A kind of synthetic method of 2-amino-n-(2-chloro-6-methylphenyl) thiazole-5-carboxamide

Abstract

The invention relates to a 2-amino-N-(2-chloro-6-methyl phenyl)thiazole-5-carboxamide synthesis method, wherein the compound 2-amino-N-(2-chloro-6-methyl phenyl)thiazole-5-carboxamide is a key intermediate for synthesizing dasatinib. The synthesis method comprises that: 1) trichloroacetyl chloride and ethyl vinyl ether are subjected to a nucleophilic substitution and hydrolysis reaction one-pot method to synthesize 3-ethoxyacrylic acid; 2) 3-ethoxyacrylic acid is subjected to an acyl chlorination and amidation reaction one-pot method to synthesize N-(2-chloro-6-methyl phenyl)-3-ethoxy acrylamide; and 3) N-(2-chloro-6-methyl phenyl)-3-ethoxy acrylamide, NBS and thiourea are subjected to a reaction to obtain 2-amino-N-(2-chloro-6-methyl phenyl)thiazole-5-carboxamide. The synthesis method has characteristics of yield increase, cost reduction, operation simplifying, and high implementation value.

Description

technical field

[0001] The present invention relates to a synthetic method of a pharmaceutical intermediate, especially a synthetic method of 2-amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide, which is a synthetic method of dasatinib a key intermediate. Background technique

[0002] Dasatinib (Dasatinib, trade name Sprycel) is an oral tyrosine kinase inhibitor developed by Bristol-Myers Squibb, its chemical name is N-(2-chloro-6-methylphenyl )-2-[6-[4-(2-Hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino-5-thiazolecarboxamide monohydrate. The drug was approved by the FDA in June 2006 for the treatment of patients with chronic myeloid leukemia who are resistant or intolerant to imatinib; at the same time, it is also used to treat patients with chronic myeloid leukemia who are resistant or intolerant to other therapies. Adult patients with chromosomally positive acute lymphoblastic leukemia. The drug achieved sales of 130 million US dollars in 2009, which sho...

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