Method for preparing 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy) piperidin-1-yl)-prop-2-en-1-one hydrochloride and intermediates used therein

A method for preparing a 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)-prop-2-en-1-one hydrochloride of formula (I), 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 an inert polar protic solvent in the presence of a base to produce a compound of formula (IV);
• (4) subjecting the compound of formula (IV) to a reaction with hydrochloric acid in an inert solvent to produce a compound of formula (III);
• (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);
• and
• (6) subjecting the compound of formula (II) to a reaction with hydrochloric acid to produce the compound of formula (I):