Method for synthesizing 6-methyl-17alpha- hydroxyl-19-nor-pregnene-4,6-diene-3,20-diketone

A technology of methylpregnantine and norpregnantine, applied in the directions of steroids, organic chemistry, etc., can solve problems such as difficulty in obtaining, and achieve the effects of high yield, reducing the possibility of metal residues, and simple reaction operation.

Active Publication Date: 2015-11-04
丽江华映激素药物科技开发有限公司
View PDF4 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this starting material is very difficult to obtain. At home and abroad, it mai...

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for synthesizing 6-methyl-17alpha- hydroxyl-19-nor-pregnene-4,6-diene-3,20-diketone
  • Method for synthesizing 6-methyl-17alpha- hydroxyl-19-nor-pregnene-4,6-diene-3,20-diketone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] 1.1 3-Ethoxy-17α-ethynyl-19-desmethylpregna-3,5-dien-17β-ol (2)

[0033] Compound 1 (15g, 0.05mol) was dissolved in THF (150ml) and added to the reaction flask, then triethyl orthoformate (14.8g, 0.1mol) and p-toluenesulfonic acid (0.15g, 0.8mmol) were added. The reaction solution was stirred at 25°C for 12 hours, pyridine (3ml) was added, most of the solvent was evaporated under reduced pressure, cooled and filtered, and dried to obtain 15g of the product with a yield of 92%. HNMR (ppm, CDCl 3 ):5.65(s,1H),4.73(s,1H),3.72-3.82(q,2H),3.35(s,1H),3.14(b,1H),2.20-2.60(m,5H),1.80- 2.10(m,6H),1.20-1.60(m,8H),0.95-1.05(m,2H),0.72(s,3H).

[0034]1.2 3-Ethoxy-6-formyl-17α-ethynyl-19-desmethylpregna-3,5-dien-17β-ol (3)

[0035] Add compound 2 (14g, 0.043mol), DMF (100ml) into the reaction flask, stir to dissolve, cool to -20°C, add Vilsmeier reagent dropwise, react for 15 minutes, pour the reaction solution into saturated sodium bicarbonate solution (400ml), suction filtrati...

Embodiment 2

[0045] 2.1 3-Ethoxy-17α-ethynyl-19-desmethylpregna-3,5-dien-17β-ol (2)

[0046] Compound 1 (15g, 0.05mol) was dissolved in THF (150ml) and added to the reaction flask, then triethyl orthoformate (14.8g, 0.1mol) and p-toluenesulfonic acid (0.15g, 0.8mmol) were added. The reaction solution was stirred at 80° C. for 3 hours, pyridine (3 ml) was added, the solvent was evaporated under reduced pressure, filtered with suction, and dried to obtain 13.5 g of the product with a yield of 83%. The product analysis result is consistent with the product obtained in Example 1.1.

[0047] 2.2 3-Ethoxy-6-formyl-17α-ethynyl-19-desmethylpregna-3,5-dien-17β-ol (3)

[0048] Compound 2 (13g, 0.040mol), DMF (100ml) was added to the reaction flask, stirred and dissolved, cooled to 0°C, Vilsmeier reagent was added dropwise, reacted for 15 minutes, and the reaction solution was poured into saturated sodium bicarbonate solution ( 400ml), 12.8g of the product was obtained after recrystallization, and ...

Embodiment 3

[0058] 3.1 3-Ethoxy-17α-ethynyl-19-desmethylpregna-3,5-dien-17β-ol (2)

[0059] Compound 1 (15g, 0.05mol) was dissolved in THF (150ml) and added to the reaction flask, then triethyl orthoformate (14.8g, 0.1mol) and p-toluenesulfonic acid (0.15g, 0.8mmol) were added. The reaction solution was stirred at 60° C. for 4 hours, pyridine (3 ml) was added, the solvent was removed under reduced pressure, and the product was dried to obtain 14.3 g with a yield of 87%. The product analysis result is consistent with the product obtained in Example 1.1.

[0060] 3.2 3-Ethoxy-6-formyl-17α-ethynyl-19-desmethylpregna-3,5-dien-17β-ol (3)

[0061] Add compound 2 (14g, 0.043mol), DMF (100ml) into the reaction flask, stir to dissolve, cool to 0-5°C, add Vilsmeier reagent dropwise, react at 5-10°C for 10 minutes, pour the reaction solution into In saturated sodium bicarbonate solution (300ml), 12.2g of the product was obtained after recrystallization, with a yield of 80%. The product analysis r...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to the field of pharmaceutical synthesis, in particular to a method for synthesizing 6-methyl-17alpha- hydroxyl-19-nor-pregnene-4,6-diene-3,20-diketone. The method comprises the steps of reacting norethisterone with ethylorthoformate to obtain 3-ethoxy-17alpha-acetenyl-19-demethyl-pregnene-3,5-diene-17beta-alcohol (2); causing the compound (2) to undergo Vilsmeier reaction to obtain 3-ethoxy-6-formoxyl-17alpha-acetenyl-19- demethyl-pregnene-3,5-diene-17beta-alcohol (3); reacting the compound (3) with NaBH4 and obtaining 6-methine-17alpha-acetenyl-17beta-hydroxyl-19-demethyl-pregnene-4-en-3-ketone (4) through acidification and dehydration; causing the compound (4) to undergo double bond shift under the effect of Pd-C/cyclohexene to obtain a product 6-methyl-17alpha-acetenyl-17beta-hydroxyl-19-demethyl-pregnene-4,6-diene-3-ketone (5); and reacting the compound (5) with benzene sulfenyl chloride to obtain 6-methyl-19-demethyl-21-phenylsulfinyl-pregnene-4,6,17(20)20-tetraene-3-ketone.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular, the invention relates to a method for synthesizing 6-methyl-17α-hydroxyl-19-norpregna-4,6-diene-3,20-dione. Background technique [0002] 6-Methyl-17α-hydroxyl-19-norpregna-4,6-diene-3,20-dione (structural formula 1) is an important intermediate in the synthesis of nomegestone, which passes through and acetic anhydride The esterification reaction will form the fourth-generation progestin nomegestrol. [0003] [0004] Nomegestrol is a new type of high-efficiency oral progestin, which has the characteristics of good contraceptive effect, small toxic and side effects, convenient use and safety. In addition, nomegestone has a good effect on endometrial displacement syndrome (Chinese Pharrnacological Bulletin2004Nov; 20(11): 1215-7) and reversal of multidrug resistance of breast cancer cell lines (China Oncol.March2002Vol24. No.2). Due to the great difficulty in the synthesis of nom...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07J7/00
CPCC07J7/002
Inventor 黄云生陆何林朱焰
Owner 丽江华映激素药物科技开发有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap