaOH (1.0 mL) was added. After stirring at 100° C. for 30 min, organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, 80:20 hexane/EtOAc to EtOAc), then crystallized from heptanes/EtOAc to give the title compound (29 mg, 16%) as a yellow solid:

Workup

  1. extractionThe organic materials were extracted with EtOAc
  2. washThe combined extracts were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customAfter removal of the solvent at reduced pressure
  6. customthe residue was purified by column chromatography (Purif, silica gel, hexane to 80:20 hexane/EtOAc)
  7. customto give a brown crystalline solid
  8. customThe flask was purged with argon
  9. customThe flask was purged with argon
  10. stirringAfter stirring at 100° C. for 2 h
  11. addition8 M aqueous NaOH (1.0 mL) was added
  12. stirringAfter stirring at 100° C. for 30 min
  13. extractionorganic materials were extracted with EtOAc
  14. washThe combined extracts were washed with brine
  15. dry with materialdried over Na2SO4
  16. filtrationfiltered
  17. customAfter removal of the solvent at reduced pressure
  18. customthe residue was purified by column chromatography (Purif, silica gel, 80:20 hexane/EtOAc to EtOAc)
  19. customcrystallized from heptanes/EtOAc

Sources & evidence

ORD record
ord-ea684c823b9b40bdb9d47063de0eacf3
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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