Benzyl Alcohol → benzyl (5-((2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)carbamate

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) (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. Benzyl alcohol (0.025 mL, 0.24 mmol) was added to the reaction and the mixture was heated to 65° C. for 3 days. Upon cooling to room temperature the reaction was partitioned with EtOAc and aqueous saturated NaHCO3. The organics were dried over Na2SO4, filtered, and concentrated. The crude product was purified by column chromatography on silica gel with an EtOAc/hexane gradient as eluant to yield benzyl (5-((2R,4S)-4-fluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridin-3-yl)carbamate (X-21). 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J=8.2 Hz, 1 H), 7.78 (s, 1 H), 7.52-7.25 (m, 6 H), 7.01 (d, J=7.6 Hz, 1 H), 6.98-6.84 (m, 2 H), 6.13 (d, J=6.9 Hz, 2 H), 5.36 (d, J=52.9 Hz, 1 H), 5.20 (s, 2 H), 5.03-4.86 (m, 1 H), 4.17-3.93 (m, 1 H), 3.93-3.72 (m, 1 H), 2.92-2.73 (m, 1 H), 2.16-1.97 (m, 1 H). MS m/z 449.1 (M+1)+.

Provenance & Evidence