Cesium carbonate → 2-[(2,5-dichloropyridin-4-yl)amino]-3-fluoro-N-methylbenzamide

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Reaction Conditions

Reaction Steps

Palladium(II) acetate (35.9 mg, 0.16 mmol) was added to 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (139 mg, 0.24 mmol), cesium carbonate (2604 mg, 7.99 mmol), 2,5-dichloro-4-iodopyridine (1094 mg, 4.00 mmol) and 2-amino-3-fluoro-N-methylbenzamide (672 mg, 4.00 mmol) in dioxane (20 mL) under an atmosphere of nitrogen. The resulting suspension was heated at 80° C. for 24 hours and then allowed to cool to room temperature. The mixture was evaporated and the residue dissolved in EtOAc (150 mL) and then washed sequentially with a saturated solution of NaHCO3 (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 evaporated to afford 2-[(2,5-dichloropyridin-4-yl)amino]-3-fluoro-N-methylbenzamide (624 mg, 50% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 1H NMR (300.132 MHz, DMSO) δ 2.74 (3H, d), 6.39 (1H, d), 7.42 (1H, td), 7.49-7.59 (2H, m), 8.25 (1H, s), 8.64 (1H, m), 9.31 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+ =314.20 and 316.20 and 318.17.

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