2,5-Dichloro-4-iodopyridine → 2-(2,5-dichloropyridin-4-ylamino)-4-fluoro-N-methylbenzamide

Participants

Reaction Conditions

Reaction Steps

palladium acetate (31.2 mg, 0.14 mmol) was added to 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (121 mg, 0.21 mmol), Cesium carbonate (2266 mg, 6.95 mmol), 2-amino-4-fluoro-N-methylbenzamide (585 mg, 3.48 mmol) and 2,5-dichloro-4-iodopyridine (1000 mg, 3.65 mmol) in dioxane (40 mL) under nitrogen. The resulting suspension was stirred at 80 °C for 18hrs then cooled. Product and bis product suggested. Disappointing! The reaction mixture was evaporated to dryness and redissolved in EtOAc (150 mL), and washed sequentially with saturated NaHCO3 (2 x 100 mL), water (100 mL), and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered then evaporated. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford desired product as a yellow solid.

Provenance & Evidence