- Impurity control method of fulvestrant
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The invention belongs to the field of pharmaceutical chemicals, and relates to a fulvestrant impurity control method, which is characterized in that from the introduction of chiral carbon to the synthesis of a fulvestrant intermediate compound represented by a formula VII-1, multi-step and step-by-step control is performed on 7beta isomer impurities, so that the 7beta isomer content of the VII-1 compound is between 0.1% and 0.3%, and finally the qualified fulvestrant bulk drug with stable quality is prepared. The impurity control method is simple to operate, low in production cost and high intotal yield, and can be applied to large-scale industrial production.
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- Processes and intermediates for preparing fulvestrant
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The present invention provides a method and an intermediate for preparing fulvestrant, and relates to a method for preparing fulvestrant, and an intermediate (5) of fulvestrant, and a synthetic methodthereof. The method provided by the invention can be used for obtaining high-purity fulvestrant, and is suitable for industrial mass production.
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Paragraph 0068-0071
(2020/05/30)
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- Fulvestrant preparation method
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The invention provides a new fulvestrant synthesis method, which has characteristics of mild reaction condition, simple route and high yield and high purity of each reaction intermediate, can obtain high-purity fulvestrant through re-crystallization without column chromatography, and is suitable for industrial production. The specific technical scheme of the present invention comprises that a compound represented by a formula I and a reagent are subjected to a halogenation reaction in a solvent to generate a compound represented by a formula II; the compound represented by the formula II and thiourea are subjected to a reflux reaction in a solvent to generate a compound represented by a formula III; the compound represented by the formula III and a compound represented by a formula IV aresubjected to a nucleophilic substitution reaction and a hydrolysis reaction in an alkali solution and an organic solvent to generate a compound represented by a formula V; and the compound representedby the formula V is oxidized with an acetic acid hydrogen peroxide oxidation system in a solvent to obtain fulvestrant.
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- Fulvestrant intermediate
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The present invention provides a new fulvestrant intermediate compound represented by a formula III, wherein the mass spectrum of the intermediate III is [M+H]237.2082. According to the present invention, with the application of the intermediate to prepare fulvestrant, the route is simple, the yield and the purity of each reaction intermediate are high, the high-purity fulvestrant can be obtained through re-crystallization without column chromatography, and the method is suitable for industrial production.
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- Improved method for recovering fulvestrant with unqualified isomer ratio
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The invention relates to an improved method for recovering fulvestrant with an unqualified isomer ratio. A halide is adopted as a reduction catalyst for replacing reductants with potential safety hazard and environmental pollution in the prior art, so that the discharge of three wastes (waste gas, waste water and industrial residue) is reduced, the recovery rate of the fulvestrant is greatly improved, the recovery rate of the unqualified fulvestrant can reach about 70%, and thus the improved method is beneficial for industrial popularization.
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Paragraph 0011; 0013
(2018/04/02)
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- A new method for the synthesis of fulvestrant (by machine translation)
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The invention discloses a new method for the synthesis of fulvestrant, it is in order to intermediate X and five fluorine amyl alcohols as the starting material as the starting material, obtained through the four-step reaction of fulvestrant, this line does not need to column chromatography purification, the crude final product only needs to re-crystallization can be obtained the fulvestrant accord with Pharmacopoeia standards, overall yield is 50 the [...] 60%, and the raw material are industrial product, is easy to obtain, the quality is easy to control. (by machine translation)
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Paragraph 0061-0064
(2018/02/04)
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- PROCESS FOR THE PREPARATION OF FULVESTRANT
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The present invention relates to an improved process for the preparation of Fulvestrant (I). Also, provided is novel intermediate of Fulvestrant and a process for the preparation of the same.
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- PROCESS AND INTERMEDIADES FOR THE PREPARATION OF 7-ALKYLATED STEROIDS
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A process for preparing compounds of formula (I), or a salt, solvate or stereoisomer thereof, including Fulvestrant, which process comprises free radical to a compound of formula (III), or a salt, solvate or stereoisomer thereof. The invention also refers to intermediates of said process.
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- An alternative synthesis of the breast cancer drug fulvestrant (Faslodex): catalyst control over C-C bond formation
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Fulvestrant (Faslodex) was synthesized in four steps (35% overall yield) from 6-dehydronandrolone acetate. Catalyst controlled, room temperature, diastereoselective 1,6-addition of the zirconocene derived from commercially available 9-bromonon-1-ene was used in the key C-C bond forming step.
- Caprioglio, Diego,Fletcher, Stephen P.
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p. 14866 - 14868
(2015/10/06)
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- PROCESS FOR PREPARING 7-ALPHA-[9-(4,4,5,5,5-PENTAFLUOROTHIOPENTYL) NONYL]ESTRA-1,3,5(10)-TRIENE-3,17-BETA-DIOL
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A process is described for the industrial scale preparation of 7a-[9-(4,4,5,5,5- 5 pentafluorothiopentyI)nonyl]estra-1,3,5(10)-triene-3,17?-diol, a precursor of steroids with hormonal activity which include Fulvestrant.
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- Fulvestrant: From the laboratory to commercial-scale manufacture
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The development of a commercial manufacturing process for fulvestrant (the active ingredient in 'Faslodex') is described. Key steps in the synthesis are stereoselective 1,6-addition of an organocuprate to a steroidal dienone followed by copper-mediated aromatisation of the A-ring. The strategy for dealing with noncrystalline intermediates is outlined. The production of drug substance of acceptable quality is critically dependent on limiting the formation of key impurities. The origin of these impurities is discussed, and measures to prevent or control their formation are described.
- Brazier, Eve J.,Hogan, Philip J.,Leung, Chiu W.,O'Kearney-McMullan, Anne,Norton, Alison K.,Powell, Lyn,Robinson, Graham E.,Williams, Emyr G.
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experimental part
p. 544 - 552
(2011/07/30)
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- Process for the manufacture of 7-alpha-[9-(4,4,5,5,5-penta fluoropentylsulphinyl) nonyl]estra-1,3,5-(10)- triene-3,17-beta-diol
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The present invention provides a novel multi-step process for the manufacturing Fulvestrant, which is economical and convenient to operate at commercial scale, and requires only simple chromatographic separations after the coupling step of adding the side chain to the 7 position of the steroid.
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Page/Page column 4
(2010/07/10)
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- PROCESS FOR THE MANUFACTURE OF 7-ALPHA-[9-(4,4,5,5,5-PENTA FLUOROPENTVLSULPHINVL) NONVLLESTRA-L,3,5-(10)- TRIENE-3,17-BETA-DIOL
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The present invention provides a novel multi-step process for the manufacturing Fulvestrant, which is economical and convenient to operate at commercial scale, and requires only simple chromatographic separations after the coupling step of adding the side chain to the 7 position of the steroid.
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Page/Page column 6-7
(2009/05/29)
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- Process for the preparation of 7alpha-alkylated 19-norsteroids
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Processes useful in the preparation of pharmaceutical compounds such as fulvestrant and processes for the preparation of fulvestrant.
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Page/Page column 26
(2008/06/13)
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