Cesium carbonate → 7-[(2-chloro-5-fluoropyridin-4-yl)amino]-2-methyl-4-(4-propan-2-ylpiperazin-1-yl)-3H-isoindol-1-one

Participants

Reaction Conditions

Reaction Steps

Cesium carbonate (960 mg, 2.95 mmol) was added to 7-amino-2-methyl-4-(4-propan-2-ylpiperazin-1-yl)-3H-isoindol-1-one (425 mg, 1.47 mmol), 2-chloro-5-fluoro-4-iodopyridine (379 mg, 1.47 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (51.2 mg, 0.09 mmol) and palladium(II) acetate (13.23 mg, 0.06 mmol) in dioxane (15 mL) under an atmosphere of nitrogen. The resulting suspension was heated at 80° C. for 18 hours and then allowed to cool to room temperature. The mixture was filtered and then filtrate evaporated. The residue was dissolved in EtOAc (150 mL), and the solution washed sequentially with a saturated solution of NaHCO3 (75 mL), water (75 mL), and finally with a saturated solution of NaCl (75 mL). The organic layer was dried over MgSO4 and then evaporated. The residue was triturated with Et2O and dried to afford 7-[(2-chloro-5-fluoropyridin-4-yl)amino]-2-methyl-4-(4-propan-2-ylpiperazin-1-yl)-3H-isoindol-1-one (432 mg, 70% yield); 1H NMR spectrum (300.132 MHz, CDCl3): δ 1.11 (6H, d), 2.70 (4H, m), 2.76 (1H, m), 3.07 (4H, m), 3.18 (3H, s), 4.37 (2H, s), 7.14 (1H, d), 7.33-7.41 (2H, m), 8.06 (1H, d), 9.40 (1H, d); Mass spectrum: m/z (ESI+) (M+H)+ =418.31.

Provenance & Evidence