反应详情

To a solution of 5-((2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylic acid (X-3) (50 mg, 0.15 mmol) and DIEA (0.052 mL, 0.30 mmol) in THF (0.75 mL) under N2 was added DPPA (0.035 mL, 0.17 mmol) and the reaction was stirred overnight at room temperature. NH4Cl (42 mg, 0.73 mmol) and NH4OH were added to the reaction and the mixture was heated to 65° C. overnight. Upon cooling to room temperature the reaction was concentrated, taken up in MeOH and filtered. The filtrate was purified by preparative LCMS and lyophilized to give 1-(5-((2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)urea (X-23). 1H NMR (400 MHz, MeOD) δ 8.19-8.08 (m, 1 H), 7.83-7.67 (m, 1 H), 7.35 (dd, J=7.8, 14.0 Hz, 1 H), 7.16 (d, J=7.6 Hz, 1H), 7.11-7.01 (m, 1 H), 6.97 (t, J=8.5 Hz, 1 H), 6.44 (bd, J=5.7 Hz, 1 H), 6.26 (bs, 1 H), 5.40 (d, J=52.9 Hz, 1 H), 5.12-4.99 (m, 1 H), 4.16 (dd, J=11.4, 35.7 Hz, 1 H), 3.87 (dd, J=12.0, 23.4 Hz, 1 H), 2.93-2.77 (m, 1 H), 2.24-2.04 (m, 1 H). MS m/z 358.1 (M+1)+.

1. temperaturethe mixture was heated to 65° C. overnight
2. temperatureUpon cooling to room temperature the reaction
3. concentrationwas concentrated
4. filtrationfiltered
5. customThe filtrate was purified by preparative LCMS