Synthesis Of Antitumor Drug Dasatinib

Objective Dasatinib is an oral tyrosine kinase inhibitor, can have very good effect on the treatment of adult chronic leukemia and in leukemia treatment failure or intolerance of the patients, but also can be used for the treatment for adult chronic myeloid leukemia imatinib resistant or intolerant and Philadelphia chromosome positive acute lymphatic mother cell leukemia. At present, did not find any resistance, has good curative effect on the patients. The drug is approved in the domestic only Zhengda fine a pharmaceutical production. In recent years, dasatinib, a sharp increase in sales, visible dasatinib has good curative effect and broad prospects for sales. Therefore, to dasatinib synthesis process was improved, reducing the cost, improving the yield, which is of great significance for industrial production.Methods This experiment first by( E)-N-(2-chloro-6-methyl phenyl)-3-ethoxy acrylamide as the starting material reaction, make the amide and thiourea occurs after the cyclization reaction to generate 2-amino-N-( 2-chloro-6-methyl phenyl)-5-thiazole carboxamides, again with the formation of 2-4,6-two-2-methyl pyrimidine in chlorine tetrahydrofuran(6-chloro-2-methyl pyrimidine-4-amino-N-(-6-)2-chloro methyl phenyl)-5- thiazole carboxamides, finally in N, catalyzed by N- two isopropyl ethylamine, and 1-(2-hydroxyethyl) piperazine reaction to prepare the dasatinib; through the orthogonal experiment on for the synthesis conditions were optimized.Results Through the optimization for the reaction conditions of orthogonal experiment on dasatinib finished product synthesis, the final result of the molar yield: 54.7%, to verify the purity by high performance liquid chromatography is: 99.91%, the use of modern analytical instrument that are ultraviolet spectroscopy( UV),infrared spectroscopy( IR),nuclear magnetic resonance spectroscopy(NMR)mass spectrometry(MS)etc. characterization of the structure, confirmed the structure of synthetic product.Conclusions Through the experiment the optimization conditions are obtained for the molar yield increased by 3.2%, the experimental reaction can reduce reaction cost; and through to the reaction solvent, catalyst, reaction temperature, reaction time and other improvements, simplifies the operation method, improve the yield, is conducive to industrial production.