Darunavir amorphous form preparation method

A darunavir and amorphous technology, which is applied in the field of medicinal chemistry, can solve problems such as prolonging the production cycle, prolonging the distillation time, and easy puffing of materials, and achieves the effects of short production cycle, good solubility and simple process

Inactive Publication Date: 2017-06-16
ZHEJIANG JIUZHOU PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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

Method used

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  • Darunavir amorphous form preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Add 50g of isopropyl acetate and 10g of darunavir into a 250ml four-necked bottle, stir, and raise the temperature to 50-60°C; Continue to keep warm for 1‐3 hours. Suction filtration, rinse with n-heptane. The wet product was dried in a vacuum oven at 60°C. 9.3 g of amorphous darunavir was obtained with a purity of 100.0% and a yield of 93.0%. Its XRPD as figure 1 shown.

Embodiment 2

[0040] Add 4g of acetone and 1g of darunavir into a 250ml four-necked bottle, stir, and raise the temperature to 50-60°C; -3 hours. Suction filtration, rinse with n-heptane. The wet product was dried in a vacuum oven at 60°C. Darunavir amorphous 0.95g was obtained with a purity of 99.9% and a yield of 95.0%. Its XRPD as figure 2 shown.

Embodiment 3

[0042] Add 50g of isopropyl acetate and 10g of darunavir into a 250ml four-necked bottle, stir, and raise the temperature to 50-60°C; after the solution is dissolved, add the solution dropwise to -10-0°C n-heptane, and filter with suction , n-heptane rinse. The wet product was dried in a vacuum oven at 60°C. 9.3 g of amorphous darunavir was obtained with a purity of 100.0% and a yield of 93.0%.

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Abstract

The present invention relates to the technical field of pharmaceutical chemistry, particularly to a darunavir amorphous form preparation method. According to the present invention, the preparation method belongs to the anti-solvent method in crystal form preparation screening, wherein the crystal form is screened by using the anti-solvent in the prior art while the final product is the specific crystal form of darunavir such as WO2013114382 and is not the amorphous form; and the preparation method of the present invention is different from the method in the prior art, has the high production capacity, and is suitable for industrial production. The amorphous form of darunavir is defined in the specification.

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...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D493/04
CPCC07D493/04
Inventor 徐建康吴昊叶美其叶恺诸林冰
Owner ZHEJIANG JIUZHOU PHARM CO LTD
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