Cesium carbonate → 5-Bromo-3-(5-(3-hydroxyazetidin-1-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-one

Participants

Reaction Steps

A 100-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet was charged with 120b (270 mg, 1.64 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (435 mg, 1.64 mmol), cesium carbonate (1.18 g, 3.61 mmol), and 1,4-dioxane (20 mL). After bubbling nitrogen through the resulting suspension for 30 min, Xantphos (142 mg, 0.246 mmol) and tris(dibenzylidene-acetone)dipalladium(0) (150 mg, 0.164 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 filtered, and the filter cake was washed with methylene chloride (2×20 mL). The filtrates were combined and concentrated under reduced pressure, and the resulting residue was purified by column chromatography to afford a 40% yield (217 mg) of 120c as a yellow solid: 210° C. dec; 1H NMR (500 MHz, DMSO-d6) δ 8.50 (d, 1H, J=4.0 Hz), 8.44 (s, 1H), 7.54 (d, 1H, J=5.0 Hz), 7.42 (d, 1H, J=5.0 Hz), 7.20 (d, 1H, J=14.5 Hz), 6.89 (dd, 1H, J=14.5, 4.0 Hz), 5.59 (d, 1H, J=11.0 Hz), 4.54 (m, 1H), 4.05 (dd, 2H, J=13.0, 11.0 Hz), 3.50-3.44 (m, 5H); MS (APCI+) m/z 351.6 (M+H).

Provenance & Evidence