Cesium carbonate → 2-[(2,5-dichloropyridin-4-yl)amino]-6-fluoro-N-methylbenzamide

Participants

Reaction Conditions

Reaction Steps

A mixture of palladium(II) acetate (53.4 mg, 0.24 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (206 mg, 0.36 mmol), cesium carbonate (3875 mg, 11.89 mmol), 2-amino-6-fluoro-N-methylbenzamide (1000 mg, 5.95 mmol) and 2,5-dichloro-4-iodopyridine (1710 mg, 6.24 mmol) in dioxane (50 mL) under an atmosphere of nitrogen was heated at 80° C. for 18 hours. The mixture was allowed to cool to room temperature, filtered and then evaporated. The residue was dissolved in EtOAc (150 mL) and the mixture washed sequentially with a saturated solution of NaHCO3 (2×100 mL), water (100 mL) and then with a saturated solution of NaCl (100 mL). The organic layer was dried over MgSO4 and then evaporated. The residue was purified by chromatography on silica, eluting with a gradient of 0-100% EtOAc in isohexane. Fractions containing product were combined and evaporated to afford 2-[(2,5-dichloropyridin-4-yl)amino]-6-fluoro-N-methylbenzamide (486 mg, 26% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 2.74 (3H, d), 6.96 (1H, d), 7.15 (1H, ddd), 7.37 (1H, d), 7.54 (1H, td), 8.26 (1H, s), 8.54 (1H, m), 9.09 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+ =314.26 and 316.21 and 318.23.

Provenance & Evidence