Trifluoroacetic acid → HCID 50995200, compound

HRID 538983Notes

Reaction equation

HRID 538983 reaction equation
[CH3:1][C@H:2]1[CH2:6][O:5][C:4](=[O:7])[NH:3]1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].CC1C=CC(S(O[C:29]2[CH:34]=[CH:33][N:32]3[N:35]=[CH:36][C:37]([C:38]4[CH:43]=[CH:42][C:41]([C:44]5[N:45](COCC[Si](C)(C)C)[CH:46]=[CH:47][N:48]=5)=[CH:40][CH:39]=4)=[C:31]3[N:30]=2)(=O)=O)=CC=1.[NH4+].[Cl-].FC(F)(F)C(O)=O>CN(C=O)C.ClCCl>[NH:45]1[CH:46]=[CH:47][N:48]=[C:44]1[C:41]1[CH:42]=[CH:43][C:38]([C:37]2[CH:36]=[N:35][N:32]3[CH:33]=[CH:34][C:29]([N:3]4[C@@H:2]([CH3:1])[CH2:6][O:5][C:4]4=[O:7])=[N:30][C:31]=23)=[CH:39][CH:40]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 8063308(S)-4-Methyloxazolidin-2-oneHCID 86667821HCID 86667821, compound

Product 1

HCID 50995200HCID 50995200, compoundYield 8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of (S)-4-methyloxazolidin-2-one (9.0 mg, 0.089 mmol) in dry DMF (0.5 mL) was cooled to 0° C. Sodium hexamethyldisilazide (0.089 mL, 0.089 mmol) was added and the resulting yellow solution stirred for 10 minutes before addition of a solution of 3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl 4-methylbenzenesulfonate (20.0 mg, 0.0356 mmol) in DMF (0.5 mL). The mixture was then brought to ambient temperature prior to heating at 80° C. for 1 hour. The cooled reaction mixture was poured into saturated aqueous NH4Cl and extracted with EtOAc. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. Purification of the crude material by column chromatography, eluting with 1-2% MeOH/dichloromethane afforded the protected intermediate which was taken up in dichloromethane (1 mL). Trifluoroacetic acid (3 mL) was added and the mixture stirred at ambient temperature for 12 hours. The reaction mixture was concentrated, washed with saturated aqueous NaHCO3, extracted into ethyl acetate, dried over sodium sulfate, filtered and concentrated. Purification of the crude material by column chromatography, eluting with 2-4% MeOH/dichloromethane, afforded (S)-3-(3-(4-(1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-methyloxazolidin-2-one as a light yellow solid (1 mg, 8%). LCMS (APCI+) m/z 361 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (d, J=7.8 Hz, 1H), 8.54 (s, 1H), 8.17 (d, J=8.6 Hz, 2H), 7.97 (d, J=7.8 Hz, 1H), 7.91 (d, J=8.6 Hz, 2H), 7.14 (s, 2H), 5.06-5.13 (m, 1H), 4.65 (t, J=8.2 Hz, 1H), 4.21-4.24 (m, 1H), 1.66 (d, J=6.2 Hz, 3H).

Workup

  1. customwas then brought to ambient temperature
  2. customThe cooled reaction mixture
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the crude material by column chromatography
  8. washeluting with 1-2% MeOH/dichloromethane
  9. customafforded the protected intermediate which
  10. concentrationThe reaction mixture was concentrated
  11. washwashed with saturated aqueous NaHCO3
  12. extractionextracted into ethyl acetate
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customPurification of the crude material by column chromatography
  17. washeluting with 2-4% MeOH/dichloromethane

Sources & evidence

ORD record
ord-9d8d91f35c934cac891c0fe039f78e2f
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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