A kind of preparation method of danazol

A danazol and reaction technology, applied in the field of preparation of danazol, can solve the problems of reduced safety, cumbersome methods, hidden dangers and the like, and achieve the effects of short reaction time, high reaction efficiency and simple operation

Active Publication Date: 2020-07-03
JIANGSU LIANHUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, the above-mentioned method has the following disadvantages: 1, the route is too long, the whole preparation step has 5 steps, and the protection and deprotection of the 3-position are used, the method is loaded down with trivial details, and the efficiency is low; 2, in the ethynylation reaction, the easy Inflammable and explosive dangerous acetylene gas, the safety is greatly reduced, and there may be hidden dangers in the process of industrial production and preparation

Method used

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Effect test

preparation example Construction

[0033] A preparation method of danazol is prepared by taking androstenedione as a starting material through 2-position methylation reaction, 17-position carbonylacetylation reaction and oximation reaction.

[0034] The preparation method of danazol provided by the present invention changes the complicated problem of the danazol reaction process in the prior art. It takes androstenedione as the starting material and undergoes a 2-position methylation reaction and a 17-position reaction. Danazol can be prepared by carbonyl acetylation reaction and oximation reaction, and the 2-position methylation reaction and the 17-position carbonyl acetylation reaction are completed in one step. The described has the advantages of safety, short reaction steps, high yield, high efficiency, etc., no flammable and explosive acetylene gas with great safety risks is used in the reaction, and preparation of potassium alkyne with acetylene magnesium bromide and acetylene magnesium chloride safer. At t...

Embodiment 1

[0057] (1) Synthesis of 17-position carbonyl acetylation and 2-position methylolation products

[0058] Add androstenedione (18g, 0.063mol) to 80mL of anhydrous tetrahydrofuran, raise the temperature to 35-45°C and stir the solution, cool to 0-10°C, slowly add acetylene magnesium bromide (190mL, specification 0.5M in THF) After the dripping is completed, the reaction is incubated for 3h, then ethyl formate (25g, 0.337mol) is added, the temperature is raised to 15-20°C, and the reaction is incubated for 5h. After the reaction, the reaction materials were added to 400mL of water for precipitation, filtered, and the filtrate was cooled to about 0°C and adjusted to pH = 1-2 to acidify and precipitate precipitates, filtered, washed with water to neutral, and dried to obtain 17-position carbonyl acetylation and 2-position methylol The product is 18g.

[0059] Results: The yield was 85%, mp182~185℃.

[0060] (2) Synthesis of Danazol

[0061] The 17-position carbonyl acetylation and 2-posit...

Embodiment 2

[0064] (1) Synthesis of 17-position carbonyl acetylation and 2-position methylolation products

[0065] Add androstenedione (27g, 0.095mol) to 120mL of anhydrous tetrahydrofuran, raise the temperature to 35-45°C and stir the solution, lower the temperature to 0-10°C, slowly add acetylene magnesium bromide (300mL, specification 0.5M in THF) dropwise After the dripping is completed, the reaction is kept for 3h, then ethyl formate (40g, 0.539mol) is added, the temperature is raised to 15-20°C, and the reaction is kept for 5h. After the reaction, the reaction materials were added to 600mL of water for precipitation, filtered, and the filtrate was cooled to about 0°C and adjusted to pH = 1-2 to precipitate precipitates, filtered, washed with water until neutral, and dried to obtain 17-position carbonyl acetylation and 2-position hydroxymethyl Chemical product 28g.

[0066] Results: The yield was 88%, mp183~186℃.

[0067] (2) Synthesis of Danazol:

[0068] The 17-position carbonyl acetyla...

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Abstract

The invention provides a preparation method of danazol. According to the preparation method of the danazol, androstenedione is used as an initial raw material, through 2-position secondary hydroxymethylation reaction, 17-position carbonyl ethinylation reaction and oximation reaction, the danazol can be prepared, and the 2-position secondary hydroxymethylation reaction and the 17-position carbonylethinylation reaction are completed in one step. The preparation method of the danazol has the advantages of being safe, short in reaction step, high in yield, efficient in reaction and the like, andin the reaction, no flammable and combustible acetylene gas with huge potential safety hazards is used, so that preparation in which potassiumacetylide is replaced by ethynylmagnesium bromide is safer. Meanwhile, the reaction which needs to be completed in four steps before is completed in one step, the reaction is more efficient, meanwhile, operation is simple, and reaction time is short.

Description

Technical field [0001] The invention relates to the technical field of medicine and chemical engineering, and in particular to a method for preparing danazol. Background technique [0002] Danazol is a synthetic steroidal heterocyclic compound, that is, the derivative of androgen 17a-ethinyl testosterone is a weak androgen, which has anti-gonadotropin effects and mild androgenic effects, and can promote ectopic endometrium Degeneration and improvement of symptoms can also conceive certain infertility patients. For the treatment of endometriosis, it can also be used to treat fibrocystic breast disease, spontaneous thrombocytopenic purpura, hereditary angioedema, systemic lupus erythematosus, male and female breasts, and puberty precocious puberty. [0003] For the preparation of danazol, the latest published patent CN201410281920 introduces the latest and improved preparation method of danazol. The method uses androstenedione as the starting material, through 3 enol etherification...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J71/00
CPCC07J71/0063
Inventor 吴为贲
Owner JIANGSU LIANHUAN PHARMA
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