Acetone → 7-bromo-2,2-dimethyl-6-(1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

HRID 2364030Notes

Reaction equation

HRID 2364030 reaction equation
[CH3:1][C:2]1([CH3:17])[NH:7][C:6]2[CH:8]=[C:9]([C:11]3[CH:12]=[N:13][NH:14][CH:15]=3)[S:10][C:5]=2[C:4](=[O:16])[NH:3]1.[Br:18]Br.C([O-])(O)=O.[Na+].CC(C)=O.CC1C=CC(S(O)(=O)=O)=CC=1.[O-]S([O-])(=O)=O.[Mg+2]>C(O)(=O)C.CN(C=O)C>[Br:18][C:8]1[C:6]2[NH:7][C:2]([CH3:17])([CH3:1])[NH:3][C:4](=[O:16])[C:5]=2[S:10][C:9]=1[C:11]1[CH:15]=[N:14][NH:13][CH:12]=1

Participants

9

Reactant 6

HCID 180AcetoneHCID 6101p-Toluenesulfonic acidHCID 24083Sulfuric acid magnesium salt (1:1)HCID 24408BromineHCID 516892Sodium Bicarbonate2×HCID 667438422,2-dimethyl-6-(1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

Product 1

HCID 667432407-bromo-2,2-dimethyl-6-(1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneYield 30.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2,2-dimethyl-6-(1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one (248 mg, 1.00 mmol) in acetic acid (5 mL) was added slowly bromine (0.077 mL, 1.50 mmol) with vigorous stirring. After 3 min, the mixture was poured into saturated aqueous NaHCO3 and extracted with EtOAc, and the extract was dried over MgSO4, filtered and concentrated under reduced pressure to give a yellow solid. This residue was mixed with acetone (5.0 mL, 68.1 mmol), PTSA (9.5 mg, 0.050 mmol), MgSO4 (120 mg, 1.00 mmol) and DMF (1 mL). This mixture was stirred at 60° C. for 1 h. Then, the mixture was poured into saturated aqueous NaHCO3 and extracted with EtOAc, and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, hexane to EtOAc) to give a pale yellow solid (100 mg). This solid was triturated with EtOAc and collected by filtration to afford the title compound (69.9 mg, 21%) as a pale yellow solid:

Workup

  1. extractionextracted with EtOAc
  2. dry with materialthe extract was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give a yellow solid
  6. extractionextracted with EtOAc
  7. dry with materialthe extract was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography (silica gel, hexane to EtOAc)

Sources & evidence

ORD record
ord-11a19a1bad274f2987b4853765e59626
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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