4-(4-Amino-3-fluorophenoxy)-N-methylpicolinamide has the appearance of a white to yellow powder or crystals, which is stable and non-reactive under normal conditions of use, storage and transport.
4-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide is a compound used as a reagent to synthesize Regorafenib (R143000), a multikinase inhibitor that is used to treat patients with advanced colorectal cancer.
Under nitrogen atmosphere, 363 g of 4-amino-3-fluorophenol, 374 g of 4-chloro-N-methylpyridine-2-carboxamide and 3740 mL of N,N-dimethylacetamide were sequentially added to the reaction vessel and stirred until completely dissolved. Subsequently, 115 g of sodium hydroxide was added and the temperature of the reaction system was raised to 105 °C and the temperature was maintained for 1 hour. Upon completion of the reaction, 5600 mL of water was added to the system, the mixture was cooled to 10 °C and stirred at this temperature overnight to promote crystallization. After separation by filtration, 509 g of the brown solid product 4-(4-amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide was obtained by drying. The product was analyzed by high performance liquid chromatography (HPLC) and showed a purity of 99.3%, a melting point of 141.5-142.5 °C and a yield of 88.9%.
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