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Preparation method of 11-ene steroid compound

A technology of compounds and enosteroids, which is applied in the field of preparation of 11 enosteroids, can solve the problems of unsuitability for industrial production, high price, and high price of fluorine reagents, etc.

Active Publication Date: 2019-10-01
TIANJIN PHARMA GROUP CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The published methods for preparing 11,12-ene all use fluorine reagents at present: Avery et al. published in Journal of Medicinal Chemistry; 1990, p1852-1858 articles and patent US5646136 all use DAST (CarbolabsInc) fluorine reagents as dehydrating agent, patent In US4172075, piperidine sulfur trifluoride is used as dehydration reagent, and in WO9518621, fluorine reagent (Et 2 NSF 3 ) as a dehydration reagent, the fluorine reagent used in the reported method is expensive, and the yield is 53%-93%
These fluorine reagents are very expensive, and there are 9,11 ensteroids in the products, which are not suitable for industrial production

Method used

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  • Preparation method of 11-ene steroid compound
  • Preparation method of 11-ene steroid compound
  • Preparation method of 11-ene steroid compound

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Embodiment 1

[0044]

Embodiment 1-1

[0046] Compound 1 (5g, 13.5mmol) was dissolved in acetonitrile (100ml), trimethyl iodosilane (3.8ml, 27.0mmol) was added, and the reaction was stirred at 50°C. The reaction progress was monitored by TLC until the reaction was complete, and Na 2 S 2 o 3 aq (300ml, 10% w / v) to terminate the reaction, add 200ml ethyl acetate to extract and separate liquid, after vacuum distillation, obtain white solid 2-1 (4.4g) by recrystallization from ethyl acetate / petroleum ether, purity 99.2% , 92% molar yield. A small amount of compound 2 was detected in the mother liquor.

Embodiment 1-2

[0048] Compound 1 (5g, 13.5mmol) was dissolved in acetonitrile (100ml), trimethyl iodosilane (5.8ml, 40.5mmol) was added, the reaction was stirred at 50°C, the reaction progress was monitored by TLC, until the reaction was complete, Na 2 S 2 o 3aq (300ml, 10% w / v) terminated the reaction, separated the liquids, extracted the liquids with 200ml ethyl acetate, combined the organic phases for vacuum distillation, and obtained white solid 2 (4.4g) by recrystallization from ethyl acetate / petroleum ether. The purity is 98.5%, and the molar yield is 92%. It was detected that a small amount of compound 2-1 was formed in the mother liquor.

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Abstract

The invention provides a preparation method of a 11-ene steroid compound. A compound shown in a formula I is used as a substrate, a trimethylhalosilane is used as a dehydrating agent, and a dehydration reaction is carried out in an aprotic reaction solvent so as to form the 11-ene steroid compound II; the trimethylhalosilane is selected from one or more of trimethylchlorosilane, trimethylbromosilane and trimethyliodosilane. The preparation method of the 11-ene steroid compound has the beneficial effects of being mild in reaction conditions, environmentally-friendly, easy to operate, low in cost and high in mole yield; the trimethylhalosilane used as the dehydrating agent is cheap and easy to obtain; the new process provided by the invention has an industrialization value, can effectively control side reactions, and improves the reaction yield and quality.

Description

technical field [0001] The invention belongs to the field of chemical medicine synthesis, and in particular relates to a preparation method of 11-en steroid compounds. Background technique [0002] In the field of steroid drug synthesis, the 9 and 11 double bonds of the commonly used intermediate steroid rings are mostly easy to form, but basically all 11, 12-alkene isomers are formed, and the products need to be purified. [0003] When the 9th position is H, the document "Journal of the Chemical Society, 1983, p.2669-2674" uses the reagent N-bromosuccinimide (NBS) to dehydrate in pyridine, and the products obtained are mostly 9 , 11 ensteroids, containing 5% of 11,12 ensteroids. The document "Journal of the Chemical Society; (1955); p3420-3425" needs to form acetate first, and then heat it at a high temperature of 300°C. This method requires high temperature, which is not conducive to the realization of operation, and the product has a mixture of dienes. Chromatographic p...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J7/00C07J5/00C07J71/00
CPCC07J7/0055C07J5/0076C07J7/0085C07J7/003C07J7/0045C07J71/001C07J5/0015Y02P20/55
Inventor 李亚玲孙建磊
Owner TIANJIN PHARMA GROUP CORP
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