反应详情

温度

0 °C

A solution of morpholine-4-carboxylic acid 1-[2-(4-fluorophenyl)acetyl]-2-(2-phenoxypyrimidine-4-carbonyl)-pyrazolidin-4-yl ester, 42, (154 mg, 0.287 mmol) in dimethylformamide (3 mL) is added dropwise to a −10° C. suspension of sodium hydride (16.4 mg of a 60% dispersion in mineral oil, 0.410 mmol) in tetrahydrofuran (3 mL). After 1 hour at −10° C., the reaction was warmed to 0° C. for 2 hours. The orange-colored solution is then quenched by slowly adding saturated NH4Cl (400 μL). The cooling bath is removed, and the solution allowed to warm to room temperature. The reaction mixture is concentrated in vacuo and the resulting residue is dissolved in THF (25 mL) and filtered through a pad of Celite. The filtrate is concentrated in vacuo and the residue purified by Prep HPLC to afford 47 mg (32% yield) of the desired product as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.46 (d, J=4.9 Hz, 1H), 7.47–7.18 (m, 9H), 7.08 (t, J=8.7 Hz, 2H), 6.89 (d, J=4.9 Hz, 1H), 5.66 (m, 1H), 4.16 (m, 2H), 4.02 (d, J=12.9Hz, 1H), 3.87 (dd, J=12.9, 5.1 Hz, 1H), 3.79–3.30 (m, 8H); HRMS m/z calcd for C27H25FN5O5 (MH+) 518.1840, found 518.1815.

1. customThe orange-colored solution is then quenched by slowly adding saturated NH4Cl (400 μL)
2. customThe cooling bath is removed
3. temperatureto warm to room temperature
4. concentrationThe reaction mixture is concentrated in vacuo
5. dissolutionthe resulting residue is dissolved in THF (25 mL)
6. filtrationfiltered through a pad of Celite
7. concentrationThe filtrate is concentrated in vacuo
8. customthe residue purified by Prep HPLC