WO2014188445A1 - PROCÉDÉ DE PRÉPARATION DE L'ACÉTATE DE (3β)-17-(3-PYRIDINYL)ANDROSTA-5,16-DIÈNE-3-YLE ET D'UN POLYMORPHE DE CELUI-CI - Google Patents

PROCÉDÉ DE PRÉPARATION DE L'ACÉTATE DE (3β)-17-(3-PYRIDINYL)ANDROSTA-5,16-DIÈNE-3-YLE ET D'UN POLYMORPHE DE CELUI-CI Download PDF

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WO2014188445A1
WO2014188445A1 PCT/IN2014/000267 IN2014000267W WO2014188445A1 WO 2014188445 A1 WO2014188445 A1 WO 2014188445A1 IN 2014000267 W IN2014000267 W IN 2014000267W WO 2014188445 A1 WO2014188445 A1 WO 2014188445A1
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formula
compound
androsta
dien
solvents
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PCT/IN2014/000267
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English (en)
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Srinivasan Thirumalai Rajan
Muppa Kishore Kumar
Nimmala SRINIVAS RAO
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Srinivasan Thirumalai Rajan
Muppa Kishore Kumar
Srinivas Rao Nimmala
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Publication of WO2014188445A1 publication Critical patent/WO2014188445A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
    • C07J13/005—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 16 (17)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton

Definitions

  • the present invention provides a process for the preparation of (3P)-17-(3-pyridinyl) androsta-5, 16-dien-3-yl ac
  • the present invention also provides a novel polymorph of compound of formula- 1 and process for its preparation.
  • (3p)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate is commonly known as Abiraterone acetate. It is a steroid compound which inhibits selectively and efficiently the enzyme 17-a-hydroxylase-C17-20-lyase, which catalyzes the conversion of dehydroepiandrosterone and androstenedione to testosterone. The inhibition of said enzyme causes a strong decrease of testosterone levels in the patient and therefore this drug is used in the treatment of certain hormone-dependent tumors resistant to chemotherapy such as prostate cancer.
  • the first process involves the reaction of dehydroepiandrosterone with hydrazine hydrate and catalytic amount of hydrazine sulfate provides dehydroepiandrosterone- 17- hydrazone, which upon treatment with iodine solution provides 17-iodo-androsta-5,16-dien- 3 ⁇ - ⁇ 1.
  • the second process involves heating a mixture of iodo compound and diethyl (3-pyridyl)borane in presence of bis(triphenylphosphine)palladium(II) chloride, aq.sodium carbonate in tetrahydrofuran under argon atmosphere at 80°C for 4 days.
  • the obtained compound is first crystallized from a mixture of methanol/acetonitrile and then recrystallized from toluene/methanol mixture and provides Abiraterone in only 57% yield.
  • the resulting compound is acetylated by adding acetic anhydride to a suspension of the hydroxy compound in dry pyridine, which takes 24 hrs for completion to provide Abiraterone acetate.
  • US5604213A patent discloses (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate having M.R. 144-145°C. But there is no other physical characteristic data provided for the same in the said patent. We repeated the process disclosed in the said patent and characterized the obtained compound by PXRD and designated it as crystalline form-A.
  • CN102558275A discloses a-crystalline form
  • CN102321142A discloses crystalline form-E
  • CN102336801A discloses crystalline form-I of Abiraterone acetate.
  • the present inventors surprisingly found novel crystalline form of (3 ⁇ )-17-(3- pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1.
  • the first aspect of the present invention is to provide a crystalline form of (3 ⁇ )-17-(3- pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1, which is herein after designated as crystalline form-M.
  • the second aspect of the present invention is to provide an improved process for the preparation of (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1, comprising of;
  • the third aspect of the present invention is to provide a process for the preparation of pure (3p)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1, comprising of;
  • the fourth aspect of the present invention is to provide a process for the preparation of crystalline form-M of (3p)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1.
  • the fifth aspect of the present invention is to provide crystalline form of (3 ⁇ )-17-(3- pyridinyl)androsta-5,16-dien-3-yl acetate hydrochloride salt compound of formula- la, herein after designated as form-S.
  • the sixth aspect of the present invention is to provide a process for the purification of (3p)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1.
  • the main advantage of the present invention is that it avoids the usage of column chromatography technique for the purification of Abiraterone and Abiraterone acetate as well.
  • the crystalline form-M of the present invention is stable and non-hygroscopic in nature, hence it is highly advantageous for formulators.
  • Figure- 1 Illustrates the X-ray powder diffraction pattern of non-micronized crystalline form-M of (3p)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula- 1.
  • Figure-2 Illustrates the X-ray powder diffraction pattern of micronized crystalline form-M of (3 ⁇ )- 17-(3 -pyridinyl) androsta-5 , 16-dien-3 -yl acetate compound of formula- 1.
  • Figure-3 Illustrates the X-ray powder diffraction pattern of crystalline form- A of (3 ⁇ )-17-
  • Figure-4 Illustrates the X-ray powder diffraction pattern of crystalline form-S of (3 ⁇ )-17-(3- pyridinyl)androsta-5,16-dien-3-yl acetate hydrochloride salt compound of formula- la.
  • suitable solvent refers to "hydrocarbon solvents” such as n-pentane, n-hexane, n-heptane, cyclohexane, pet ether, benzene, toluene, xylene and the like; "ether solvents” such as dimethyl ether, diethyl ether, diisopropyl ether, methyl tert-butyl ether, 2-methoxy ethanol, 1,2-dimethoxy ethane, tetrahydrofuran, 1,4-dioxane and the like; "ester solvents” such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, isobutyl acetate, tert-butyl acetate and the like; "polar-aprotic solvents such as dimethylacetamide, dimethylform
  • suitable base refers to "alkali metal carbonates” such as sodium carbonate, potassium carbonate, lithium carbonate, cesium carbonate and the like; "alkali metal bicarbonates” such as sodium bicarbonate, potassium bicarbonate, lithium bicarbonate, cesium bicarbonate and the like; “alkali metal hydroxides” such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like; “alkali metal alkoxides” such as sodium methoxide, sodium ethoxide, sodium tert.butoxide, potassium methoxide, potassium ethoxide, potassium tert.butoxide, lithium tert.butoxide and the like; alkali metal hydrides such as sodium hydride, potassium hydride, lithium hydride and the like; alkali metal amides such as sodium amide, potassium amide, lithium amide and the like; alkali metal salts of acetic acid such as sodium acetate, potassium acetate and the
  • the first aspect of the present invention provides a crystalline form of (3 ⁇ )-17-(3- pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula- 1, characterized by its powder X-ray diffraction pattern having peaks at 4.5, 5.8, 8.6, 9.1, 11.6, 12.0, 14.8, 15.1, 15.9, 16.3, 17.2, 17.8, 18.4, 19.1, 19.3, 21.7, 21.9, 22.4, 23 and 27.5 ⁇ 0.2 degrees of 2-theta.
  • the said crystalline form is herein after designated as crystalline form-M and it is further characterized by its PXRD pattern as illustrated in figure- 1 (non-micronized form) and figure-2 (micronized form).
  • Polymorphs of a pharmaceutical solid may have different physical and solid state chemical (reactivity) properties.
  • the most stable polymorphic form of a drug substance is often used because it has the lowest potential for conversion from one polymorphic form to another.
  • the crystalline form-M of (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula- 1 of the present invention is highly stable and non-hygroscopic in nature.
  • the non-hygroscopic nature of the compound is determined by the method described in European pharmacopeia.
  • the non-hygroscopic nature of crystalline form-M obtained by the process of the present invention is confirmed by the fact that there is no substantial change in the water content even after the compound is placed in a desiccator containing aqueous ammonium chloride solution for a period of 24 hours at 80 ⁇ 2% relative humidity (RH).
  • the water content of crystalline form-M produced according to the present invention is increased by 0.1% in 24 hours, which confirms the non-hygroscopic nature of the compound.
  • the said characteristic nature is always an advantageous property for formulations.
  • the second aspect of the present invention provides an improved process for the preparation of (3p)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1, comprising of;
  • the suitable catalyst is selected from but not limited to Pd(PPh 3 ) 2 Cl 2> Pd(PPh 3 ) 4 , Pd(OAc) 2 , Pd(OH) 2 , Pd 2 (dba) 3 , Pd(dppe) 2 Cl 2 , Pd(dppf)Cl 2 , Pd(dppf)Cl 2 .CH 2 Cl 2 , Pd(dcypp)Cl 2 , Pd(PhCN) 2 Cl 2 and Pd(CH 3 CN) 2 Cl 2 ;
  • the suitable base is selected from hydroxides, alkoxides, carbonates, bicarbonates and acetates of alkali metals or mixtures thereof;
  • the suitable acetylating agent is selected from acetyl chloride, acetic anhydride, acetic acid and the like;
  • the suitable base is selected from inorganic bases, organic bases or their mixtures;
  • the suitable solvent is selected from ether solvents, alcohol solvents, nitrile solvents, ester solvents, hydrocarbon solvents, polar solvents, chloro solvents, ketone solvents, polar-aprotic solvents, acetic acid or mixtures thereof.
  • the acetylation of (3 )-17-(3-pyridinyl)-androsta-5,16-dien-3-ol compound of formula-4 can also be carried out by treating it with acetic acid in presence of a suitable dehydrating agent in a suitable solvent optionally in presence of a suitable base to provide (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula- 1.
  • the suitable dehydrating agent is selected from but not limited to dicyclohexylcarbodiimide, thionyl chloride, phosphoryl chloride, l-ethyl-3-(3- dimethylaminopropyl)carbodiirnide hydrochloride (EDC.HC1) and the like;
  • the suitable solvent is selected from hydrocarbon solvents, ether solvents, ester solvents, chloro solvents, ketone solvents, nitrile solvents, polar-aprotic solvents, alcohol solvents or their mixtures;
  • the suitable base is selected from organic and inorganic bases.
  • a preferred embodiment of the present invention provides a process for the preparation of (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1, comprising of;
  • the third aspect of the present invention provides a process for the preparation of pure (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1, comprising of;
  • step-c) treating the compound of formula- la obtained in step-c) or step-d) with a suitable base in a suitable solvent to provide pure (3p)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1.
  • step-a) & step-b) the suitable catalyst, the suitable acetylating agent, the suitable base and the suitable solvent are same as defined in step-a) & step-b) respectively of the second aspect of the present invention;
  • the suitable HC1 source is selected from ethyl acetate-HCl, isopropyl alcohol-HCl, methanol-HCl, ethanol-HCl, diethyl ether-HCl, aq.HCl, HC1 gas;
  • the suitable base is selected form hydroxides, alkoxides, carbonates and bicarbonates of alkali metals;
  • step-c) step-d) & step-e) the suitable solvent is selected form alcohol solvents, ether solvents, ester solvents, hydrocarbon solvents, polar solvents, nitrile solvents, ketone solvents, polar-aprotic solvents, chloro solvents or their mixtures;
  • the process disclosed in step-a) of the second and third aspects of the present invention can be carried out optionally in presence of a Siliabond metal Scavenger.
  • the "SiliaBond metal Scavenger” is used for removing residual metals from post reactions. The toxic nature of transition metals has led to the reduction of tolerated residual concentration in active pharmaceutical ingredients (APIs) to single digit ppm.
  • the SiliaBond Metal Scavenger used in the present invention is selected from SiliaBond amine, SiliaBond diamine, SiliaBond triaminetetraacetic acid, SiliaBond thiol, SiliaBond thiourea, SiliaBond propyl bromide and SiliaBond dimercaptotriazine.
  • Thiophenol resin can also be used as a metal scavenger for the said reaction.
  • the compound of formula-4 is obtained in about 85-90% of the yield with 98-99% of purity by HPLC.
  • a preferred embodiment of the present invention provides a process for the preparation of (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula- 1, comprising of;
  • the iodo intermediate compound of formula-2 utilized in the present invention can be synthesized by any of the processes known in the art, for example as described in US5618807A.
  • the (3P)-17-iodo-androsta-5,16-dien-3-ol compound of formula-2 can be synthesized as follows;
  • dehydroepiandrosterone- 17-hydrazone represented by the following formula
  • the suitable proton donor is selected from hydrazine sulfate, sulfuric acid, acetic acid and the like;
  • the suitable base is selected from organic or inorganic base, preferably tetraalkylguanidines;
  • step-a), step-b) & step-c) the suitable solvent is selected from alcohol solvents, polar solvent, polar-aprotic solvents, ether solvents, ester solvents, hydrocarbon solvents, nitrile solvents, ketone solvents, chloro solvents, acetic acid or their mixtures.
  • a preferred embodiment of the present invention provides a process for the preparation of (3P)-17-iodo-androsta-5,16-dien-3-ol compound of formula-2, comprising of the following steps;
  • step-a) filtering the precipitated solid to provide pure (3P)-17-iodo-androsta-5,16-dien-3-ol compound of formula-2.
  • the suitable solvent is selected from alcohol solvents, polar solvent, polar-aprotic solvents, ether solvents, ester solvents, hydrocarbon solvents, nitrile solvents, ketone solvents, chloro solvents, acetic acid or their mixtures;
  • step-b) the suitable temperature ranges from 35°C to reflux temperature of the solvent used;
  • step-c) the suitable temperature ranges from -20°C to 30°C.
  • a preferred embodiment of the present invention provides a process for the purification of (3P)-17-iodo-androsta-5,16-dien-3-ol compound of formula-2, comprising of; a) Adding methanol to (3P)-17-iodo-androsta-5,16-dien-3-ol compound of formula-2, b) heating the reaction mixture,
  • step-a) of the second and third aspects of the present invention can be obtained from any of the commercial sources or it can be synthesized by any of the known processes.
  • the fourth aspect of the present invention provides a process for the preparation of crystalline form-M of (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula- 1, comprising of;
  • step-c) adding n-heptane to the compound obtained in step-c) and stirring the reaction mixture, e) cooling the reaction mixture to a suitable temperature
  • step-e) filtering the solid to provide crystalline form-M of (3P)-17-(3-pyridinyl)androsta-5,16- dien-3 -yl acetate compound of formula- 1.
  • the suitable temperature ranges between -20°C to 20°C, preferably 0°C to 15°C, more preferably 10-15°C.
  • the fifth aspect of the present invention is to provide crystalline form-S of (3 ⁇ )-17- (3-pyridinyl)androsta-5,16-dien-3-yl acetate hydrochloride salt compound of formula- la, characterized by its powder X-ray diffraction pattern having peaks at 4.5, 7.8, 12.3, 15.0, 15.8, 16.1, 16.7, 17.1, 18.4, 19.7, 20.4, 23.9, 25.1, 26.1 and 28.4 ⁇ 0.2 degrees of 2-theta.
  • the said crystalline form-S is further characterized by its powder X-ray diffraction pattern substantially in accordance with figure-4.
  • the crystalline (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate hydrochloride salt compound of formula- la of the present invention is very useful in the synthesis of highly pure (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1.
  • the sixth aspect of the present invention provides a process for the purification of (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1, comprising of; a) Dissolving the (3 )-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1 in a suitable solvent or mixture of solvents,
  • step-a) filtering the precipitated solid to provide pure (3p)-17-(3-pyridinyl)androsta-5,16-dien-3- yl acetate compound of formula-1.
  • the suitable solvent is selected from alcohol solvents optionally in combination with chloro solvents; and the dissolution of compound of formula- 1 is carried out at 20°C to reflux temperature of the solvent used; preferably at 25-30°C;
  • the suitable anti-solvent is water; and the addition of anti-solvent to the reaction mixture is carried out at 0°C-40°C; preferably at 20-25°C;
  • the ratio of alcohol solvent to the chloro solvent ranges from 20:0.3 volumes, preferably 16:0.4 volumes per one mole ratio of compound of formula- 1.
  • Abiraterone acetate optionally comprises charcoal treatment and it can be carried out at a temperature ranging from 35°C to 80°C; preferably at 35-40°C.
  • a preferred embodiment of the present invention provides a process for the purification of (3 ⁇ )- 17-(3 -pyridinyl)androsta-5, 16-dien-3-yl acetate compound of formula- 1 , comprising of;
  • Another preferred embodiment of the present invention provides a process for the purification of (3p)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula- 1, comprising of;
  • Abiraterone as an impurity in Abiraterone acetate is controlled well within the limits and produces the final API in higher yields and better purity.
  • the (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula- 1 obtained by the process of the present invention is having less than 0.1 %, preferably less than 0.05%, more preferably less than 0.03% of (3p)-17-(3-pyridinyl)-androsta-5,16-dien-3-ol compound of formula-4 as determined by HPLC.
  • a liquid chromatographic system is to be equipped with variable wavelength UV-detector; Column: Symmetry Shield RP18 250x4.6 mm, 5 ⁇ or equivalent; Flow rate: 1.0 mL/minute; Wave length: 252 nm; Injection volume: 5 ⁇ ,; Column temperature: 25°C; Run time: 38 minutes; Mobile phase-A: Weigh accurately 1.36 gm of potassium dihydrogen phosphate in 1000 ml of milli-Q- water, mix well and filter through 0.45 ⁇ nylon membrane filter paper.
  • Mobile phase-B Acetonitrile: water (90:10 v/v); Diluent: Methanol; Elution: Gradient.
  • (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate compound of formula-1 and its hydrochloride salt compound of formula- la of the present invention can be further micronized or milled to get the desired particle size to achieve desired solubility profile based on different forms of pharmaceutical composition requirements.
  • Techniques that may be used for particle size reduction include, but not limited to ball mills, roller and hammer mills and jet mills. Milling or micronization may be performed before drying or after the completion of drying of the product.
  • the present invention is schematically represented as follows:
  • Dehydroepiandrosterone (10 gm) was added to methanol (300 ml) at 25-30°C and stirred the reaction mixture for 10 min at the same temperature.
  • Hydrazine hydrate (5.2 gm), hydrazine sulfate (0.1 gm) and water (0.7 ml) were added to the reaction mixture at 25-30°C. Heated the reaction mixture to 40-45°C and stirred for 6 hrs at the same temperature. After completion of the reaction, cooled the reaction mixture to 20-25°C, water was added and stirred for 90 min at the same temperature. Filtered the solid, washed with n-hexane and dried to get the title compound.
  • 1,1,3,3-tetramethylguanidine (5.7 gm) was added to a pre-cooled mixture of dimethylformamide (10 ml) and iodine (8.35 gm) at 0-5°C.
  • a solution of Dehydroepiandrosterone- 17-hydrazone (5 gm) in dimethylformamide (40 ml) was slowly added to the reaction mixture at 0-5°C and stirred for 90 min at the same temperature.
  • sodium thiosulfate solution (prepared by dissolving 5 gm of sodium thiosulfate in 50 ml of water) to the reaction mixture at 15-20°C and stirred for 90 min at the same temperature. Filtered the solid and washed with water. 15 ml of water was added to the obtained solid at 15-20°C and stirred the reaction mixture for 90 min at the same temperature. Filtered the solid, washed with water and dried to get the title compound.
  • Acetic anhydride (8.75 gm), triethylamine (21.7 gm) followed by 4-dimethylamino pyridine (3.5 gm) were added to a pre-cooled solution of (3P)-17-(3-pyridinyi)-androsta- 5,16-dien-3-ol compound of formula-4 (25 gm) in toluene (250 ml) at 0-10°C and stirred for 2 hrs at the same temperature. After completion of the reaction, water was slowly added to the reaction mixture at 25-30°C and stirred for 10 min at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was extracted with toluene. Separated the organic and aqueous layers and combined the organic layers. Washed the combined organic layers with water and distilled off the solvent completely from the organic layer under reduced pressure to get the title compound.
  • Example-7 Purification of (3P)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate (Formula-l)
  • Example-9 Preparation of crystalline form-M of (3P)-17-(3-pyridinyl)androsta-5,16- dien-3-yl acetate (Formula-1)
  • Acetic anhydride (8.75 gm), triethylamine (21.7 gm) and 4-dimethylaminopyridine (3.5 gm) were added to a pre-cooled solution of (3 )-17-(3-pyridinyl)-androsta-5,16-dien-3- ol compound of formula-4 (25 gm) in toluene (250 ml) at 0-10°C and stirred for 2 hrs at the same temperature. Water was added to the reaction mixture and stirred for 10 min. Both the aqueous and toluene layers were separated and the aqueous layer was extracted with dichloromethane. Combined the organic layers and washed with water. Distilled off the solvent completely from the organic layer under reduced pressure.
  • D(0.1) is 39.26 ⁇
  • D(0.5) is 186.01 ⁇
  • D(0.9) is 411.53 ⁇ ;
  • D(0.1) is 0.88 ⁇
  • D(0.5) is 3.58 ⁇
  • D(0.9) is 8.32 ⁇ .

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  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
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  • Steroid Compounds (AREA)

Abstract

La présente invention concerne un procédé de préparation du composé acétate de (3β)-17-(3-pyridinyl)androsta-5,16-diène-3-yle de formule 1. L'invention concerne également un nouveau polymorphe du composé de formule 1 et son procédé de préparation.
PCT/IN2014/000267 2013-04-26 2014-04-25 PROCÉDÉ DE PRÉPARATION DE L'ACÉTATE DE (3β)-17-(3-PYRIDINYL)ANDROSTA-5,16-DIÈNE-3-YLE ET D'UN POLYMORPHE DE CELUI-CI WO2014188445A1 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016004910A1 (fr) * 2014-07-09 2016-01-14 Zentiva, K.S. Procédé de préparation d'acétate d'abiratérone de haute pureté applicable à l'échelle industrielle
CN111303234A (zh) * 2020-02-28 2020-06-19 江西青峰药业有限公司 一种醋酸阿比特龙单晶及其制备方法
CN112125942A (zh) * 2020-09-28 2020-12-25 湖南新合新生物医药有限公司 醋酸阿比特龙及其中间体的合成方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2282377A (en) * 1993-09-30 1995-04-05 British Tech Group Synthesis of 17-(3-pyridyl) steroids
US5618807A (en) * 1992-03-31 1997-04-08 British Technology Group Limited Method for preparing 17-substituted steroids useful in cancer treatment
CN101768199A (zh) * 2009-12-24 2010-07-07 深圳万乐药业有限公司 醋酸阿比特龙的多晶型物及其制备方法
CN102816200A (zh) * 2012-09-05 2012-12-12 中山大学 一种醋酸阿比特龙的制备方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5618807A (en) * 1992-03-31 1997-04-08 British Technology Group Limited Method for preparing 17-substituted steroids useful in cancer treatment
GB2282377A (en) * 1993-09-30 1995-04-05 British Tech Group Synthesis of 17-(3-pyridyl) steroids
CN101768199A (zh) * 2009-12-24 2010-07-07 深圳万乐药业有限公司 醋酸阿比特龙的多晶型物及其制备方法
CN102816200A (zh) * 2012-09-05 2012-12-12 中山大学 一种醋酸阿比特龙的制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MUKESH ET AL.: "Improved Procedure for Preparation of Abiraterone Acetate", ORGANIC PROCESS RESEARCH AND DEVELOPMENT, vol. 18, no. ISSUE, 2014, pages 555 - 558, XP055210362, DOI: doi:10.1021/op500044p *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016004910A1 (fr) * 2014-07-09 2016-01-14 Zentiva, K.S. Procédé de préparation d'acétate d'abiratérone de haute pureté applicable à l'échelle industrielle
CN111303234A (zh) * 2020-02-28 2020-06-19 江西青峰药业有限公司 一种醋酸阿比特龙单晶及其制备方法
CN112125942A (zh) * 2020-09-28 2020-12-25 湖南新合新生物医药有限公司 醋酸阿比特龙及其中间体的合成方法
CN112125942B (zh) * 2020-09-28 2021-12-14 湖南新合新生物医药有限公司 醋酸阿比特龙及其中间体的合成方法

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