2,2-Dimethoxypropane → HCID 66743611, compound

HRID 2364067Notes

Reaction equation

HRID 2364067 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([NH2:9])=[O:8])=[C:4]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[CH:3]=1.CO[C:23](OC)([CH3:25])[CH3:24].CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[O-]S([O-])(=O)=O.[Mg+2].C(=O)([O-])O.[Na+].[CH3:54][C:55]1[C:59](B2OC(C)(C)C(C)(C)O2)=[CH:58][N:57](C(OC(C)(C)C)=O)[N:56]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.COCCOC.CC(N(C)C)=O>[CH3:24][C:23]1([CH3:25])[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:4]2[CH:3]=[C:2]([C:59]3[CH:58]=[N:57][NH:56][C:55]=3[CH3:54])[S:6][C:5]=2[C:7](=[O:8])[NH:9]1

Participants

11

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 66743752HCID 66743752, compound

Product 1

HCID 66743611HCID 66743611, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromo-3-[(3-nitrobenzyl)amino]thiophene-2-carboxamide (260 mg, 0.730 mmol), 2,2-dimethoxypropane (2.0 mL), CSA (17 mg, 0.073 mmol), MgSO4 (200 mg) and DMA (2 mL) was microwave-irradiated at 120° C. for 1 h. Then, saturated aqueous sodium hydrogen carbonate was 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 yellow crystalline solid was obtained. 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 (675 mg, 2.19 mmol), sodium carbonate (219 mg, 3.65 mmol) and water (2 mL). The flask was purged with argon. Then, 1,1′-bis(diphenylphosphino) ferrocenepalladium (II) dichloride dichloromethane adduct (60 mg, 0.073 mmol) was added to the mixture. The flask was purged with argon again. After stirring at 100° C. for 2 h, 8 M aqueous NaOH (1.0 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 MeOH/EtOAo/hexane to give the title compound (124 mg, 43%) as a yellow solid:

Workup

  1. customwas microwave-irradiated at 120° C. for 1 h
  2. customto quench
  3. customthe reaction
  4. extractionThe organic materials were extracted with EtOAc
  5. washThe combined extracts were washed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customAfter removal of the solvent at reduced pressure
  9. customa yellow crystalline solid was obtained
  10. customThe flask was purged with argon
  11. customThe flask was purged with argon again
  12. addition8 M aqueous NaOH (1.0 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 MeOH/EtOAo/hexane

Sources & evidence

ORD record
ord-8fa07b71d58945a28c2d64e0a1f4c1e2
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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