1,2-Dimethoxyethane → HCID 46871772, compound

HRID 2364033Notes

Reaction equation

HRID 2364033 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([CH3:17])([CH2:12][C:13]([F:16])([F:15])[F:14])[N:5]([CH3:18])[C:4]=2[CH:3]=1.[CH3:19][C:20]1[C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][N:22](C(OC(C)(C)C)=O)[N:21]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[CH3:18][N:5]1[C:4]2[CH:3]=[C:2]([C:24]3[CH:23]=[N:22][NH:21][C:20]=3[CH3:19])[S:10][C:9]=2[C:8](=[O:11])[NH:7][C:6]1([CH3:17])[CH2:12][C:13]([F:16])([F:15])[F:14]

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 53216815Tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrazole-1-carboxylateHCID 66743871HCID 66743871, compound

Product 1

HCID 46871772HCID 46871772, compoundYield 50.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A flask was charged with 6-bromo-1,2-dimethyl-2-(2,2,2-trifluoroethyl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (420 mg, 1.22 mmol), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl -1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (1.13 g, 3.7 mmol), sodium carbonate (366 mg, 6.1 mmol), 1,2-dimethoxyethane (6 mL) and water (3 mL). The flask was purged with argon. Then, 1,1′-bis(diphenylphosphino) ferrocenepalladium (II) dichloride dichloromethane adduct (98 mg, 0.12 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 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/EtOAc/heptane) to give the title compound (212 mg, 50%) as a pale yellow solid:

Workup

  1. customThe flask was purged with argon
  2. customThe flask was purged with argon again
  3. addition8 M aqueous NaOH (1 mL) was added
  4. stirringAfter stirring at 100° C. for 1 h
  5. extractionthe organic materials were extracted with EtOAc
  6. washThe combined extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customAfter removal of the solvent at reduced pressure
  10. customthe residue was purified by column chromatography (Purif, silica gel, 80:20 hexane/EtOAc to EtOAc)
  11. customcrystallized from MeOH/EtOAc/heptane)

Sources & evidence

ORD record
ord-daf5e9737b944cca9114473bd19a3a72
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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