2,2-Dimethoxypropane → HCID 86662299, compound

HRID 2364053Notes

Reaction equation

HRID 2364053 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.CO[C:17](OC)([CH3:19])[CH3:18].CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=O.[Na+].[CH3:48][C:49]1[C:53](B2OC(C)(C)C(C)(C)O2)=[CH:52][N:51](C(OC(C)(C)C)=O)[N:50]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.COCCOC.CCOC(C)=O.CC(N(C)C)=O>[F:13][CH:12]([F:14])[CH2:11][N:10]1[C:4]2[CH:3]=[C:2]([C:53]3[CH:52]=[N:51][NH:50][C:49]=3[CH3:48])[S:6][C:5]=2[C:7](=[O:8])[NH:9][C:17]1([CH3:19])[CH3:18]

Participants

12

Reactant 7

HCID 64952,2-DimethoxypropaneHCID 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 86662299HCID 86662299, compoundYield 52%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 5-bromo-3-[(2,2-difluoroethyl)amino]thiophene-2-carboxamide (130 mg, 0.456 mmol), 2,2-dimethoxypropane (1 mL), CSA (11 mg, 0.046 mmol), MgSO4 (110 mg, 0.912 mmol) and DMA (1 mL) was stirred at 90° C. for 2 h. Then, saturated aqueous NaHCO3 and EtOAc were added to quench the reaction. 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, a colorless crystalline solid was obtained. A flask was charged with the solid, 1,2-dimethoxyethane (3.0 mL), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (422 mg, 1.37 mmol), sodium carbonate (137 mg, 2.28 mmol) and water (1.5 mL). The flask was purged with argon. Then, 1,1′-bis (diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (37 mg, 0.046 mmol) was added to the mixture. The flask was purged with argon. After stirring at 100° C. for 2 h, 8 M aqueous NaOH (0.5 mL) was added. After stirring at 100° C. for 1 h, the 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 EtOAc/hexane to give the title compound (78 mg, 52%) as a yellow solid:

Workup

  1. customto quench
  2. customthe reaction
  3. extractionThe organic materials were extracted with EtOAc
  4. washThe combined extracts were washed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customAfter removal of the solvent at reduced pressure
  8. customa colorless crystalline solid was obtained
  9. customThe flask was purged with argon
  10. customThe flask was purged with argon
  11. stirringAfter stirring at 100° C. for 2 h
  12. addition8 M aqueous NaOH (0.5 mL) was added
  13. stirringAfter stirring at 100° C. for 1 h
  14. extractionthe organic materials were extracted with EtOAc
  15. washThe combined extracts were washed with brine
  16. dry with materialdried over Na2SO4
  17. filtrationfiltered
  18. customAfter removal of the solvent at reduced pressure
  19. customthe residue was purified by column chromatography (Purif, silica gel, 80:20 hexane/EtOAc to EtOAc)
  20. customcrystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-8cbe7a8e64b24d6cbf34ddede8e5bd9a
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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