A kind of preparation technology of dasatinib

Abstract

The invention relates to a process for preparing dasatinib. The process includes steps of carrying out heating reflux on 3-oxo-propionic acid ethyl ester and 2-chlorine-6-methylaniline under alkalineconditions, adding cupric bromide, carrying out temperature-rise reflux, adding thiourea and a catalyst heteropoly acid salt, and carrying out room-temperature stirring reaction to obtain 2-amine-N-(2-chlorine-6-methyl phenyl)thiazole-5-formamide; carrying out 'one-pot reaction' on the 2-amine-N-(2-chlorine-6-methyl phenyl)thiazole-5-formamide, 4, 6-dichloro-2-methylpyrimidine and N-hydroxyethyl piperazine under the effects of catalysts to obtain the dasatinib. The process has the advantages of mild condition, simple step, environmental friendliness, high yield and applicability to industrialproduction.

Description

technical field

[0001] The invention relates to the field of drug synthesis, in particular to a preparation process of dasatinib. Background technique

[0002] Dasatinib (Dasatinib, trade name Sprycel), chemical name N-(2-chloro-6-methylphenyl)-2-[6-[4-(2-hydroxyethyl)-1-piper Azinyl]-2-methyl-4-pyrimidinyl]amino-5-thiazole carboxamide is an oral tyrosine kinase inhibitor developed by Bristol-Myers Squibb. The drug was approved by the FDA in June 2006 for the treatment of chronic myelogenous leukemia and also for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. This product has inhibitory effects on various mutants of Bcr-Ab1 kinase, and the inhibitory intensity is much higher than that of Imatinib, and no drug resistance has been found. Its structural formula is as follows:

[0003]

[0004] Regarding the synthesis of dasatinib, there are many domestic and foreign literature reports, most of which are intermediate 2-amino-N-(2-chloro-6-m...

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