Cesium carbonate → 5-Bromo-3-(1-cyclopropyl-1H-pyrazol-4-ylamino)-1-methylpyrazin-2(1H)-one

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Reaction Steps

A 100-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet was charged with 109b (378 mg, 3.07 mmol), 3,5-dibromo-1-methylpyrazin-2(1H)-one (906 mg, 3.38 mmol), cesium carbonate (3.00 g, 9.21 mmol), and 1,4-dioxane (45 mL). After bubbling nitrogen through the resulting suspension for 30 min, Xantphos (151 mg, 0.261 mmol) and tris(dibenzylidene-acetone)dipalladium(0) (141 mg, 0.154 mmol) were added, and the reaction mixture was heated at reflux for 3 h. After this time, the mixture was cooled to room temperature and diluted with ethyl acetate (150 mL) and water (30 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×45 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 0% to 10% methanol/methylene chloride) to afford a 28% yield (266 mg) of 109c as an off-white solid: mp 228-230° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.06 (s, 1H), 7.69 (s, 1H), 7.21 (s, 1H), 3.70 (m, 1H), 3.41 (s, 3H), 0.96 (m, 4H); MS (ESI+) m/z 310.0 (M+H).

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