Cesium carbonate → tert-Butyl 2-(4-(6-Bromo-4-methyl-3-oxo-3,4-dihydropyrazin-2-ylamino)phenyl)-4-methyl-3-oxopiperazine-1-carboxylate

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Reaction Steps

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet and reflux condenser was charged with tert-butyl 2-(4-aminophenyl)-4-methyl-3-oxopiperazine-1-carboxylate 102j (880 mg, 2.88 mmol), 3,5-dibromo-1-methylpyrazin-2(1H)-one (770 mg, 2.88 mmol), cesium carbonate (2.06 g, 6.34 mmol) and 1,4-dioxane (20 mL). After bubbling nitrogen through the resulting solution for 30 minutes, Xantphos (166 mg, 0.288 mmol) and tris(dibenzylidene acetone)dipalladium(0) (47 mg, 0.144 mmol) were added and the reaction mixture was heated at reflux for 18 h. After this time the reaction was cooled to room temperature, partitioned between ethyl acetate (50 mL) and water (50 mL), and filtered, and the filter cake was washed with ethyl acetate (2×25 mL). The organic layer was separated, washed with brine (50 mL) and dried over magnesium sulfate. The drying agent was removed by filtration and the filtrate concentrated under reduced pressure. The residue was purified by column chromatography to afford 102k (850 mg, 60%) as an orange foam: 1H NMR (300 MHz, CDCl3) δ 7.28 (s, 1H), 7.16 (d, 2H, J=8.4 Hz), 6.65 (d, 2H, J=8.4 Hz), 5.65 (s, 1H), 4.02 (m, 1H), 3.51 (m, 1H), 3.30 (m, 3H), 3.05 (s, 3H), 1.47 (s, 9H), MS (ESI+) m/z 492.1 (M+H).

Provenance & Evidence