A kind of new synthetic method of dasatinib

Abstract

The invention discloses a novel synthetic method of dasatinib. The method has few steps and simple operation, uses cheap and easily obtained raw materials, and is applicable to industrialized production.

Description

[0001] Technical field: [0002] The invention relates to the field of medicinal chemistry, in particular to a new synthesis method of Dasatinib. [0003] Background technique: [0004] Dasatinib (Dasatinib) trade name 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 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. [0005] [0006] Regarding the ...

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Problems solved by technology

[0017] Route 3 is somewhat similar to route 4. The raw material 2-methyl-4-amino-6-chloropyrimidine used in route 3 is relatively expensive and not suitable for purchase; although route 4 uses cheap 4,6-dichloro-2- Methylpyrimidine replaced 2-methyl-4-amino-6-chloropyrimidine, and thiourea replaced the more expensive ethyl isothiocyanatoformate, but the starting material (E) used in the two routes -3-Ethoxyacryloyl chloride is highly volatile and difficult to store; to prepare this raw material by yourself, you need to use dangerous vinyl ether as the starting material to react with triphosgene, which is not very conducive to industrial production

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