Tucatinib is a new generation of tyrosine kinase inhibitor.In order to meet clinical require-ment,the compound 7 was prepared from 2-amino-5-nitrobenzonitrile and N,N-dimethylformamide dimethyl acetal(DMF-DMA)via condensation.Next,it was reduced with zinc powder and reacted with carbon disulfide in the presence of triethylamine to provide triethylamine dithiocarbamate.It was subjected to cyclize with 2-amino-2-methyl-1-propanol using copper bromide to give oxazole intermedi-ate 17.Finally,Tucatinib was synthesized from 4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-meth-ylaniline(6)and 17 with 58.5％yield.The single crystal structure of Tucatinib monohydrate was col-lected through single crystal X-ray diffraction.Along with 1H NMR and 13 C NMR spectrum analysis the structure of the product was confirmed.This methodology has advantages of short synthetic steps and simple post-treatment.It has a good industrial aspect.
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