Synthesis of poziotinib derivative

A method for preparing a compound of formula (II), which comprises the steps of:

• (1) subjecting a compound of formula (VIII) to a reaction with a halogenating agent in the presence of an organic base, followed by a reaction with a compound of formula (X), to produce a compound of formula (VI);
• (2) subjecting the compound of formula (VI) to a reaction with an ammonia solution in a polar protic solvent to produce a compound of formula (V);
• (3) subjecting the compound of formula (V) to a reaction with a compound of formula (IX) in a polar aprotic solvent system in the presence of a base to produce a compound of formula (IV), wherein the polar aprotic solvent system comprises at least one selected from the group consisting of acetonitrile, acetone, dichloromethane, chloroform, carbon tetrachloride, 1,4-dioxane, ethyl acetate, tetrahydrofuran, and any combination thereof;
• (4) subjecting the compound of formula (IV) to a reaction with an acid (HA) in an inert solvent to produce a compound of formula (III);
• and
• (5) subjecting the compound of formula (III) to an acrylation reaction with
• (wherein X is halogen) in the presence of a base to produce a compound of formula (II)