Cesium carbonate → 8-[(2-Chloro-5-fluoropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one

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Reaction Conditions

Reaction Steps

8-amino-2-methyl-3,4-dihydroisoquinolin-1-one (1.369 g, 7.77 mmol), cesium carbonate (5.06 g, 15.54 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.270 g, 0.47 mmol), palladium(II) acetate (0.070 g, 0.31 mmol) were added in order to a mixture of 2-chloro-5-fluoro-4-iodopyridine (2.000 g, 7.77 mmol) in dioxane (150 mL) at 20° C. under an atmosphere of nitrogen. The resulting suspension was heated at 80° C. for 4 hours and then left to stand at room temperature overnight. The mixture was filtered through Celite and the residue washed with CH2Cl2 (20 mL). The filtrate was evaporated and the residue dissolved in CH2Cl2 (100 mL) and then washed sequentially with water (2×150 mL) and a saturated solution of NaCl (100 mL). The organic layer was dried over Na2SO4 and then evaporated to leave a solid. The solid was triturated with Et2O and then dried under vacuum to afford 8-[(2-chloro-5-fluoropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one (2.117 g, 89% yield); 1H NMR spectrum (300 MHz, DMSO): δ 2.97 (2H, t), 3.06 (3H, s), 3.57 (2H, t), 6.97 (1H, dd), 7.42 (1H, d), 7.47-7.49 (2H, m), 8.26 (1H, d), 11.66 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+ =306.39 and 308.36.

Provenance & Evidence