54201-83-1Relevant articles and documents
Environmentally-friendly synthesis method of ulipristal acetate intermediate and ulipristal acetate
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, (2020/07/14)
The invention provides a method for environmentally-friendly synthesis of an ulipristal acetate intermediate and ulipristal acetate. According to the invention, a compound 2 is used as a starting rawmaterial, and reacts with acetylene in a solvent to form an alkynyl alcohol compound intermediate 3, a hydration reaction is performed with water under the catalysis of an ionic liquid and CO2 to obtain an intermediate 4, the intermediate 4 is subjected to carbonyl protection to obtain an intermediate 5, and the intermediate 5 is subjected to double bond epoxidation, a Grignard reaction, decarbonylation protection and acetylation to obtain the high-purity ulipristal acetate. The method is environment-friendly, convenient in steps, mild in conditions, low in cost, easy to amplify and suitable for industrial production, and the solvent can be recycled.
Synthetic method of norgestomet
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Paragraph 0074; 0078-0081; 0093-0094, (2019/04/17)
The invention relates to a synthetic method of norgestomet. The synthetic method includes the following steps: subjecting a compound II and a peroxide to an epoxidation reaction to obtain a compound III; subjecting the compound III and a Grignard reagent to 1,4 addition reaction under the action of a copper salt catalyst to obtain a compound IV; putting the compound IV and acid into an organic solvent to remove protecting groups and hydroxyl groups to obtain a compound V; subjecting the compound V and alkali metal to a Birch reduction reaction in a liquid ammonia solvent to obtain a compound VI; subjecting the compound VI and the acid to a double bond isomerization reaction in the organic solvent to obtain a compound VII; subjecting the compound VII and an acetylating reagent to an esterification reaction under base catalysis to obtain a compound I, namely the norgestomet. The synthetic method has the advantages that the synthetic method has a short route, and the costs of starting materials and other reagents used are low; purification in the synthesis method is convenient, no column chromatography separation and purification is required, the yield and purity of the prepared norgestomet product are high, and the norgestomet is suitable for industrial production.
Cyclic utilization method of sterides epoxy isomer
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, (2018/06/04)
The invention provides a cyclic utilization method of sterides epoxy isomer. Biphenyl organic solvent is reacted with active metal lithium, sodium, and potassium, and others, and reduced to be conjugated double bond; under the alkali environment, the ketal protection radical group is not influenced, and 17- hydroxyl is also not influenced, thus the position of double bond is not changed and doublebonds are directly transformed to be raw material of the last step, and the raw materials are recycled. The method adopts one-step reduction, and solves the existing common technique of opening loopof epoxy bond firstly and then dewatering to be double bonds, and avoids that the ketal protection radical can be damaged by directly reducing epoxy bond to be double bonds by metal in the alkali environment; the epoxy isomer beta and a part of alpha isomer are directly reduced to be the raw material containing conjugated double bond in last step, thus a simple cycle is realized.
17-Alpha-substituted-11-beta-substituted-4-aryl and 21-substituted 19-norpregnadienediones as antiprogestational agents
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, (2016/09/12)
The invention provides 17-alpha-substituted-11-beta-substituted-4-aryl and 21-substituted 19-norpregnadienediones as antiprogestational agents.
Ulipristal acetate impurities and preparation and detection method thereof
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Paragraph 0111, (2017/03/08)
The invention provides ulipristal acetate impurity compounds and a preparation method thereof, and particularly provides a novel compound impurity F (a compound F) and a novel compound impurity K (a compound K). The invention further provides a detection method of the impurities and application of the impurities on quality analysis of an ulipristal acetate bulk drug and a preparation thereof.
Method for preparing ulipristal acetate and key intermediate thereof
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, (2014/10/16)
A method as well as new intermediates for preparing Ulipristal acetate (a compound I) and a method for preparing the new intermediates are provided. The intermediate in a constitutional formula IV is conductive to reacting with methyl lithium or methyl Grignard reagent, a protective group is easy to be removed after a reaction, side reactions are few, a mid-term treatment is simple, the reagents used are cheap, costs are low and a yield is high, if a compound in a constitutional formula V is obtained by the reaction of a compound in a constitutional formula III and the intermediate in the constitutional formula IV, the yield of a two-step reaction is 75%, a purity is above 98%. wherein R is defined in the specification.
ULIPRISTAL ACETATE PREPARATION METHOD AND INTERMEDIATE THEREOF
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Paragraph 0042, (2014/09/29)
A method as well as new intermediates for preparing Ulipristal acetate (a compound I) and a method for preparing the new intermediates are provided. The intermediate in a constitutional formula IV is conductive to reacting with methyl lithium or methyl Grignard reagent, a protective group is easy to be removed after a reaction, side reactions are few, a mid-term treatment is simple, the reagents used are cheap, costs are low and the yield is high, if a compound in a constitutional formula V is obtained by the reaction of a compound in a constitutional formula III and the intermediate in the constitutional formula IV, the yield of a two-step reaction is 75%, a purity is above 98%. wherein R is defined in the specification.
INDUSTRIAL PROCESS FOR THE SYNTHESIS OF 17α-ACETOXY-11β-[4-(N,N-DIMETHYL-AMINO)- PHENYL]-19-NORPREGNA-4,9-DIENE-3,20-DIONE AND NEW INTERMEDIATES OF THE PROCESS
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Page/Page column 9-10; 13-14, (2008/06/13)
The present invention relates to a new industrial process for the synthesis of solvate- free 17α-acetoxy-11β-[4-(N,N-dimethyl-amino)-phenyl]-19-norpregna-4,9-diene-3,20-dione [CDB -2914] of formula (I) which is a strong antiprogestogene and antiglucocorticoid agent. The invention also relates to compounds of formula (VII) and (VIII) used as intermediates in the process. The process according to the invention is the following: i) 3-(ethylene-dioxy)-estra-5(10),9(11)-diene-17-one of formula (X) is reacted with potassium acetilyde formed in situ in dry tetrahydrofuran by known method, ii) the obtained 3-(ethylene-dioxy)-17α-ethynyl-17β-hydroxy-estra-5(10),9(11)-diene of formula (IX) is reacted with phenylsulfenyl chloride in dichloromethane in the presence of triethylamine and acetic acid, iii) the obtained isomeric mixture of 3-(ethylene-dioxy)-21-(phenyl-sulfinyl)-19-norpregna-5(10),9(11),17(20),20-tetraene of formula (VIII) is reacted first with sodium methoxide in methanol, then with trimethyl phosphite, iv) the obtained 3-(ethylene-dioxy)-17α-hydroxy-20-methoxy-19-norpregna-5(10),9(11),20-triene of formula (VII) is reacted with hydrogen chloride in methanol, then v) the obtained 3-(ethylene-dioxy)-17α-hydroxy-19-norpregna-5(10),9(11l)-diene-20- one of formula (VI) is reacted with ethylene glycol hi dichloromethane in the presence of trimethyl orthoformate and p-toluenesulfonic acid by known method, vi) the obtained 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-19-norpregna- 5(10),9(11)-diene of formula (V) is reacted with hydrogen peroxide in a mixture of pyridine and dichloromethane in the presence of hexachloroacetone by known method, vii) the obtained 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-5,10-epoxy-19-norpregn-9(11)-ene of formula (IV), containing approximately a 1:1 mixture of 5α,10α- and 5β,10β-epoxides, is isolated from the solution and reacted with a Grignard reagent obtained from 4-bromo-N,N-dimethyl-aniline in tetrahydrofuran in the presence of copper(I) chloride catalyst without separation of the isomers by known method, viii) the obtained 3,3,20,20-bis(ethylene-dioxy)-5α,17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl]-19-norpregn-9(11)-ene of formula (III) is reacted with potassium hydrogensulfate in water by known method, ix) the obtained 11β-[4-(N,N-dimethylamino)-phenyl]-17α-hydroxy-19-norpregn-4,9-diene-3,20-dione of formula (II) is acetylated with acetic anhydride in the presence of perchloric acid by known method, finally x) the solvate-free compound of formula (I) is liberated from the obtained solvate containing compound of formula (I) in a 1 : 1 mixture of ethanol and water at 70° C.
A practical large-scale synthesis of 17α-acetoxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914)
Rao, Pemmaraju N.,Acosta, C. Kirk,Bahr, Martin L.,Burdett, James E.,Cessac, James W.,Morrison, Paul A.,Kim, Hyun K.
, p. 395 - 400 (2007/10/03)
A new practical synthesis of 17α-acetoxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914) is described. The synthesis gives easily isolable solids at all steps and is amenable to large-scale process. Copyright (C) 2000 Elsevier Science Inc.
Synthesis of N-desmethyl derivatives of 17α-acetoxy-11β(4-N,N- dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione and mifepristone: Substrates for the synthesis of radioligands
Rao, Pemmaraju N.,Acosta, C. Kirk,Cessac, James W.,Bahr, Martin L.,Kim, Hyun K.
, p. 205 - 212 (2007/10/03)
The syntheses of N-desmethyl derivatives of CDB-2914 and the mono-N- desmethyl derivative of Mifepristone are described. We also describe the use of the mono-desmethyl derivatives as substrates for the synthesis of N- tritomethyl derivatives of CDB-2914 a
