Cesium carbonate → ethyl 5-((2R,4S)-2-(3-cyano-5-fluorophenyl)-4-fluoropyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A N2 purged flask was charged with ethyl 5-bromopyrazolo[1,5-a]pyridine-3-carboxylate (36 mg, 0.13 mmol), tris(dibenzylideneacetone)dipalladium(0) (2.5 mg, 2 μmol), xantphos (6 mg, 8 μmol), cesium carbonate (61 mg, 0.19 mmol), 1,4-dioxane (0.5 mL) and 3-fluoro-5-((2R,4S)-4-fluoropyrrolidin-2-yl)benzonitrile (I-15) (28 mg, 0.13 mmol). The contents were heated to 140° C. for 25 minutes under microwave irradiation. Upon cooling to room temperature the reaction was partitioned with EtOAc and water. The organic layer was washed with water, brine, dried over magnesium sulfate, filtered and reduced to dryness. The crude product was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant to yield ethyl 5-((2R,4S)-2-(3-cyano-5-fluorophenyl)-4-fluoropyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylate (X-7). 1H NMR (400 MHz, CDCl3) δ 8.22 (s, 1 H), 8.21 (d, J=7.6 Hz, 1 H), 7.39 (s, 1 H), 7.31-7.27 (m, 1 H), 7.26-7.21 (m, 1 H), 6.94 (d, J=2.4 Hz, 1 H), 6.24 (dd, J=2.8, 7.6 Hz, 1 H), 5.40 (d, J=52.4 Hz, 1 H), 5.07 (dd, J=7.2, 9.6 Hz, 1 H), 4.35-4.26 (m, 2 H), 4.23-4.08 (m, 1 H), 4.05-3.93 (m, 1 H), 2.97-2.85 (m, 1 H), 2.17-1.99 (m, 1 H), 1.35 (t, J=7.2 Hz, 3 H). MS m/z 397.1 (M+1)+.

Provenance & Evidence