1,2-Dimethoxyethane → 2,2-dimethyl-6-(1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

HRID 2363973Notes

Reaction equation

HRID 2363973 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([CH3:13])([CH3:12])[NH:5][C:4]=2[CH:3]=1.[NH:14]1[CH:18]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:16]=[N:15]1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[CH3:12][C:6]1([CH3:13])[NH:5][C:4]2[CH:3]=[C:2]([C:17]3[CH:18]=[N:14][NH:15][CH:16]=3)[S:10][C:9]=2[C:8](=[O:11])[NH:7]1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 667434256-bromo-2,2-dimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

Product 1

HCID 667438422,2-dimethyl-6-(1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneYield 26%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-bromo-2,2-dimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (0.125 g, 0.480 mmol), 4-pyrazoleboronic acid pinacol ester (0.279 g, 1.44 mmol), sodium carbonate (0.254 g, 2.40 mmol), 1,2-dimethoxyethane (2.4 mL) and water (1.2 mL) was purged with argon. Then, 1,1′-bis (diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (0.041 g, 0.050 mmol) was added to the mixture and the mixture was purged with argon again. The mixture was stirred at 120° C. for 4 h in a sealed tube. The mixture was poured into sat. aqueous sodium hydrogen carbonate (50 mL). Extraction with ethyl acetate/THF (3:1, 2×50 mL), drying over magnesium sulfate, filtration and concentration at reduced pressure were carried out. The residue was purified by column chromatography (Combiflash, 12 g silica gel, dichloromethane to 90:10 dichloromethane/methanol). The fractions containing the desired product were collected. Some amount of starting material was recovered, reacted and purified with the above conditions again. The fractions containing the desired product were combined and concentrated in vacuo. This residue was further purified by column chromatography (Combiflash, 12 g silica gel, ethyl acetate to 90:10 ethyl acetate/methanol), then triturated with dichloromethane. The precipitate was collected by filtration to afford the title compound (0.0308 g, 26%) as a yellow solid:

Workup

  1. customwas purged with argon
  2. customthe mixture was purged with argon again
  3. additionThe mixture was poured into sat. aqueous sodium hydrogen carbonate (50 mL)
  4. extractionExtraction with ethyl acetate/THF (3:1, 2×50 mL)
  5. dry with materialdrying over magnesium sulfate, filtration and concentration at reduced pressure
  6. customThe residue was purified by column chromatography (Combiflash, 12 g silica gel, dichloromethane to 90:10 dichloromethane/methanol)
  7. additionThe fractions containing the desired product
  8. customwere collected
  9. customSome amount of starting material was recovered
  10. customreacted
  11. custompurified with the above conditions again
  12. additionThe fractions containing the desired product
  13. concentrationconcentrated in vacuo
  14. customThis residue was further purified by column chromatography (Combiflash, 12 g silica gel, ethyl acetate to 90:10 ethyl acetate/methanol)
  15. customtriturated with dichloromethane
  16. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-a111eab197f645f19b2e33a953e7bd59
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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