PROCESS FOR THE PREPARATION OF CERITINIB USING IN SITU PREPARED 5-METHYL-2-(1 -METHYLETHOXY)-4-(4-PIPERIDINYL)-BENZENAMINE MONOHYDROCHLORIDE (1 :1 ) AS AN INTERMEDIATE

摘要

The object of the invention is a preparation method of Ceritinib of formula (I) and its salts wherein 2-isopropylthioaniline is used in the first step. Even under mild conditions, it provides an intermediate, which is further oxidized to a sulfone in a high yield. The sulfone is subsequently transferred by means of a one-step reaction to Ceritinib of formula I in the form of a salt either through a reaction with the intermediate of formula (V) catalyzed by an acid, or in neutral conditions with its unprotected analog of formula (IX), which is in the form of the in-situ generated monohydrochloride. The product is easily isolated from the reaction as crystalline Ceritinib of formula (I) in the form of the salt with hydrochloric acid.