The intermediate 4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylaniline was obtained from 2-amino-4-chloropyridine with a total yield of 28.8% through five steps of condensation, substitution, cyclization, Ullmann reaction and reduction of nitro group. Secondly, 2-amino-5-nitrobenzonitrile was used as starting materials to synthesize the target intermediate N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine via condensation, cyclization and reduction reaction with a total yield of 47.4%. In addition, 4,5-dihydro-4,4-dimethyl-2-(methylthio)oxazole trifluoromethanesulfonate was prepared in two steps under mild conditions in 68.6% yield using carbon disulfide and 2-amino-2-methyl-1-propanol as raw material. Finally, tucatinib was obtained from N4-[3-methyl-4-([1,2,4]triazolo[1,5-a] pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine and 4,5-dihydro-4,4-dimethyl-2-(methylthio)oxazole trifluoromethanesulfonate using triethylamine as base with a yield of 62.8% and HPLC purity of 99.08%. The structures of the products were characterized by 1HNMR, 13CNMR and HRMS analysis. The raw materials are cheap and easy to obtain. This synthetic route provides a theoretical basis for the scale-up production of tucatinib.