Momertasone furoate intermediate 21-hydroxyl preparing process

A hydroxyl and dihydroxy technology, applied in the preparation of steroids, chemical instruments and methods, steroids, etc., can solve the problems of relying on imports, structure and physical and chemical properties that have not been reported, and achieve the effect of localization

Active Publication Date: 2008-05-21
天津药业集团有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] From the above, it can be seen that most of the synthetic methods of mometasone furoate abroad are based on compound 4 as a raw material, and the specific structure and physical and chemical properties of this compound have not been reported. Therefore, the domestic production of mometasone furoate raw material can only rely on imports

Method used

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  • Momertasone furoate intermediate 21-hydroxyl preparing process
  • Momertasone furoate intermediate 21-hydroxyl preparing process

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Compound 9β, 11β-epoxy-17α, 21-dihydroxy-16α-methyl-1,4-pregnadiene-3,20-dione provided by the present invention consists of 9β, 11β-epoxy-17α, 21 -Dihydroxy-16α-methyl-1,4-pregnadiene-3,20-dione, 21-ester [compound 3] is prepared by hydrolysis, the specific process is as follows:

[0022] Add 0.5g of compound 3, 13mL of methanol and start stirring, continue to add methanol until compound 3 is completely dissolved, drop the temperature at 0-5°C and add NaOH-MeOH solution dropwise, follow the reaction with TLC, stop the dropwise addition after the reaction is complete, stop stirring, Filtration, the filtrate was concentrated to precipitate a white solid, which was filtered and dried to obtain the finished compound.

[0023] Pass the obtained finished compound through a chromatographic column, the mobile phase is chloroform:methanol=10:3, and obtain the refined compound.

Embodiment 2

[0025] The above compound 3 is obtained by substitution of 9β, 11β-epoxy-17α-hydroxyl-16α-methyl-21-iodo-1,4-pregnadiene-3,20-dione [compound 2], the specific process as follows:

[0026] Dissolve 3.0g of iodide (compound 2) and 4.0g of potassium acetate in 15mL of DMF at room temperature, and then raise the temperature according to a gradient: 1 hour to 30°C → 1 hour to 40°C → 1 hour to 50°C, at 50 ℃ for another 1 hour to cool down for post-treatment to obtain the crude product of compound 3.

[0027] The crude product of compound 3 was passed through the chromatographic column, and the mobile phase was chloroform:methanol=5:1, and the final refined product compound 3 was obtained.

[0028] The chemical reaction formula is:

[0029]

[0030] Structural characterization of compound 3

[0031] Elemental Analysis C 24 h 30 o 6

[0032] Measured value (%): C69.42, H7.14;

[0033] Calculated (%): C69.56, H7.24.

[0034] Elemental analysis (MS (FAB)), infrared spectrosc...

Embodiment 3

[0036] The above-mentioned compound 2 was obtained by iodination of 9β, 11β-epoxy-17α-hydroxyl-16α-methyl-1,4-pregnadiene-3,20-dione (compound 1), and the specific process was as follows:

[0037]Add 6mL of methanol and 0.5g of calcium chloride, stir to dissolve, then add chloroform to dissolve 3.56g of compound 1, cool down to below 10°C after dissolution, add calcium oxide, and continue to drop to 0°C (0°C±2°C) . Add 2.55 g of iodine solution dropwise, and continue to insulate and stir for 1 hour after dropping. Then lower it below 0°C, add the pre-cooled ammonium chloride aqueous solution, stand still for 30 minutes after adding, filter the chloroform layer, extract the water layer with 12mL chloroform four times, combine the chloroform solution, concentrate to nearly dry, add 1.5mL methanol , continued to concentrate, and filtered to obtain light yellow solid compound 2.

[0038] The chemical reaction formula is:

[0039]

[0040] Structural characterization of compo...

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Abstract

The present invention is compound 9beta, 11beta-epoxy-17alpha, 21-dihydroxy-16alpha-methyl-1, 4-pregnanediene-3,20-dione, as the momertasone furoate intermediate, and its production process. The intermediate 9beta, 11beta-epoxy-17alpha, 21-dihydroxy-16alpha-methyl-1, 4-pregnanediene-3,20-dione is prepared through hydrolyzing 9beta, 11beta-epoxy-17alpha, 21-dihydroxy-16alpha-methyl-1, 4-pregnanediene-3,20-dione, 21-ester (compound III) and the preparation process includes the following steps: dissolving compound III in methanol completely; dropping NaOH-MeOH solution after lowering the tempera ture to 0-5 deg.c to produce TLC tracking reaction and stopping dropping after finishing reaction; filtering and concentrating the filtrate to separate out white solid; filtering and drying to obtain the target product.

Description

【Technical field】: [0001] The invention relates to an intermediate of mometasone furoate, in particular to 9β, 11β-epoxy-17α, 21-dihydroxy-16α-methyl-1,4-pregnadiene-3,20- Process for the preparation of diketones. 【Background technique】: [0002] Mometasone furoate (Mometasone Furoate, Sch 32088), scientific name 9α, 21-dichloro-17α-(2-furoyl)-11β-hydroxy-16α-methyl-pregna-1,4-diene- 3,20-diketone is a new drug developed in the 1980s and produced by Schering Company in the United States. It was first launched in the United States in 1987, and the Canadian Schering-Plough Company obtained permission to enter the Chinese market in 1995. In 1997, Shanghai Schering-Plough Company was approved by the Ministry of Health of my country to start producing ointment preparations, and all required raw materials were imported. The biggest feature of the drug is a powerful topical corticosteroid preparation, and the American Psoriasis Foundation recommends this product as the first cho...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J7/00C07J75/00
Inventor 李平丁丽李金禄
Owner 天津药业集团有限公司
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