- Improved procedure for preparation of abiraterone acetate
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An improved procedure for the preparation of abiraterone acetate is described. The present process highlights reduced reaction time, isolation with acid-base treatment without involving column chromatography, multiple crystallization and is amenable to la
- Madhra, Mukesh Kumar,Sriram, Hari Mohan,Inamdar, Murad,Sharma, Mukesh Kumar,Prasad, Mohan,Joseph, Sony
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Read Online
- Synthesis of the anti-prostate cancer drug abiraterone acetate
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Abiraterone acetate is used for the treatment of castration-resistant prostate cancer. Abiraterone acetate was synthesized from dehydroepiandrosterone via a three-step reaction including the formation of tosylhydrazone, cross-coupling reaction and acetylation, and a two-step purification including column chromatography and recrystallization with an overall yield of 51.9%. Here, an improved procedure for the preparation of abiraterone acetate is described. This synthetic process is of easy operation and low cost, which is suitable for industrialization.
- Ma, Siyue,Li, Jianheng,Tang, Huayang,Xu, Feng
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Read Online
- Application of trifluoromethanesulfonate in preparation of abiraterone acetate and synthesis method of trifluoromethanesulfonate
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The invention particularly relates to application of trifluoromethanesulfonate in preparation of abiraterone acetate and a synthesis method. The invention provides a novel method for synthesizing abiraterone acetate. According to the method, a trifluoromethanesulfonate, such as iron trifluoromethanesulfonate and scandium trifluoromethanesulfonate, is adopted as a catalyst, isopropenyl acetate is adopted as an acylation reagent, and acetylation is carried out on the 3-site hydroxyl of abiraterone to synthesize abiraterone acetate. The method is simple to operate and high in product yield, and the use of irritant acetylation reagents such as acetic anhydride and acetyl chloride and chemical amounts of basic groups such as pyridine and triethylamine is avoided.
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Paragraph 0036-0045
(2021/06/12)
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- Slow-, tight-binding inhibition of CYP17A1 by abiraterone redefines its kinetic selectivity and dosing regimen
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Substantial evidence underscores the clinical efficacy of inhibiting CYP17A1-mediated androgen biosynthesis by abiraterone for treatment of prostate oncology. Previous structural analysis and in vitro assays revealed inconsistencies surrounding the nature and potency of CYP17A1 inhibition by abiraterone. Here, we establish that abiraterone is a slow-, tight-binding inhibitor of CYP17A1, with initial weak binding preceding the subsequent slow isomerization to a high-affinity CYP17A1-abiraterone complex. The in vitro inhibition constant of the final high-affinity CYP17A1-abiraterone complex ( ( Ki? = 0.39 nM )yielded a binding free energy of -12.8 kcal/mol that was quantitatively consistent with the in silico prediction of 214.5 kcal/mol. Prolonged suppression of dehydroepiandrosterone (DHEA) concentrations observed in VCaP cells after abiraterone washout corroborated its protracted CYP17A1 engagement. Molecular dynamics simulations illuminated potential structural determinants underlying the rapid reversible binding characterizing the two-step induced-fit model. Given the extended residence time (42 hours) of abiraterone within the CYP17A1 active site, in silico simulations demonstrated sustained target engagement even whenmost abiraterone has been eliminated systemically. Subsequent pharmacokineticpharmacodynamic (PK-PD) modeling linking time-dependent CYP17A1 occupancy to in vitro steroidogenic dynamics predicted comparable suppression of downstream DHEA-sulfate at both 1000- and 500-mg doses of abiraterone acetate. This enabled mechanistic rationalization of a clinically reported PK-PD disconnect, inwhich equipotent reduction of downstreamplasma DHEAsulfate levels was achieved despite a lower systemic exposure of abiraterone. Our novel findings provide the impetus for reevaluating the current dosing paradigmof abiraterone with the aim of preserving PD efficacy while mitigating its dose-dependent adverse effects and financial burden. SIGNIFICANCE STATEMENT With the advent of novel molecularly targeted anticancer modalities, it is becoming increasingly evident that optimal dose selection must necessarily be predicated on mechanistic characterization of the relationships between target exposure, drug-target interactions, and pharmacodynamic endpoints. Nevertheless, efficacy has always been perceived as being exclusively synonymous with affinity-based measurements of drug-target binding. This work demonstrates how elucidating the slow-, tight-binding inhibition of CYP17A1 by abiraterone via in vitro and in silico analyses was pivotal in establishing the role of kinetic selectivity in mediating time-dependent CYP17A1 engagement and eventually downstream efficacy outcomes.
- Cheong, Eleanor Jing Yi,Nair, Pramod C.,Neo, Rebecca Wan Yi,Tu, Ho Thanh,Lin, Fu,Chiong, Edmund,Esuvaranathan, Kesavan,Fan, Hao,Szmulewitz, Russell Z.,Peer, Cody J.,Figg, William D.,Chai, Christina Li Lin,Miners, John O.,Chan, Eric Chun Yong
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p. 438 - 451
(2020/09/04)
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- Synthetic method of abiraterone acetate and intermediate thereof (by machine translation)
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The invention relates to a synthesis method of abiraterone acetate and a dragon intermediate thereof. In the synthesis method of abiraterone acetate intermediate, a compound of formula (I), a chloro reagent and a base are chlorinated to obtain the abiraterone acetate intermediate of formula (II). The mass ratio of the compound of the formula (I) to the base is 1: (1.5 -3). The structure of the compound of formula (I) and abiraterone acetate is as follows. To the synthesis method, the occurrence probability of side reactions in the chlorination reaction process can be reduced while the high reaction activity is maintained, so that the yield and purity of the abiraterone acetate intermediate can be improved, and the process is simple. (by machine translation)
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- Method for preparing abiraterone acetate
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The invention provides a method for preparing abiraterone acetate. Specifically, the invention relates to an improved method for synthesizing abiraterone or a derivative thereof through a key 3 beta-benzoyloxy intermediate. According to the process, intermediate DHEA 3-benzoyloxy ester is a solid, the intermediate with higher purity can be obtained through a crystallization method, and the processoperability is high. Meanwhile, benzoyl is strong in electric negative force, easy to react with hydroxyl and high in acylation rate, and a six-membered ring structure is twisted in a space structureof a benzoyl functional group, so that elimination reaction is not easy to perform, and generation of process byproducts is effectively avoided.
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- Abiraterone acetate preparation method
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The invention provides an abiraterone acetate preparation method, which comprises: dissolving 17-iodoandrosta-5,16-dien-3 beta-hydroxyl and 3-pyridine zinc neopentanoate in an organic solvent, reacting at 50-80 DEG C for 3-12 h under the catalysis of a palladium catalyst, removing the solvent after the reaction is finished, and esterifying with acetic anhydride to obtain an abiraterone acetate product. According to the invention, the method overcomes the defects of expensive raw materials, high cost, harsh reaction conditions and the like in the prior art, is low in cost, mild in preparation conditions, simple and convenient in production method and suitable for industrial production, and has high application value.
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Paragraph 0025-0039
(2020/03/06)
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- Preparation method of abiraterone acetate
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The invention provides a preparation method of abiraterone acetate: dissolving an alkenyl iodide (17-iodoandrostane-5,16-diene-3[beta]-acetate or 17-iodoandrostane-5,16-diene-3[beta]-hydroxyl), a compound (I), an aryl boride (diethyl(3-pyridyl)borane), a compound (II), pyridine-3-boronic acid or pyridine-3-boronic acid pinacol ester, an alkaline substance, and a Pd/C catalyst in an organic solvent, and performing a reaction at 60-120 DEG C for 3-12 h; after the reaction is finished, carrying out post-treatment on the reaction liquid to obtain the abiraterone acetate and recycling the Pd catalyst; wherein the compound (I) and compound (II) are represented as the formulas as follows. The method is high in yield, is less in impurity and has convenience of recycling the noble metal catalyst and obtaining raw materials, is simple in operation, is available to industrial production, and has great application value.
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- A process for the production of acetate (by machine translation)
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The invention belongs to the technical field of pharmaceutical and chemical industries, and in particular relates to a process for the production of acetate, this invention has improved the acetate synthetic route, to the dehydroepiandrosterone as raw materials, by condensation with hydrazine hydrate, iodo, with 3 - pyridine [...] coupled reactions, such as the acetylation 4 step reaction synthesizes the target product acetate, the overall yield is 51.4%. Is determined synthetic compound 17 - (3 - pyridyl) - androst - 5, 16 - diene - 3 β - ol the best reaction time and the reaction temperature is 5 h, 35 °C. The route mild reaction conditions, raw materials are cheap and easy to obtain, and the production cost is low. (by machine translation)
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Paragraph 0035; 0036
(2018/09/08)
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- Abiraterone acetate preparation method
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The invention discloses an abiraterone acetate preparation method, and particularly provides an abiraterone acetate preparation process. In the prior art, the preparation process comprises a palladiumcatalyzed coupling reaction, the palladium catalyzed reaction can cause the pollution on the reaction product, and palladium is difficultly separated from the target product. According to the presentinvention, palladium is removed with the substituted phosphine-containing compound so as to effectively control the palladium residue.
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- Structure-Based Design of Inhibitors with Improved Selectivity for Steroidogenic Cytochrome P450 17A1 over Cytochrome P450 21A2
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Inhibition of androgen biosynthesis is clinically effective for treating androgen-responsive prostate cancer. Abiraterone is a clinical first-in-class inhibitor of cytochrome P450 17A1 (CYP17A1) required for androgen biosynthesis. However, abiraterone also causes hypertension, hypokalemia, and edema, likely due in part to off-target inhibition of another steroidogenic cytochrome P450, CYP21A2. Abiraterone analogs were designed based on structural evidence that B-ring substituents may favorably interact with polar residues in binding CYP17A1 and sterically clash with residues in the CYP21A2 active site. The best analogs increased selectivity of CYP17A1 inhibition up to 84-fold compared with 6.6-fold for abiraterone. Cocrystallization with CYP17A1 validated the intended new contacts with CYP17A1 active site residues. Docking these analogs into CYP21A2 identified steric clashes that likely underlie decreased binding and CYP21A2 inhibition. Overall, these analogs may offer a clinical advantage in the form of reduced side effects.
- Fehl, Charlie,Vogt, Caleb D.,Yadav, Rahul,Li, Kelin,Scott, Emily E.,Aubé, Jeffrey
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p. 4946 - 4960
(2018/06/20)
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- Material used for abiraterone acetate refined products and synthetic method thereof
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The invention belongs to the technical field of organic chemistry, and discloses a material used for abiraterone acetate refined products and a synthetic method thereof. The synthetic method of the material used for abiraterone acetate refined products is realized by reaction of acetate dehydroepiandrosterone, a compound B, a compound C, a compound D and a compound E. According to the invention, the synthetic route is short, reaction conditions are easily achieved, and compared with other synthetic routes, the material has the advantages that weak acid is adopted, corrosion to equipment is small, and single-step yields are all 85% or above.
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- Synthesis method of abiraterone acetate highly finished product
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The invention belongs to the technical field of organic chemistry, and discloses a synthesis method of an abiraterone acetate highly finished product. The synthesis method comprises the following steps: sequentially adding absolute ethyl alcohol, hydrazine hydrate and glacial acetic acid in dehydroisoandrosterone 3-acetate (SM1), and preparing a reactant B at the temperature of 20-30 DEG C; addingtetrahydrofuran and iodine, slowly adding tetramethyl guanidine at the temperature of -5 to 5 DEG C, controlling the temperature to be 10 DEG C or below, and dropwise adding a tetrahydrofuran solution of the compound B at the temperature of -5 to 5 DEG C for 6 h to obtain a compound C; sequentially adding tetrahydrofuran, diethyl-(3-pyridine)borane, trans-dichlorobis(triphenyl-phosphine)palladiumand a tetrabutylammonium fluoride trihydrate in the compound C to obtain a compound D; and adding dichloromethane and 4-dimethylaminopyridine in the compound D, slowly adding acetic anhydride at thetemperature of 15-35 DEG C, and adding activated carbon and methanol-water after finishing the reaction to obtain a compound E, and highly finishing the compound E to prepare the abiraterone acetate highly finished product.
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- Novel method for preparing abiraterone acetate
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The invention relates to the technical field of medicines, and in particular relates to a novel method for preparing abiraterone acetate. The abiraterone acetate prepared according to the preparationmethod provided by the present application has a high yield and is easy to purify compared with the prior art, the method can reduce hydroxyl by-products and double- bond by-products generated duringthe reaction, a content of a single impurity is less than 0.1%, the preparation method is simple, the costs are suitable, raw materials have small toxicity, and the method is suitable for industrialized mass production.
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Paragraph 0085; 0093; 0094; 0207
(2018/10/11)
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- A method for avoiding heavy metal residual acetate preparation method
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The invention discloses a novel method for preparing abiraterone acetate. The method comprises the following steps of: hydroxyl protection, Aldol reaction, dehydration reaction, deprotection and acetylation. According to the method, the heavy-metal reagent, the strict anhydrous and anaerobic equipment and the expensive alkyl boron reagent are not used, thus the cost is reduced greatly. The method is suitable for mass industrial production.
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- Synthesis method of abiraterone acetate
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The invention discloses a synthesis method of abiraterone acetate. The method includes: taking dehydroepiandrosterone as the raw material, conducting condensation with p-toluenesulfonhydrazide, then carrying out coupling reaction with 3-bromopyridine, and conducting acetylation so as to synthesize the target product abiraterone acetate. According to the synthesis method provided by the invention, the route has mild reaction conditions, the raw materials are cheap and easily available, and the production cost is low.
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Paragraph 0027; 0028; 0035; 0036; 0043; 0044
(2017/09/02)
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- A new method for synthesizing acetate (by machine translation)
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The invention relates to a new method for synthesizing acetate, which belongs to the field of drug synthesis, more specifically, relates to the treatment of advanced prostate cancer drug acetate new synthetic method and in the synthetic method relates to new intermediates for the preparation of compounds. This invention adopts the acetic acid pregnancy double-alkene alcohol ketone as raw materials, by methyl R base asia sulphone lithium reagent addition and rearrangement reaction to obtain the catalyst product 3, the catalyst 3 by oxidation and hetero D - A, isomerization, acetylation reaction such as synthesis of the compound of acetate. The invention solves the problems of the prior art synthetic materials of the more expensive the cost problem, provides a high yield, environmental pollution is small, simple and of the purified preparation [...] acetate method, this method is comparatively easy to amplification to the industrial production. (by machine translation)
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Paragraph 0008; 0025
(2017/09/29)
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- A acetate synthesis method
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The invention relates to a synthesis method of abiraterone acetate. According to the synthesis method of the abiraterone acetate, a compound 1 is taken as a revelator, and the abiraterone acetate is prepared through steps such as esterification, Grignard reagent reaction, dehydration, acylation, reduction, acetylation and the like.
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- A method for preparing abiraterone acetate (by machine translation)
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The invention relates to a method for preparing abiraterone acetate, the method is to dehydrogenation epandrosterone as raw materials, with hydrazine hydrate, iodine response, to obtain 17-iodo-androst -5,16-diene -3 β-ol, then the under the catalysis of palladium benzene phosphine base43 with 3-pyridine zinc halide occurs arab League bit dragon Negishi coupling reaction, the final with acetyl chloride or acetic anhydride esterification, to obtain the target product abiraterone acetate. (by machine translation)
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Paragraph 0034; 0035
(2017/02/09)
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- Green Suzuki coupling reaction for synthesis of abiraterone acetate and its analogues
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An eco-friendly efficient method was developed for the synthesis of abiraterone acetate and analogues in water-PEG-400 (6:1; v/v) at 75°C from various arylboronic acids and 17-(trifluoromethanesulfonyl)oxy-3β-acetoxylandrosta-5,16-diene obtained from the 3-acetate of dehydroepiandrosterone.
- Bian, Xiaoqin,Wang, Lizhong,Liu, Jinliang,Wang, Cunde
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p. 289 - 292
(2016/07/06)
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- ALTERING STEROID METABOLISM FOR TREATMENT OF STEROID-DEPENDENT DISEASE
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A method of treating steroid-dependent disease such as prostate cancer in a subject is described that includes administering a therapeutically effective amount a CYP17A inhibitor and an effective amount of a 5- -reductase inhibitor to the subject.
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- A method for synthesizing arab League bit dragon acetate
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The invention discloses a synthetic method of abiraterone acetic ester. The synthetic method is characterized by taking dehydro-epiandrosterone acetic ester shown by a formula (I) as a raw material, and performing reduction, dehydration and Heck coupling reaction to prepare abiraterone acetic ester shown by a formula (II). The synthetic method is easy to operate, is high in total yield and is a new synthesis technical route which is safe, and the raw material is easily-available to facilitate industrial production.
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- INHIBITORS OF CYP17A1
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Compounds according to formula I or II are provided. Such compounds are useful in treating cancers, such as leukemia, colon cancer, breast cancer, or prostate cancer by beneficially inhibiting CYP17A1. Pharmaceutical compositions and methods including the compounds are also provided.
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- Abiraterone acetate and wherein the intermediate preparation method
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The invention relates to a method for preparing abiraterone which is a key intermediate of abiraterone acetate serving as a medicament for treating prostatic cancer and a method for preparing the abiraterone acetate by using the intermediate thereof. The methods are simple in processes, and the products have high purity and low content of impurities.
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- A process for the purification of abiraterone acetate
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The present invention provides a purifying method for abiraterone acetate. According to the method, phosphoric acid is adopted as a salt forming reagent to react with a abiraterone acetate crude product to obtain a light yellow crystal, wherein the light yellow crystal is the abiraterone acetate phosphate, is easily filtered, and has the purity more than 98%, the abiraterone acetate phosphate can be used for the next reaction without further purification to prepare the abiraterone acetate, and the purity of the abiraterone acetate prepared by freeing can be more than 98%; the purification process is simplified, the production cost is reduced, and the method is suitable for industrial production.
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Paragraph 0008; 0026
(2017/02/09)
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- Abiraterone acetate oxalate and method for purification of abiraterone acetate
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The invention relates to an abiraterone acetate oxalate and a purification method of abiraterone acetate. Oxalate and an abiraterone acetate crude product are subjected to a reaction to obtain abiraterone acetate oxalate; and then the abiraterone acetate oxalate is subjected to a dissociation reaction to obtain abiraterone acetate.
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Paragraph 0030; 0033-0034
(2017/04/08)
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- A method for preparing abiraterone acetate
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The invention discloses a preparation method of abiraterone acetate suitable for industrial production. The method is used for preparing abiraterone acetate through acylating, condensing, separating and purifying, wherein the acylating step is realized as follows: with dehydroepiandrosterone acetate as a raw material, adding the dehydroepiandrosterone acetate into methanol and dissolving under stirring, then, adding p-toluene sulfonic acid and a basic catalyst under a low-temperature condition, and reacting under a room temperature condition. The invention provides a novel preparation method of abiraterone acetate. The method can remarkably increase the yield of abiraterone acetate, remarkably improve the quality of abiraterone acetate, reduce the production cost and meet the requirement for large-scale industrial production.
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Paragraph 0045; 0046
(2017/03/14)
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- A acetate preparation method
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The present invention discloses a zytiga synthesis method, which comprises: 1) under the protection of an inert gas, at a room temperature, mixing a palladium catalyst, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl and 3-pyridylboronic acid to obtain a mixture I; 2) under the protection of an inert gas, at a room temperature, mixing a catalyst PTS aqueous solution and a compound 17-iodoandrosta-5,16-dien-3beta-ol acetate under a basic condition to obtain a mixture II, adding the mixture II to the mixture I obtained in the step 1), and carrying out a reaction at a room temperature or under a heating condition to obtain a zytiga crude product; and 3) quenching the reaction with saturated brine, adopting an organic solvent I to extract the water phase, mixing the organic phases, drying, carrying out reduced pressure concentration, and carrying out re-crystallization on the organic solvent II or the mixed solution of the organic solvent II and water to obtain the zytiga fine product.
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Paragraph 0018; 0024; 0025
(2017/02/02)
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- A method for preparing arab League bit Long Yi ester (by machine translation)
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The invention discloses a method for preparing arab League bit Long Yi acid ester, comprising the following steps: acetic acid dehydro epandrosterone and 3-chloropyridine Grignard reagent in diethyl ether as the solvent, generate condensation reaction, after dehydration prepared crude ester arab League bit Long Yi ; arab League bit Long Yi ester crude product in methanol as the solvent, hydrolysis under alkaline conditions, make 17 - (3-pyridyl)-androsta -4,16-diene -3 β-ol; 17 - (3-pyridyl)-androsta -4,16-diene -3 β- mellow heavy crystallization; 17 - (3-pyridyl)-androsta -4,16-diene -3 β-ol arab League bit Long Yi acid ester prepared by reaction with acetyl chloride. The method of the invention has the advantages of simple operation, the raw materials used are cheap and easily obtained, mild reaction conditions, low equipment requirements, high total yield, the used solvent synchronization recovery, and the like, the production cost is low, large-scale production is easy, has significant industrial application value. (by machine translation)
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Paragraph 0048; 0049; 0050
(2016/12/07)
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- Novel preparation method of abiraterone acetate
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The invention relates to an economic and convenient synthesis method of abiraterone acetate and belongs to the field of drug synthesis. The synthesis method comprises that dehydropregnenolone acetate as an initial raw material undergoes a bromination reaction at the alpha site of the carbonyl, the reaction product undergoes a Witting reaction, the reaction product undergoes a deprotection reaction, the reaction product undergoes an oxidation reaction, the reaction product undergoes a hetero-D-A reaction and the reaction product undergoes an isomerization reaction to produce the desired compound abiraterone acetate. The invention provides the novel preparation method of abiraterone acetate. The novel preparation method has a simple synthesis route and a low synthesis cost and is suitable for industrial production.
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Paragraph 0031; 0032; 0033
(2016/10/10)
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- Preparation method of abiraterone acetate
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The invention provides a preparation method of abiraterone acetate. According to the method, firstly an intermediate product, namely coarse abiraterone is purified and refined, then a purified product of abiraterone is acetylated, the abiraterone acetate is directly prepared, accordingly the coarse abiraterone product which is in an off-white color, relatively high in purity and less in impurity is obtained directly, the coarse abiraterone product is further simply crystallized, the abiraterone acetate which is high in purity and meets the medicinal requirement can be obtained, and therefore the step of chromatography or tedious purification of an inorganic salt-precipitated crystal in a traditional method can be avoided. The method has the advantages of being more convenient and faster in operation and purification treatment step, more suitable for industrialized amplification production and the like.
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Paragraph 0012; 0091; 0092; 0093; 0094; 0095; 0096
(2016/10/09)
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- An improved method for synthesizing arab League bitlong Zhi acetic acid
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The invention discloses an improved abiraterone acetate synthesis method. A known synthesis process is improved in the invention, a reaction solvent is changed, an appropriate temperature is selected and the catalyst dosage is reduced, so that the reaction conditions are more mild, the raw material cost is lower, the operation is simpler, the yield is higher, the product is easier to purify and a technical support is provided for industrial production of abiraterone acetate.
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Paragraph 0039; 0040; 0041
(2016/10/08)
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- Method for Preparing Abiraterone Acetate
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A method for preparing abiraterone acetate. The steps are: dehydroepiandrosterone acetate and trifluoromethanesulphonic anhydride undergo a sulfonylation reaction under the catalysis of an organic base to obtain a compound as represented by formula II; the compound is reacted with a 3-pyridine organoboron compound or a 3-pyridine organosilicone compound under the catalysis of Bis(triphenylphosphine) palladium(II) dichloride to obtain a crude abiraterone acetate product; the crude product is recrystallized in a protic or aprotic solvent to obtain an abiraterone acetate crystal; the crystal is further put into a solvent which easily dissolves the crystal and dissolved under heating, and the solution is dropwise added into a solvent which does not easily dissolve the crystal until a solid is precipitated under stirring, such that a micro powder abiraterone acetate is obtained; and the solvent which easily dissolves the crystal is a mixture of any two or more of acetone, ethanol and water, and the solvent which does not easily dissolve the crystal is water. The method has a rational route, a simple and convenient operation, a good product quality, and a high yield. No column chromatography, and salt-formation are required in the entire process to satisfy requirements of industrial scale productions. Furthermore, an abiraterone acetate particle size of about 10 um is obtained.
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Paragraph 0037; 0038
(2016/09/26)
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- PROCESS FOR THE PREPARATION OF ABIRATERONE AND ABIRATERONE ACETATE
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The present invention relates to a novel process for the synthesis of abiraterone, and in particular of abiraterone acetate, compound of formula (I) reported below: N O (I) which has pharmacological activity useful tor slowing down the progression of prostate cancer at an advanced stage. The process is characterised by an intermediate step wherein DHEA-acetate is triflated using Ar-N(OTf)2 as the triflation reagent.
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- PROCESS FOR THE PREPARATION OF ABIRATERONE OR ABIRATERONE ACETATE
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The present invention relates to a novel process for the synthesis of abiraterone and in particular abiraterone acetate, a compound of formula (I) reported below: having pharmacological activity suitable for slowing down the progression of advanced stage prostate cancer. The process is characaterised by the fact that the intermediate triflation step is carried out on prasterone (DHEA) or its 3-acetate using Ar-N(OTf)2 as the triflation reagent, but where Ar is not phenyl, and by the fact that the base used in this step is an alkali metal alcoholate.
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- ACETATIC ABIRATERONE TRIFLUOROACETATE AND PREPARATION METHOD AND APPLICATION OF SAME
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Provided are acetaic abiraterone trifluoroacetate, a preparation method and an application of same. The acetaic abiraterone trifluoroacetate is obtained through a salt-forming reaction between acetaic Abiraterone and trifluoroacetic acid. The acetaic abiraterone trifluoroacetate undergoes self-purification through recrystallization, and dissociation and recrystallization are performed on the purified abiraterone acetate trifluoroacetate, so that the obtained acetaic abiraterone has a high purity, a high yield and stable quality, and is capable of meeting the requirement for mass production of acetaic abiraterone.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF ABIRATERONE ACETATE
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The present invention relates to an improved process for the preparation of abiraterone acetate. More specifically the invention relates to a process for the preparation of abiraterone acetate free from dimer and other impurities.
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- ACETATIC ABIRATERONE TRIFLUOROACETATE AND PREPARATION METHOD AND APPLICATION OF SAME
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Provided are acetaic abiraterone trifluoroacetate, a preparation method and an application of same. The acetaic abiraterone trifluoroacetate is obtained through a salt-forming reaction between acetaic Abiraterone and trifluoroacetic acid. The acetaic abiraterone trifluoroacetate undergoes self-purification through recrystallization, and dissociation and recrystallization are performed on the purified abiraterone acetate trifluoroacetate, so that the obtained acetaic abiraterone has a high purity, a high yield and stable quality, and is capable of meeting the requirement for mass production of acetaic abiraterone.
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Paragraph 0057
(2015/05/26)
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- PROCESS FOR THE PREPARATION OF UNSATURATED TRIFLUOROMETHANESULFONATE STEROID DERIVATIVES
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Disclosed is a method for the conversion of a compound of formula 3 to a compound of formula 4, wherein R is an acetyl group or an alcohol-protecting group. The process involves reacting 3 with a triflating agent in the presence of a nicotinate (3-pyridinecarboxylate) of a C1-C4 alcohol, preferably methyl nicotinate (methyl 3-pyridinecarboxylate) or ethyl nicotinate (ethyl 3-pyridinecarboxylate), to give 4. The method can be conveniently used in a process for the preparation of Abiraterone or Abiraterone acetate.
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Paragraph 0034
(2015/12/05)
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- PROCEDURE FOR THE PREPARATION OF ABIRATERONE ACETATE AND INTERMEDIATES THEREOF
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Disclosed is a process for the preparation of abiraterone and abiraterone acetate with high yields and purity. A key element of the method is the isolation of a crystalline intermediate that makes the process particularly suitable for implementation on an industrial scale.
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- PROCESS FOR THE PREPARATION OF ABIRATERONE AND INTERMEDIATES THEREOF
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The present invention provides intermediates for preparing abiraterone, and processes for preparing abiraterone and intermediates thereof. The intermediates include a compound of formula (IV): wherein R represents a hydroxy-protecting group.
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- SYNTHESIS OF ABIRATERONE AND RELATED COMPOUNDS
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The present invention relates to processes for obtaining abiraterone and derivatives thereof, such as abiraterone acetate, by means of a Suzuki coupling through a steroid borate of general formula (IV) or a C—C coupling through a steroid hydrazone of general formula (II), as well as to intermediates useful in said processes.
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Paragraph 0241; 0242;
(2014/02/15)
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- PROCESS FOR THE PURIFICATION OF ABIRATERONE ACETATE
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The invention relates to a process for the purification of crude abiraterone acetate by treatment with polymer resins in aqueous solvent. The purified product is recovered by simple concentration and filtration.
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- PROCESS FOR PREPARATION OF ABIRATERONE ACETATE
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The present invention relates to improvement in the process of preparation of abiraterone acetate or a pharmaceutically acceptable salt thereof wherein the improvement comprises purifying the crude 3-and-acetoxyandrosta-5,16-diene-17-yl trifluoromethane sulphonate by crystallization from a solvent to obtain acetoxyandrosta-5,16-diene-17-yl trifluoromethane sulphonate as a crystalline solid and converting it to abiraterone acetate or pharmaceutically acceptable salt thereof.
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Page/Page column 17
(2015/01/16)
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- PROCESS FOR MAKING ABIRATERONE-3-ACETATE
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The present invention relates to an improved process for making abiraterone-3-acetate of formula (1) starting from dehydroepiandrosterone-3-acetate (DHEA) of formula (2). In particular, it relates to an improved process of converting the 17- triflate compound of formula (5) into abiraterone-3-acetate (1) in 2- methyl-THF as the solvent and producing a product of high purity via its acid addition salt abiraterone-3-acetate esylate (1A).
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Page/Page column 16
(2014/05/24)
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- PROCESS FOR THE PRODUCTION OF ABIRATERONE-3-ACETATE INVOLVING AN ENOL TRLIFLATION REACTION IN THE PRESENCE OF AN ALKOXY-PYRIDINE COMPOUND
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The present invention relates to a process for making abiraterone-3-acetate of formula (1) starting from dehydroepiandrosterone-3-acetate of formula (2) by converting it into the triflate of formula (5) in an inert solvent in the presence of an alkoxy group-substituted pyridine.
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Page/Page column 11; 12
(2014/06/11)
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- PROCESS FOR ABIRATERONE ACETATE
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The present invention provides a novel process for the preparation of abiraterone. The present invention also provides a novel process for the preparation of abiraterone acetate.
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Page/Page column 6; 7
(2014/07/21)
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- PROCESS FOR THE PREPARATION OF (3β)-17-(3-PYRIDINYL)ANDROSTA-5,16-DIEN-3-YL ACETATE AND POLYMORPH THEREOF
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The present invention relates to a process for the preparation of (3β)-17-(3- pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula- 1. The present invention also relates to a novel polymorph of compound of formula- 1 and process for its preparation.
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Page/Page column 23
(2014/12/12)
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- PROCESS AND INTERMEDIATES FOR THE PREPARATION OF ABIRATERONE ACETATE
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The present invention relates to a process for the synthesis of (3beta)17-(3- pyridinyl)androsta-5,16-dien-3-yl acetate (Abiraterone acetate) represented by the structure of formula (1), and salts thereof, especially salts with pharmaceutically acceptable acids. The present invention further relates to certain intermediates in such processes.
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- SYNTHESIS OF ABIRATERONE AND RELATED COMPOUNDS
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The present invention relates to processesfor obtaining abirateroneand derivatives thereof, such as abiraterone acetate, by means of a Suzuki coupling through a steroid borate of general formula (IV) or a C-C coupling through a steroid hydrazone of general formula (II), as well as to intermediates useful in said processes.
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Page/Page column 39
(2013/03/28)
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