METHOD FOR PREPITRING 1-(4-(4-(3,4-DICHLORO-2-FLUOROPHENYLAMINO)-7-METHOXY-QUINAZOLINE-6-YLOXY)-PIPERIDIN-1-YL)PROP-2-EN-1-ONE Russian patent published in 2018 - IPC C07D401/12 A61P35/00 

FIELD: chemistry.

SUBSTANCE: present invention relates to a novel method for preparing 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)prop-2-en-1-one of the formula (I). Compound represents a selective drug resistance inhibitor caused by the growth of cancer cells and tyrosine kinase mutations. Method comprises the step of allowing the compound of formula (II) to react with the compound of formula (III) in an inert polar protic solvent in the presence of a base, (I). (II). (III). Starting compound of formula (II) is obtained (i) by reacting a compound of formula (VII) with a halogenating agent in the presence of an organic base to give a compound of formula (VI) which is then reacted with a compound of formula (VIII) to obtain a compound of formula (V); and by (ii) reacting a compound of formula (V) with an ammonia solution in a polar protic solvent (V) (VI) (VII) (VIII). Compound of formula (III) is prepared by reacting a compound of formula (IX) or a salt thereof with a compound of formula (X) in the presence of a base or an amide coupling agent (IX) (X).

EFFECT: process makes it possible to obtain the intermediates and the target compound in high yield and purity and is simpler than previously known methods, since it does not require additional steps to obtain a double bond in the side chain of the compound.

13 cl, 2 ex