Ammonium Chloride → 5-((2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

Participants

Reaction Steps

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)+.

Provenance & Evidence