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The reaction bottle adding compound IV 31.35 g, cesium carbonate 46.33 g, cuprous chloride 2.84 g, 2,2,6,6-tetramethyl-3,5-heptyldiketone (0.0332 muM), 600 ml N,N-dimethyl-pyrrolidone, control in the 50 - 60 C stirring 30 min, then the compound is added V 24.47 g, stirring to reflux 2 h, TLC monitoring the completion of reaction. After the reaction is concentrated under reduced pressure, ethanol or recrystallization, to obtain the solid sorafenib (I) 42.62 g, the product yield is 96.7%, HPLC purity of 99.98%
(3) 4-[([chloro]-3-(trifluoromethyl) phenyl] amino}carbonyl) Amino] phenol (44.72 g, 6.6 mol) obtained in the step (2) was added (4-hydroxy-6-yl)pyridine-N-methyl-2-carboxamide (40.5 g, 5.25 mol) with a catalyst, followed by heating to effect etherification under controlled temperature conditions to generate 4- {4- [ ([4-chloro-3-(trifluoromethyl)phenyl)]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboxamide (35.9g, 5.6 mol), yield 88.9%.
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