(S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one → (S)-3-(3-(3-fluoro-4-(1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one

HRID 539058Notes

Reaction equation

HRID 539058 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:21]2[CH:22]=[N:23][N:24]3[CH:29]=[CH:28][C:27]([N:30]4[C@@H:34]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[CH2:33][O:32][C:31]4=[O:41])=[N:26][C:25]=23)[CH:5]=[CH:6][C:7]=1[C:8]1[N:12]=[CH:11][N:10](COCC[Si](C)(C)C)[N:9]=1>C(O)(C(F)(F)F)=O>[F:1][C:2]1[CH:3]=[C:4]([C:21]2[CH:22]=[N:23][N:24]3[CH:29]=[CH:28][C:27]([N:30]4[C@@H:34]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[CH2:33][O:32][C:31]4=[O:41])=[N:26][C:25]=23)[CH:5]=[CH:6][C:7]=1[C:8]1[N:12]=[CH:11][NH:10][N:9]=1

Participants

3

Reactant 1

HCID 67034121(S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one

Product 1

HCID 178519139(S)-3-(3-(3-fluoro-4-(1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-oneYield 25.4%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To the solid (S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one (0.30 g, 0.525 mmol) was added TFA (10 mL) and the reaction stirred for 2 hours at ambient temperature. The reaction was concentrated in vacuo and the material was slurried in water (5 mL) with acetonitrile/methanol (10 mL, 1:1) and stirred for 3 hours. The slurry was filtered and the solids were dried in vacuo. The solids were then taken up in water and the water layer was basified with a solution of saturated NaHCO3, and the solids were filtered. The solids were again slurried in water, then filtered and concentrated. The residue was slurried in water/acetonitrile/methanol (30 mL total) and nitrogen was bubbled through the solution to drive complete deprotection. The slurry was filtered and the isolated solids were taken up in acetonitrile (3 mL) and heated to reflux, then cooled. The mixture was filtered and concentrated in vacuo to yield (S)-3-(3-(3-fluoro-4-(1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-phenyloxazolidin-2-one (0.0589 g, 0.133 mmol, 25.4% yield) as the free base. LCMS (APCI+) m/z 442 [M+H]+.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. stirringstirred for 3 hours
  3. filtrationThe slurry was filtered
  4. customthe solids were dried in vacuo
  5. filtrationthe solids were filtered
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customnitrogen was bubbled through the solution
  9. filtrationThe slurry was filtered
  10. temperatureheated
  11. temperatureto reflux
  12. temperaturecooled
  13. filtrationThe mixture was filtered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d46cccf67992434fb906ad186c449390
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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