METHOD OF OBTAINING HYDROCHLORIDE OF 1-(3,4-DICHLORO-2-FLUOROPHENYLAMINO)-7-METHOXYQUINAZOLIN-6-YLOXY)PIPERIDIN-1-YL)PROP-2-EN-1-ONE AND INTERMEDIATE COMPOUNDS, APPLIED IN IT Russian patent published in 2015 - IPC C07D401/12 

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of obtaining hydrochloride of 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)propen-2-en-1-one of formula (I) . The claimed compound selectively and effectively inhibits the growth of cancer cells, induced by the ultra-expression of the epidermal growth factor receptor (EGFR), and prevents the development of resistance to the medication, caused by tyrosinekinase mutation. The method includes the following stages: (1) carrying out a reaction of the formula (VIII) compound with a halogenating agent in the presence of an organic base, with the following carrying out a reaction with the compound of formula (X) with obtaining the formula (VI) compound; (2) carrying out a reaction of the formula (VI) compound with an ammonia solution in a polar protic solvent with obtaining the formula (V) compound; (3) carrying out a reaction of the formula (V) compound with the compound of formula (IX) in an inert polar protic solvent in the presence of a base with obtaining the formula (IV) compound; (4) carrying out a reaction of the formula (IV) compound with hydrochloric acid in an inert solvent with obtaining the formula (III) compound; (5) acrylation of the formula (III) compound with the compound (where X stands for halogen) in the presence of a base with obtaining the formula (II) compound; and (6) carrying out a reaction of the formula (II) compound with hydrochloric acid with obtaining the formula (I) compound. The intermediate compounds (III), (IV) and (V) are novel. A series of side reactions are eliminated and the general output (from 13% to 95%) and the quality of the target product are considerably increased.

EFFECT: method makes it possible to simplify the process.

18 cl, 2 tbl, 6 ex