Preparation method of enzalutamide

Abstract

The invention provides a preparation method of enzalutamide. The method comprises the following steps: adding a compound with formula F to a solvent; reacting with a methylamine source; and after the reaction, collecting the compound with formula G from the reaction products, so as to obtain the enzalutamide. The invention overcomes the major problems of the prior art, gets rid of the time-consuming and labor-consuming operation such as column chromatography, gets rid of the highly toxic reagent such methyl iodide, and has the advantages of mild reaction conditions, simple and easy post-treatment, increased overall yield, reaction time reduction, production cost reduction, and applicability to industrial scale-up. The reaction general formula is as below.

Description

technical field

[0001] The invention relates to a preparation method of Enzalutamide, a drug for treating hormone-refractory prostate cancer. Background technique

[0002] Enzalutamide (Enzalutamide) is an androgen receptor antagonist developed by Medivation Corporation of the United States, Medivation and Japan Astek Corporation, and its chemical name is 4-(3-(4-cyano-3-(trifluoromethyl )phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide, has divergent castration for treatment Refractory prostate cancer has a special effect.

[0003] The methods for preparing enzalutamide in the prior art mainly include:

[0004] CN101333922B discloses a method for preparing enzalutamide, as shown in Scheme 1 below:

[0005]

[0006] This route uses nitrotoluene derivatives as raw materials to prepare the target product through 6-step reactions such as oxidation, amidolysis and reduction, and mainly has the following defects:

[0007] 1) The yield of the...

Images