Cesium carbonate → 3-Chloro-2-{7-fluoro-4-[6-(1-hydroxyethyl)-pyrimidin-4-ylamino]-pyrazolo[4,3-c]pyridin-2-yl}-benzonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-(4-bromo-7-fluoropyrazolo[4,3-c]pyridin-2-yl)-3-chlorobenzonitrile (211 mg, 0.61 mmol), 1-(6-aminopyrimidin-4-yl)-ethanol (92 mg, 0.66 mmol), Pd2(dba)3 (14 mg, 0.015 mmol), Xantphos (35 mg, 0.06 mmol) and cesium carbonate (391 mg, 1.2 mmol) in dioxane (4.0 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 150° C. in the microwave for 30 minutes. The resultant mixture was partitioned between ethyl acetate and water. The layers were separated and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (ethyl acetate) to afford the title compound as a beige solid (61 mg, 25% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.84 (s, 1H), 9.47 (d, J=2.5 Hz, 1H), 8.72 (d, J=1.2 Hz, 1H), 8.59 (s, 1H), 8.24-8.21 (m, 2H), 8.02 (d, J=3.5 Hz, 1H), 7.90 (t, J=8.1 Hz, 1H), 5.54 (d, J=4.6 Hz, 1H), 4.70-4.63 (m, 1H), 1.39 (d, J=6.6 Hz, 3H). LCMS (Method B): RT=2.92 min, m/z: 410 [M+H+].

Provenance & Evidence