Trifluoroacetic acid → (S)-3-(3-(4-(1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one

HRID 538980Notes

Reaction equation

HRID 538980 reaction equation
[CH:1]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[N:5]1[C:10]1[CH:15]=[CH:14][N:13]2[N:16]=[CH:17][C:18]([C:19]3[CH:24]=[CH:23][C:22]([C:25]4[N:26](COCC[Si](C)(C)C)[CH:27]=[CH:28][N:29]=4)=[CH:21][CH:20]=3)=[C:12]2[N:11]=1)([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[NH:26]1[CH:27]=[CH:28][N:29]=[C:25]1[C:22]1[CH:23]=[CH:24][C:19]([C:18]2[CH:17]=[N:16][N:13]3[CH:14]=[CH:15][C:10]([N:5]4[C@@H:4]([CH:1]([CH3:2])[CH3:3])[CH2:8][O:7][C:6]4=[O:9])=[N:11][C:12]=23)=[CH:20][CH:21]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67034475(S)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one

Product 1

HCID 50997719(S)-3-(3-(4-(1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-oneYield 61.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)oxazolidin-2-one (2.09 g, 4.03 mmol) was dissolved in dichloromethane (20 mL) and trifluoroacetic acid (25 mL) was added and the mixture allowed to stir at ambient temperature for 12 hours. The reaction mixture was concentrated and the residue partitioned between saturated aqueous NaHCO3 (50 mL) and EtOAc (100 mL). The aqueous layer was washed with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated to give a light yellow solid. Purification of the crude material by column chromatography, eluting with a gradient of 0-4% (9:1 MeOH/NH4OH)/EtOAc, provided (S)-3-(3-(4-(1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one as a yellow solid (961.3 mg, 61%). LCMS (APCI+) m/z 389 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J=7.8 Hz, 1H), 8.39 (s, 1H), 8.04 (d, J=8.6 Hz, 2H), 8.03 (d, J=7.8 Hz, 1H), 7.89 (d, J=8.6 Hz, 2H), 7.19 (s, 2H), 4.95-4.91 (m, 1H), 4.36-4.45 (m, 2H), 2.83-2.91 (m, 1H), 1.04 (d, J=7.0 Hz, 3H), 0.92 (d, J=7.0 Hz, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue partitioned between saturated aqueous NaHCO3 (50 mL) and EtOAc (100 mL)
  3. washThe aqueous layer was washed with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a light yellow solid
  9. customPurification of the crude material by column chromatography
  10. washeluting with a gradient of 0-4% (9:1 MeOH/NH4OH)/EtOAc

Sources & evidence

ORD record
ord-7c57d8acebf641a395159f52228e7352
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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