1,2-Dimethoxyethane → tert-butyl (3S)-3-[6-(5-methyl-1H-pyrazol-4-yl)-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl]-2-azabicyclo[2.2.2]octane-2-carboxylate

HRID 1022937Notes

Reaction equation

HRID 1022937 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([C@@H:12]3[CH:17]4[CH2:18][CH2:19][CH:14]([CH2:15][CH2:16]4)[N:13]3[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[N:5][C:4]=2[CH:3]=1.[CH3:27][C:28]1[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][N:30](C(OC(C)(C)C)=O)[N:29]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[CH3:27][C:28]1[NH:29][N:30]=[CH:31][C:32]=1[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([C@@H:12]3[CH:17]4[CH2:18][CH2:19][CH:14]([CH2:15][CH2:16]4)[N:13]3[C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])=[N:5][C:4]=2[CH:3]=1

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 136333933tert-butyl (3S)-3-(6-bromo-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)-2-azabicyclo[2.2.2]octane-2-carboxylate

Product 1

HCID 136333934tert-butyl (3S)-3-[6-(5-methyl-1H-pyrazol-4-yl)-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl]-2-azabicyclo[2.2.2]octane-2-carboxylateYield 76.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl (3S)-3-(6-Bromo-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)-2-azabicyclo[2.2.2]octane-2-carboxylate (190 mg), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (266 mg), sodium carbonate (78 mg), 1,2-dimethoxyethane (3.0 mL) and water (1.5 mL) were placed in a flask, and the atmosphere in the flask was purged with argon. [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane complex (1:1) (35 mg) was added, and the atmosphere in the flask was purged again with argon. The reaction system was stirred at 100° C. for 3 hr, and the mixture was extracted with ethyl acetate and dried over anhydrous sodium sulfate. Insoluble material was removed by filtration, and the extract was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the obtained pale-yellow solid was crystallized from methanol/ethyl acetate to give the title compound (146 mg) as a pale-yellow solid.

Workup

  1. customthe atmosphere in the flask was purged with argon
  2. addition[1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane complex (1:1) (35 mg) was added
  3. customthe atmosphere in the flask was purged again with argon
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialdried over anhydrous sodium sulfate
  6. customInsoluble material was removed by filtration
  7. concentrationthe extract was concentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  9. customthe obtained pale-yellow solid was crystallized from methanol/ethyl acetate

Sources & evidence

ORD record
ord-a1ae7c0e238b444da7361659989a862d
Source dataset
uspto-grants-2014_05
Patent number
US08722660B2

Reaction notes

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