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) (42 mg, 0.12 mmol) in DMF (1 mL) was added DIEA (64 μL, 0.36 mmol) and HATU (51 mg, 0.13 mmol). The reaction was stirred at room temperature for 10 minutes, then a solution of NH4Cl (20 mg, 0.36 mmol) in NH4OH (100 μL) was added and stirred for 3 hours. The crude reaction mixture was diluted with EtOAc and washed with water, brine, dried over magnesium sulfate, filtered and reduced to dryness. Purification by column chromatography on silica gel with DCM/MeOH gradient as eluant gave 5-((2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (X-5). 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J=7.6 Hz, 1 H), 7.96 (s, 1H), 7.32 (td, J=6.0, 7.8 Hz, 1H), 7.20 (d, J=2.4 Hz, 1 H), 7.06 (d, J=7.6 Hz, 1 H), 6.99-6.90 (m, 2 H), 6.21 (dd, J=2.8, 7.6 Hz, 1 H), 5.40 (bs, 2 H), 5.38 (d, J=52.4 Hz, 1 H), 5.05 (dd, J=7.2, 9.2 Hz, 1 H), 4.18-3.92 (m, 2 H), 2.92-2.80 (m, 1 H), 2.11 (dddd, J=3.6, 9.2, 13.2, 40.0 Hz, 1 H). MS m/z 343.1 (M+1)+.

1. stirringstirred for 3 hours
2. customThe crude reaction mixture
3. washwashed with water, brine
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. customPurification by column chromatography on silica gel with DCM/MeOH gradient as eluant