- One-pot preparation method for ulipristal acetate
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The invention discloses a one-pot preparation method for ulipristal acetate, belonging to the technical field of drug synthesis. The method comprises the following steps: with a Grignard's substance CW-b as a raw material, performing acidolysis via an org
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Paragraph 0045; 0046-0054
(2019/10/04)
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- Synthesis method of ulipristal acetate
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The invention discloses a synthesis method of ulipristal acetate. The synthesis method comprises the following steps: 1), producing a compound VI from gestadienol under the action of ethylene glycol,p-toluenesulfonic acid and trimethyl orthoformate; 2), oxidizing the compound VI by using hydrogen peroxide to obtain a compound VII; 3), preforming a reaction on the compound VII and a 4-(N, N-dimethylamino) phenylmagnesium bromide Grignard reagent to obtain a compound VIII; 4), hydrolyzing a compound VIII to obtain a compound XI; 5), preforming a reaction on the compound XI, glacial acetic acidand acetic anhydride under the catalytic action of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 4-dimethylaminopyridine and iron perchlorate to obtain the ulipristal acetate. In the synthesis method, reaction conditions for obtaining the ulipristal acetate from ulipristal are relatively mild, demethylated ulipristal or ulipristal oxynitride is unlikely to produce, and the production process is more controllable.
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- Acetic acid wu lisi he and its intermediate preparation method
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The invention discloses a preparation method of ulipristal acetate and an intermediate thereof, and belongs to the field of pharmaceutical synthesis. The preparation method of the ulipristal acetate comprises the following steps: by taking 3,3-(ethylenedioxy)-19-methylestra-5(10),9(11)-diene-3,17-diketone as raw material, enabling the raw material to react with sodium acetylide or potassium acetylide to obtain a compound III, carrying out high-selectivity epoxidation by oxide to obtain a compound IV, subsequently enabling the compound IV to react with 4-(N,N-dimethyl amino) phenyl magnesium bromide Grignard reagent to obtain a compound V, then enabling the compound V to react with phenyl sulfonic acid chloride to obtain a compound VI, enabling the compound VI to respectively react with sodium methoxide and trimethyl phosphate to obtain a compound VII, hydrolyzing and removing a protection group to obtain a compound VIII, finally carrying out acetylation reaction to obtain the ulipristal acetate, wherein the reaction formulae are as shown in the description. The method is short in synthetic route, mild in reaction conditions, high in yield and purity of products, low in cost, stable and controllable in quality, and is suitable for industrial production.
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- Impurity of ulipristal acetate and preparation and detecting method of impurity
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The invention provides an impurity compound of ulipristal acetate and a preparation method of the impurity compound, particularly provides a new compound impurity B (compound B) and an impurity C (compound C), and further provides a detecting method of the impurities and application of the impurities to quality analysis of ulipristal acetate crude drugs and preparations of the ulipristal acetate crude drugs.
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- Ulipristal acetate impurities and preparation and detection method thereof
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The invention provides ulipristal acetate impurity compounds and a preparation method thereof, and particularly provides novel compound impurities including A (a compound A), G (a compound G), H (a compound H) and J (a compound J). 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.
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- First synthesis and characterization for the stereoisomers of Ulipristal acetate
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The three stereoisomers, 11α,17α-isomer I, 11α,17β-isomer II and 11β,17β-isomer III are related substances of the selective progesterone receptor modulator Ulipristal acetate. Herein, we presented an efficient and practical synthesis approach to deliver t
- Zhao, Yi,Li, Xiaolong,Liu, Hong,Yu, Yongguo,Hai, Li,Guo, Li,Wu, Yong
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- INDUSTRIAL PROCESS FOR THE SYNTHESIS OF ULIPRISTAL ACETATE AND ITS 4'-ACETYL ANALOGUE
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The present invention relates to a new process for the synthesis of compounds of formula (I) (wherein the meaning of R is dimethylamino or acetyl group) using the compound of formula (II) (wherein the meaning of R is dimethylamino or 2-methyl-1,3-dioxolan-2-yl group) as starting material, as well as to the intermediate of the process.
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- Method for preparing ulipristal acetate and key intermediate thereof
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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.
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- NOVEL PROCESS AND INTERMEDIATE FOR PREPARATION OF ULIPRISTAL
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The present invention is related to a novel process for the preparation of ulipristal (I) that comprises reaction of 17-α-ethynyl-17-β-hydroxy-11-β-(4-N,N-dimethylamino phenyl)- 9-norpregna-4,9-diene-3-one (III) with phenyl sulphenyl chloride (IVa) or p-nitro phenyl sulphenyl chloride (IVb) in the presence of organic base and solvent to give sulfoxide (Va) or (Vb) respectively. Sulfoxides (Va) or (Vb) are reacted with alkali metal alkoxide in alcoholic solvent followed by treatment with aqueous acid. The present invention also relates to novel intermediate 11-β-(4-N,N-dimethylaminophenyl)-21(p- nitro-phenyl-sulphinyl)-19-norpregna-4(5), 9(10), 17(20) 20-tetraene, 3-one (Vb).
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- ULIPRISTAL ACETATE PREPARATION METHOD AND INTERMEDIATE THEREOF
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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.
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- A simple and convenient synthetic route to Ulipristal acetate
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We set out to describe a new and efficient route for preparing Ulipristal acetate with a good yield. The selected epoxidization conditions gave out 80% of 5α,10α-epoxide 2a in the two diastereoisomers which greatly improved the yield of 11β-substituted isomer 4a. And phenyl-sulfinyl compound 6 was synthesized from ketone 5 directly treated with phenylsulfenyl chloride in the presence of triethylamine. These synthetic procedures is only 8 steps, less than currently reported in the literature, but more suitable for industrial process.
- Yu, Yongguo,He, Yun,Zhao, Yi,Hai, Li,Wu, Yong
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p. 1293 - 1297
(2013/11/06)
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- A practical large-scale synthesis of 17α-acetoxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914)
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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.
- Rao, Pemmaraju N.,Acosta, C. Kirk,Bahr, Martin L.,Burdett, James E.,Cessac, James W.,Morrison, Paul A.,Kim, Hyun K.
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p. 395 - 400
(2007/10/03)
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- 11 β-substituted progesterone analogs
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A 11β-aryl-19-norprogesterone steroid of the formula: STR1 wherein (i) R1 is H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, OH, OC(O)CH3, or OC(O)R5, wherein R5 is C2-8 alkyl, C2-8 alkenyl, C2-8 alkynyl or aryl, R2 is H, R3 is H, C1-4 alkyl, C2-4 alkenyl or C2-4 alkynyl, R4 is H, CH3, F or Cl, R6 is H, (CH3)2 N, CH3 O, CH3 CO, CH3 S, CH3 SO, CH3 SO2, and X is O or NOCH3 ; or (ii) R1 and R2 taken together are a carbon-carbon bond and R3, R4, R6 and X are as defined above; or (iii) R1 and R3 taken together are --CH2 -- or --N=N--CH2 --, R2 is H and R4, R6 and X are as defined above; or (iv) R2 and R3 taken together are =CH2 and R1, R4, R6 and X are as defined above.
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