CAS: 53016-31-2; (8R,9S,10R,13S,14S,17R)-13-Ethyl-17-Ethynyl-3-Hydroxyimino-1,2,6,7,8,9,10,11,12,14,15,16-Dodecahydrocyclopenta[a]Phenanthren-17-Ol

上下游产品

炔诺肟酯 Norgestimate 35189-28-7
左炔诺孕酮 Levonorgestrel 797-63-7

📜左炔诺孕酮置于吡啶,盐酸羟胺体系中,用 乙腈 作为反应溶剂,以86%的收率获得产物甲基孕酮
参考文献:Process For The Preparation Of Norelgestromin
标题:Process For The Preparation Of Norelgestromin
摘要:制备诺醇酮或17α-羟基-13β-乙基-18,19-二去甲孕-4-烯-20-炔-3-酮肟的过程,尤其是以晶体形式进行,其e/z异构体比例在1.3至1.5之间.

专利信息

专利号:EP-1641812-B1
优先权日:2003-06-30
标题 :PURE d-(17alpha)-13-ETHYL-17-HYDROXY-18,19-DINORPREGN-4-ENE-20-YNE-3-ONE-3E- AND -3Z-OXIME ISOMERS, AS WELL AS PROCESS FOR THE SYNTHESIS OF THE MIXTURE OF ISOMERS AND THE PURE ISOMERS
发明人：TUBA ZOLTAN; MAHO SANDOR; KESERU GYOERGY; KOZMA JOZSEF; HORVATH JANOS; BALOGH GABOR
权利人:RICHTER GEDEON NYRT
摘要:The invention relates to the pure d-(17alpha)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-­20-yne-3-one-3E-oxime isomer of formula (IA), the pure d-(17alpha)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yne-3-one-3Z-oxime isomer of formula (IB), which are of gestagen activity, as well as the process for the synthesis of the mixture of the above isomers and the pure isomers. The invention also relates to the pharmaceutical compositions - and the process for their synthesis - which contain either the pure isomer of formula (IA) or the pure isomer of formula (IB) as active ingredient as such or in combination with other active ingredients (for example an oestrogen agent) together with pharmaceutical auxiliary materials commonly used in practice.

专利号:EP-1638988-B1
优先权日:2003-06-30
标题:Process for the synthesis of high purity d-(17alpha)-13-ethyl-17hydroxy-18,19-dinorpre:gn-4-ene-20-yne-3-one-oxime
发明人：TUBA ZOLTAN; MAHO SANDOR; KISS JANOS; MAGYARI ENDRENE; TERDY LASZLO
权利人:RICHTER GEDEON NYRT
摘要:The invention relates to a process for the synthesis of high purity d-(17alpha)-13-ethyl-17­hydroxy-18,19-dinorpregn-4-ene-20-yne-3-one-oxime (further on norelgestromine) via acetylation of d-norgestrel at position 17, oximation of the oxo group at position 3 of the obtained 17-acetoxy derivative, and finally hydrolyzing the acetoxy group at position 17 of the obtained 3-oxime derivative. The process according to our invention is as follows: the starting material, d-(17alpha-17-hydroxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3­one (d-norgestrel) - purity 93-94 % - is acetylated with acetic anhydride in acetic acid, in the presence of zinc chloride and hydrogen chloride, or 70 % perchloric acid in an inert gas atmosphere, and after completion of the reaction the excess of acetic anhydride and the 'enol acetate' by-product are decomposed with aqueous hydrochioric acid, then the formed d-(17alpha)-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one is isolated from the reaction mixture by addition of ice-water, the precipitated product is filtered off, washed with water, dried, dissolved in dichloromethane or acetone and clarified with silica gel or aluminum oxide and charcoal, after filtration of the clarifier the resulted solution is concentrated and the residue is recrystallized, the obtained d-(17alpha)-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one is reacted either with hydroxylammonium acetate or with hydroxylammonium chloride in the presence of sodium acetate, in acetic acid in nitrogen atmosphere under vigorous stirring for about 1 hour, after completion of the reaction water is added, the precipitated product is filtered off, washed with water, dried and recrystallized, the obtained d-(17alpha-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one-oxime is hydrolyzed with an equivalent amount of an alkali metal hydroxide in a C1-C4 alkanol solution, in nitrogen atmosphere between a temperature of about 5-38 °C, under vigorous stirring, after completion of the reaction the mixture is diluted with water and the pH of the resulted suspension is adjusted to 7,5-9 with acetic acid, the precipitated product is filtered off, washed with water, dried, the crude product is dissolved in ethanol, clarified with charcoal, and after filtration of the clarifier water is added to the obtained solution, the precipitated high purity d-(17alpha)-17-acetoxy-13-ethyl-18,19-dinorpregn-4-ene-20-yne-3-one-oxime is filtered off, washed with water and in given case recrystallized from ethanol.

专利号:US-7816546-B2
优先权日:2003-06-30
标 题:Process for the synthesis of high purity d-(17α)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yn-3-one-oxime
发明人：TUBA ZOLTAN; MAHO SANDOR; KISS JANOS; MAGYARI ENDRENE; TERDY LASZLO
权利人:RICHTER GEDEON VEGYESZET
摘要:The invention relates to a process for the synthesis of d-(17α)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yn-3-one-oxime (also known as norelgestromin) via acetylation of d-norgestrel at position 17; oximation of the oxo group at position 3 of the obtained d-(17α)-13-ethyl-17-(acetyloxy)-18,19-dinorpregn-4-ene-20-yn-3-one; and then hydrolyzing the acetyloxy group at position 17 of the obtained d-(17α)-13-ethyl-17-(acetyloxy)-18,19-dinorpregn-4-ene-20-yn-3-oxime derivative, thereby obtaining norelgestromin.

专利号:US-10022366-B2
优先权日:2013-04-23
标 题:Extending and maintaining micropore viability of microneedle treated skin with lipid biosynthesis inhibitors for sustained drug delivery
发明人：STINCHCOMB AUDRA L; GHOSH PRIYANKA
权利人:STINCHCOMB AUDRA L; GHOSH PRIYANKA; UNIV MARYLAND; UNIV KENTUCKY RES FOUND
摘要:Microneedles and their use as a physical skin permeation enhancement technique facilitate drug delivery across the skin in therapeutically relevant concentrations. Micropores created in the skin by MNs reseal because of normal healing processes of the skin, thus limiting the duration of the drug delivery window. Pore lifetime enhancement strategies can increase effectiveness of MNs as a drug delivery mechanism by prolonging the delivery window. Fluvastatin (FLU) was used to enhance pore lifetime by inhibiting the synthesis of cholesterol, a major component of the stratum corneum lipids. The skin recovered within a 30-45-min time period following the removal of occlusion, and there was no significant irritation observed due to the treatment compared to the control sites. Thus, it can be concluded that localized skin treatment with FLU can be used to extend micropore lifetime and deliver drugs for up to 7 days across MN-treated skin.

专利号:US-2005032763-A1
优先权日:2003-06-30
标题:Process for the synthesis of high purity D-(17a)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yn-3-one oxime

专利号:EP-1641812-A1
优先权日:2003-06-30
标 题 :PURE D-(17a)-13-ETHYL-17-HYDROXY-18,19-DINORPREGN-4-ENE-20-YNE-3-ONE-3E- AND -3Z-OXIME ISOMERS, AS WELL AS PROCESS FOR THE SYNTHESIS OF THE MIXTURE OF ISOMERS AND THE PURE ISOMERS