Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → 7-bromo-2-methyl-6-(1H-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-one

HRID 2364048Notes

Reaction equation

HRID 2364048 reaction equation
[NH2:1][C:2]1[C:6]([Br:7])=[C:5]([C:8]2[CH:9]=[N:10][NH:11][CH:12]=2)[S:4][C:3]=1[C:13]([NH2:15])=[O:14].[F:16][C:17]([F:23])([F:22])[CH2:18][C:19](=O)[CH3:20].CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[O-]S([O-])(=O)=O.[Mg+2].C([O-])(O)=O.[Na+]>CC(N(C)C)=O>[Br:7][C:6]1[C:2]2[NH:1][C:19]([CH3:20])([CH2:18][C:17]([F:23])([F:22])[F:16])[NH:15][C:13](=[O:14])[C:3]=2[S:4][C:5]=1[C:8]1[CH:9]=[N:10][NH:11][CH:12]=1

Participants

7

Reactant 5

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 24083Sulfuric acid magnesium salt (1:1)HCID 516892Sodium BicarbonateHCID 5390014,4,4-Trifluorobutan-2-oneHCID 667431873-amino-4-bromo-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide

Product 1

HCID 667440707-bromo-2-methyl-6-(1H-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-oneYield 24%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A mixture of 3-amino-4-bromo-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide (90 mg, 0.313 mmol), 4,4,4-trifluorobutan-2-one (395 mg, 3.13 mmol), CSA (7.28 mg, 0.031 mmol), MgSO4 (37.7 mg, 0.313 mmol) and DMA (2 mL) was microwave-irradiated at 150° C. for 3 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). The obtained solid was triturated with EtOAc, and the precipitate was collected by filtration to afford the title compound (29.2 mg, 24%) as a white solid:

Workup

  1. customwas microwave-irradiated at 150° C. for 3 h
  2. extractionextracted with EtOAc
  3. dry with materialthe extract was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc)
  7. customThe obtained solid was triturated with EtOAc
  8. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-059b5d5a60784be2a8789d71554fd99a
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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