The invention belongs to the technical field of drug synthesis, particularly relates to a compound with antitumor activity, and particularly provides a preparation method and application of an imatinib derivative. The preparation method comprises the following steps: with 4-hydroxypyridine and tert-butyl acetate as raw materials, sequentially carrying out an alkenylation reaction, a Michael addition reaction in an ammonia gas atmosphere and the like to obtain 2,6-bis(4-pyridyl)-hexahydropyrimidine-4H-one; and carrying out a reaction on the 2,6-bis(4-pyridyl)-hexahydropyrimidine-4H-one with prepared 2-chloro-4-(pyridine-3-yl)pyrimidine to obtain the imatinib derivative. The imatinib derivative with antitumor activity is simple in synthesis method and low in raw material price.