Cesium carbonate → 1,2,2-trimethyl-6-(5-methyl-1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

HRID 2364029Notes

Reaction equation

HRID 2364029 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([CH3:13])([CH3:12])[N:5]([CH3:14])[C:4]=2[CH:3]=1.[CH3:15][C:16]1[C:20](B2OC(C)(C)C(C)(C)O2)=[CH:19][NH:18][N:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O.COCCOC>[CH3:14][N:5]1[C:4]2[CH:3]=[C:2]([C:20]3[CH:19]=[N:18][NH:17][C:16]=3[CH3:15])[S:10][C:9]=2[C:8](=[O:11])[NH:7][C:6]1([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 10796Cesium carbonate2×HCID 667439846-bromo-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneHCID 178434487HCID 178434487, compound2×

Product 1

HCID 667433211,2,2-trimethyl-6-(5-methyl-1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneYield 38.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

A mixture of 6-bromo-1,2,2-trimethyl-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (138 mg, 0.50 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (208 mg, 1.00 mmol), cesium carbonate (489 mg, 1.50 mmol), 1,2-dimethoxyethane (5 mL) and water (1 mL) was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (40.8 mg, 0.050 mmol) was added, and the mixture was purged with argon again. This mixture was refluxed for 18 h. After cooling to room temperature, 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.208 g, 1.00 mmol), Cs2CO3 (0.489 g, 1.50 mmol), 1,2-dimethoxyethane (5 mL) and water (1 mL) were added. The mixture was purged with argon. Then, 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (0.041 g, 0.050 mmol) was added, and the mixture was purged with argon again. The mixture was refluxed for 6 h. Then, the mixture was poured into saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (100 mL), and the extract was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. This residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc). The obtained yellow solid was triturated with EtOAc and collected by filtration to afford the title compound (52.7 mg, 38%) as a pale yellow solid:

Workup

  1. customwas purged with argon
  2. customthe mixture was purged with argon again
  3. temperatureThis mixture was refluxed for 18 h
  4. customThe mixture was purged with argon
  5. customthe mixture was purged with argon again
  6. temperatureThe mixture was refluxed for 6 h
  7. additionThen, the mixture was poured into saturated aqueous NaHCO3 (100 mL)
  8. extractionextracted with EtOAc (100 mL)
  9. washthe extract was washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThis residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc)
  14. customThe obtained yellow solid was triturated with EtOAc
  15. filtrationcollected by filtration

Sources & evidence

ORD record
ord-866236ab5a6c416bbed133926ff0d4d1
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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