Hydrochloric Acid → 2-methyl-6-(5-methyl-1H-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

HRID 2364035Notes

Reaction equation

HRID 2364035 reaction equation
[CH3:1][C:2]1([CH3:18])[NH:7][C:6]2[CH:8]=[C:9]([C:11]3[CH:12]=[N:13][NH:14][C:15]=3[CH3:16])[S:10][C:5]=2[C:4](=[O:17])[NH:3]1.Cl.C([O-])(O)=O.[Na+].[F:25][C:26]([F:32])([F:31])CC(=O)C.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[O-]S([O-])(=O)=O.[Mg+2]>CCCCCCC.CCOC(C)=O.CC(N(C)C)=O.CO>[CH3:1][C:2]1([CH2:18][C:26]([F:32])([F:31])[F:25])[NH:7][C:6]2[CH:8]=[C:9]([C:11]3[CH:12]=[N:13][NH:14][C:15]=3[CH3:16])[S:10][C:5]=2[C:4](=[O:17])[NH:3]1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium Bicarbonate2×HCID 5390014,4,4-Trifluorobutan-2-oneHCID 66743505Cdc7-IN-15

Product 1

HCID 667438482-methyl-6-(5-methyl-1H-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneYield 30%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 2,2-dimethyl-6-(5-methyl-1H-pyrazol-4-yl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one, 1 M HCl (1.2 mL, 1.2 mmol) and MeOH (4 mL) was stirred at 50° C. for 2 h. Then, the reaction mixture was poured into excess saturated aqueous NaHCO3 and extracted with EtOAc, and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was mixed with 4,4,4-trifluorobutan-2-one (0.433 g, 3.43 mmol), CSA (7.97 mg, 0.034 mmol), MgSO4 (0.041 g, 0.343 mmol) and DMA (1 mL). The mixture was microwave-irradiated at 140° C. for 1 h. 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 (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc then to 90:10 EtOAc/MeOH). The obtained oil was purified again by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc) to give yellow oil. This oil was dissolved with small amount of EtOAc and poured into heptane (100 mL) with stirring. After 5 min, the precipitate was collected by filtration to afford the title compound (33.5 mg, 30%) as a yellow solid:

Workup

  1. extractionextracted with EtOAc
  2. dry with materialthe extract was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe mixture was microwave-irradiated at 140° C. for 1 h
  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 (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc
  11. customThe obtained oil was purified again by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc)
  12. customto give yellow oil
  13. stirringwith stirring
  14. waitAfter 5 min
  15. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-2cdba64fde0548bcad2b6998549b36e4
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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