Novel industrial synthetic method of dasatinib

Abstract

The invention discloses a novel industrial synthetic method of dasatinib, wherein the needed component dasatinib is finally generated through conversion of an intermediate. The invention discloses a novel method for preparing the dasatinib. According to the preparation method of the dasatinib disclosed by the invention, the synthetic steps are fewer, the raw materials adopted are cheap and easy to obtain, the environment is less polluted, and the yield is high, so that the preparation method of the dasatinib is appropriate for industrial production.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a new industrial synthesis method of Dasatinib. Background technique [0002] The trade name of Dasatinib is SPRYCEL TM , the chemical name is N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4- Pyrimidinyl]-amino]-5-thiazole carboxamide is an oral multiple tyrosine kinase inhibitor developed by Bristol-Myers Squibb, the inhibited kinases include Bcr-Ab1, Src kinase family, c-Kit and PDGFR- β etc. Dasatinib monohydrate passed the priority approval of the US FDA in 2006. It is clinically used for the treatment of chronic myeloid leukemia and also for the treatment of benign Philadelphia-stained acute lymphoblastic leukemia. This product has inhibitory effect on various mutants of Bcr-Ab1 kinase, and the inhibitory intensity is greatly improved compared with Imatinib, and no drug resistance has been found. [0003] [0004] Regarding the synthe...

AI Technical Summary

Problems solved by technology

[0011] Route one route is longer, and total yield is low; Although route two reduces steps relative to route one, the problem that these two routes all exist is: one, the starting material 2-amino-5-thiazole carboxylic acid that adopts Ethyl ester is relatively expensive; second, chlorinated reagents such as thionyl chloride, phosphorus oxychloride, etc., which are volatile and pollute the environment are used in the reaction process

[0019] Route 3 and route tetrathiazole ring are all obtained by closed-loop method, but the raw material 2-methyl-4-amino-6-chloropyrimidine used in route 3 is relatively expensive and not suitable for purchase; although route 4 adopts cheap 4, 6-dichloro-2-methylpyrimidine replaced 2-methyl-4-amino-6-chloropyrimidine, and thiourea replaced the more expensive ethyl isothiocyanate, but the two routes used The price of NBS is relatively expensive

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