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

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A N2 purged flask was charged with ethyl 5-bromopyrazolo[1,5-a]pyridine-3-carboxylate (30 mg, 0.11 mmol), palladium acetate (1.0 mg, 5 μmol), RuPhos (5 mg, 10 μmol), cesium carbonate (65 mg, 0.20 mmol), tBuOH (0.5 mL) and (3S,5R)-5-(3-fluorophenyl)pyrrolidine-3-carbonitrile 2,2,2-trifluoroacetate (I-31) (30 mg, 0.10 mmol). The contents were heated to 120° C. overnight in an oil bath. Upon cooling to room temperature the reaction was filtered through celite and concentrated. The crude product was purified by column chromatography on silica gel with an EtOAc/hexane gradient as eluant to yield ethyl 5-((2R,4S)-4-cyano-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylate (X-19). 1H NMR (400 MHz, CDCl3) δ 8.25 (s, 1 H), 8.22 (d, J=7.6 Hz, 1 H), 7.40-7.32 (m, 1 H), 7.07-6.96 (m, 3 H), 6.88 (d, J=9.4 Hz, 1 H), 6.24 (dd, J=2.7, 7.6 Hz, 1 H), 5.10 (dd, J=2.5, 8.0 Hz, 1 H), 4.39-4.29 (m, 2 H), 4.23-4.14 (m, 1 H), 3.95-3.78 (m, 1 H), 3.42-3.29 (m, 1 H), 2.92-2.78 (m, 1 H), 2.50-2.39 (m, 1 H), 1.36 (t, J=7.1 Hz, 3 H). MS m/z 379.1 (M+1)+. Further elution with MeOH/DCM gradient afforded ethyl 5-((2R,4S)-4-carbamoyl-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxylate (X-20). MS m/z 397.1 (M+1)+.

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