Preparation method of darunavir in amorphous form

Abstract

The invention relates to the technical field of medical chemistry, in particular to a preparation method of darunavir in an amorphous form. The preparation method belongs to an anti-solvent method incrystal form preparation screening; although anti-solvents are already used to screen crystal form in the prior art, specific crystal forms of darunavir rather than the amorphous form like WO2013114382 are finally obtained. Different from the prior art, the preparation method has the advantages of being high in productivity and suitable for industrial production.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a method for preparing amorphous darunavir. Background technique [0002] In the research and development of pharmaceutical crystal forms, polymorphic screening and salt-forming screening are the most selected research methods. Polycrystalline screening is to use a certain method to make the compound form polycrystalline in various solvents. The main methods used in polycrystalline screening are: suspension equilibrium method, solvent heating and cooling method, natural evaporation method of saturated solution, and anti-solvent addition method. Salt-forming screening is the reaction between drugs and different counter ions (acids or bases) to form salts, and the interaction between drugs and acid-base molecules mainly occurs in the form of ionic bonds. [0003] Darunavir, the chemical name is [(1R,5S,6R)-2,8-dioxobicyclo[3.3.0]-decane-6-yl]-N-[(2S,3R)-4-[ (4-aminop...

AI Technical Summary

Problems solved by technology

Usually, there are the following disadvantages in the preparation of amorphous form by evaporation and concentration: first, the material is easy to expand, and if special vacuum equipment is needed during industrial production, the production capacity will be reduced; second, after industrial production, due to the increase in the amount of solvent, there will be As a result, the distillation time becomes longer, which leads to a longer production cycle, and a large amount of waste gas is also produced during the vacuum concentration process.

Although the anti-solvent addition method is used in this patent application, there is no disadvantage of the vacuum concentration process, but the final preparation is the solvent-free darunavir crystal form, not its amorphous form

[0008] For example, Chinese patent CN103509031 (applicant: Shanghai Desano, publication date: 2014-1-15) discloses the process of preparing darunavir in which the anti-solvent is water. In order to reduce the temperature, the dissolving solvent in its embodiment 2 The amount of use is very large, which will cause a lot of energy consumption in solvent recovery, which is not economical and environmentally friendly

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