Trifluoroacetic acid → HCID 50995200, compound

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence