Preparation method of dutasteride

Abstract

The invention relates to a preparation method of dutasteride. The method comprises the following steps: preparing acyl chloride from a compound shown in the formula (1), performing an amidation reaction with 2,5-bis(trifluoromethyl)aniline to obtain a compound shown in the formula (2), and performing 1,2-dehydrogenation to obtain dutasteride shown in the formula (3). The preparation method provided by the invention has the following advantages: the reaction conditions are mild, the intermediate of each step can be purified easily, and the quality is stable and controllable; the yield is higher, and the cost is low; and the method is suitable for industrial production. The formula (1) is shown in the description.

Description

technical field The invention belongs to the field of medicine, relates to a preparation method of a compound, in particular to a preparation method of dutasteride. Background technique Benign prostatic hyperplasia (benign prostate hyperplasia, BPH) is a common chronic disease in middle-aged and elderly men. Exhausted. The clinically used drugs for the treatment of BPH mainly include finasteride and dutasteride. Dutasteride is a dual inhibitor of type I and type II 5α-reductase. Its therapeutic effect is better than that of finasteride, and its side effects are lower. It is expected to become a good drug for the treatment of BPH. The chemical name of dutasteride is: N-[2,5-bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide , the structural formula is (3). There are many synthetic methods of dutasteride, first seen in the patent WO9507927A1, wherein the first route is shown as follows: with pregnenone acid (4) as the starting material, the 20-positi...

AI Technical Summary

Problems solved by technology

After experimental verification, the disadvantage of this route is that the solubility of compounds (1) and (10) is all poor, and they are not easily soluble in conventional solvents such as alcohol solvents, ester solvents, and ether solvents. Carry out 1, The 2-position dehydrogenation and amidation reactions will affect the progress of the reaction, the raw materials are difficult to react completely, and the reaction yield is lower than 50%, which is not conducive to the purification of the product, but also unfavorable for industrialized large-scale production

The amidation methods of the existing technology are mainly the thionyl chloride method and the oxalyl chloride method. These methods are used in the preparation of dutasteride, which will lead to incomplete reaction of raw materials, low yield, and the solvent used in the reaction system Such as tetrahydrofuran, toluene, dichloromethane etc. are all poor to the dissolubility of compound (1) or (10), are unfavorable for the carrying out of reaction