Cesium carbonate → 6-Chloro-2-methyl-2,3-dihydropyridazin-3-one

関与物質

反応手順

A mixture of potassium trifluoro(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)borate (60 mg, 0.20 mmol), 6-chloro-2,4-dimethylpyridazin-3(2H)-one (made according to US2012/108578 A1, 40 mg, 0.24 mmol), [1,1′-bis(diphenylphosphino) ferrocene]dichloro-palladium(II) (14 mg, 0.02 mmol) and cesium carbonate (163 mg, 0.5 mmol) in THF (0.8 mL) and H2O (0.2 mL) was stirred at reflux for 15 h. The mixture was cooled to ambient temperature, diluted with EtOAc (5 mL), washed with sodium bicarbonate (2 mL) and brine (2 mL), dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase chromatography (Waters Sunfire C18 OBD 5˜80% methanol in water with 0.1% NH3. H2O modifer) to give the title compound as a white solid LC/MS m/z=378.1 [M+H]+; 1H NMR (400 MHz, MeOD) δ 8.53 (s, 1 H), 8.09 (s, 1 H), 7.65 (s, 1 H), 7.41 (dd, 1 H), 7.04 (d, 1 H), 4.66-4.51 (m, 1 H), 4.25 (dd, 1 H), 3.71 (s, 3 H), 2.51 (s, 3H), 2.18 (s, 3 H), 2.11-2.02 (m, 1 H), 1.92 (s, 3 H), 1.85-1.73 (m, 1 H), 1.22-1.13 (m, 1 H), 1.09-1.00 (m, 1 H).

情報源と証拠