PAN Kyk Chan (KR),ПАН Кык Чан (KR),CHON Che Khek (KR),ЧОН Чэ Хёк (KR),MUN Yun Kho (KR),МУН Юн Хо (KR)
申请号：
RU2015129994
公开号：
RU0002671843C2
申请日:
2014.01.27
申请国别(地区):
RU
年份:
2018
代理人:
摘要：
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 exНастоящее изобретение относится к новому способу получения 1-(4-(4-(3,4-дихлор-2-фторфениламино)-7-метоксихиназолин-6-илокси)пиперидин-1-ил)проп-2-ен-1-она формулы (I). Соединение обладает действием селективного ингибитора устойчивости к лекарственному средству, вызванному ростом раковых клеток и мутациями тирозинкиназы. Способ заключается во взаимодействии соединения формулы (II) с соединением формулы (III) в инертном полярном апротонном растворителе в присутствии основания,.Исходное соединение формулы (II) получают (i) путем осуществления взаимодействия соединения формулы (VII) с галогенирующим агент
