Cesium carbonate → Cyclopropanecarboxylic acid {6-[2-(2,6-dichloro-4-cyanophenyl)-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-amide

Participants

Reaction Steps

A suspension of 3,5-dichloro-4-(4-chloropyrazolo[4,3-c]pyridin-2-yl)benzonitrile (132 mg, 0.41 mmol), cyclopropanecarboxylic acid (6-amino-pyrimidin-4-yl)-amide (80 mg, 0.45 mmol), Pd2(dba)3 (19 mg, 0.02 mmol), Xantphos (24 mg, 0.04 mmol) and cesium carbonate (266 mg, 0.82 mmol) in dioxane (2 mL) was sealed in a microwave vial after degassing with nitrogen. The mixture was irradiated at 150° C. for 30 minutes in the microwave and then cooled to room temperature. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated and washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane), then by HPLC (gradient: 5 to 98% acetonitrile in water with 0.1% ammonium hydroxide), to afford the title compound as an off-white solid (49 mg, 26% yield). 1H NMR (400 MHz, DMSO-d6+d-TFA): δ 9.47 (s, 1H), 8.79 (d, 1H), 8.47 (s, 2H), 8.09 (d, J=0.9 Hz, 1H), 7.99 (d, J=7.6 Hz, 1H), 7.55 (dd, J=7.6, 0.9 Hz, 1H), 2.10-2.02 (m, 1H), 0.93-0.90 (m, 4H). LCMS (Method B): RT=3.17 min, m/z: 465 [M+H+].

Provenance & Evidence