Abstract: OBJECTIVE To study the preparation process of novel small molecule vascular endothelial growth factor receptor inhibitor fruquintinib. METHODS The target compound furaquininib was prepared via nucleophilic substitution, hydrolysis, intramolecular Perkin, Friedel-Crafts acylation, demethylation, amidation and nucleophilic substitution reaction by using 4-methoxy-2-hydroxybenzaldehyde as a raw material. RESULTS The structures of the intermediates and target compound fruquintinib were confirmed by ¹H-NMR, ¹³C-NMR and ESI-MS. CONCLUSION The whole route avoids the exhaust emission problems caused by the use of thionyl chloride, and makes the experimental operation safer. In addition, the target compound is purified by crystallization, which makes workup simpler and more efficient.