CN102516345B - 醋酸乌利司他及其关键中间体的制备方法 - Google Patents

醋酸乌利司他及其关键中间体的制备方法 Download PDF

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Publication number
CN102516345B
CN102516345B CN201110339479.8A CN201110339479A CN102516345B CN 102516345 B CN102516345 B CN 102516345B CN 201110339479 A CN201110339479 A CN 201110339479A CN 102516345 B CN102516345 B CN 102516345B
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compound
formula
reaction
reagent
preparation
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Expired - Fee Related
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CN201110339479.8A
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English (en)
Chinese (zh)
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CN102516345A (zh
Inventor
罗军芝
孙永强
罗讯
严益民
王兆军
钱明霞
屠永锐
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Changzhou City No4 Pharmaceutical Factory Co Ltd
SHANGHAI UTOPHARM CO Ltd
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Changzhou City No4 Pharmaceutical Factory Co Ltd
SHANGHAI UTOPHARM CO Ltd
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Application filed by Changzhou City No4 Pharmaceutical Factory Co Ltd, SHANGHAI UTOPHARM CO Ltd filed Critical Changzhou City No4 Pharmaceutical Factory Co Ltd
Priority to CN201110339479.8A priority Critical patent/CN102516345B/zh
Publication of CN102516345A publication Critical patent/CN102516345A/zh
Priority to AU2012331996A priority patent/AU2012331996B2/en
Priority to RU2014120908A priority patent/RU2624007C2/ru
Priority to ES12845071.5T priority patent/ES2669052T3/es
Priority to EP12845071.5A priority patent/EP2774933B1/en
Priority to BR112014010263-5A priority patent/BR112014010263B1/pt
Priority to PL12845071T priority patent/PL2774933T3/pl
Priority to MX2014005245A priority patent/MX343774B/es
Priority to CA2851399A priority patent/CA2851399C/en
Priority to US14/233,757 priority patent/US9163058B2/en
Priority to PCT/CN2012/000952 priority patent/WO2013063859A1/zh
Priority to HUE12845071A priority patent/HUE037674T2/hu
Priority to JP2014534915A priority patent/JP5913599B2/ja
Priority to IN2562CHN2014 priority patent/IN2014CN02562A/en
Application granted granted Critical
Publication of CN102516345B publication Critical patent/CN102516345B/zh
Expired - Fee Related legal-status Critical Current
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0077—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 substituted in position 11-beta by a carbon atom, further substituted by a group comprising at least one further carbon atom
    • C07J41/0083—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 substituted in position 11-beta by a carbon atom, further substituted by a group comprising at least one further carbon atom substituted in position 11-beta by an optionally substituted phenyl group not further condensed with other rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/18—Feminine contraceptives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J21/005—Ketals
    • C07J21/006—Ketals at position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0094—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing nitrile radicals, including thiocyanide radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
    • C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
    • C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
    • C07J7/004—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa
    • C07J7/0045—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa not substituted in position 16
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • C07J71/0005—Oxygen-containing hetero ring
    • C07J71/001—Oxiranes
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Toxicology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Steroid Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
CN201110339479.8A 2011-01-11 2011-11-01 醋酸乌利司他及其关键中间体的制备方法 Expired - Fee Related CN102516345B (zh)

Priority Applications (14)

Application Number Priority Date Filing Date Title
CN201110339479.8A CN102516345B (zh) 2011-11-01 2011-11-01 醋酸乌利司他及其关键中间体的制备方法
CA2851399A CA2851399C (en) 2011-11-01 2012-07-12 Ulipristal acetate preparation method and intermediate thereof
PCT/CN2012/000952 WO2013063859A1 (zh) 2011-11-01 2012-07-12 醋酸乌利司他的制备方法及其中间体
ES12845071.5T ES2669052T3 (es) 2011-11-01 2012-07-12 Método de preparación de acetato de ulipristal y sus intermedios
EP12845071.5A EP2774933B1 (en) 2011-11-01 2012-07-12 Ulipristal acetate preparation method and intermediate thereof
BR112014010263-5A BR112014010263B1 (pt) 2011-11-01 2012-07-12 Método de preparação do acetato de ulipristal e intermediário deste
PL12845071T PL2774933T3 (pl) 2011-11-01 2012-07-12 Sposób wytwarzania octanu uliprystalu i jego związku pośredniego
MX2014005245A MX343774B (es) 2011-11-01 2012-07-12 Metodo de preparacion de acetato de ulipristal y su intermediario.
AU2012331996A AU2012331996B2 (en) 2011-11-01 2012-07-12 Ulipristal acetate preparation method and intermediate thereof
US14/233,757 US9163058B2 (en) 2011-01-11 2012-07-12 Method for preparing ulipristal acetate and key intermediate thereof
RU2014120908A RU2624007C2 (ru) 2011-11-01 2012-07-12 Способ получения улипристала ацетата и его промежуточных продуктов
HUE12845071A HUE037674T2 (hu) 2011-11-01 2012-07-12 Eljárás uliprisztál-acetát és intermedierjének elõállítására
JP2014534915A JP5913599B2 (ja) 2011-11-01 2012-07-12 酢酸ウリプリスタルの製作方法及び中間体
IN2562CHN2014 IN2014CN02562A (https=) 2011-11-01 2012-07-12

Applications Claiming Priority (1)

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CN201110339479.8A CN102516345B (zh) 2011-11-01 2011-11-01 醋酸乌利司他及其关键中间体的制备方法

Publications (2)

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CN102516345A CN102516345A (zh) 2012-06-27
CN102516345B true CN102516345B (zh) 2014-11-26

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Country Link
US (1) US9163058B2 (https=)
EP (1) EP2774933B1 (https=)
JP (1) JP5913599B2 (https=)
CN (1) CN102516345B (https=)
AU (1) AU2012331996B2 (https=)
BR (1) BR112014010263B1 (https=)
CA (1) CA2851399C (https=)
ES (1) ES2669052T3 (https=)
HU (1) HUE037674T2 (https=)
IN (1) IN2014CN02562A (https=)
MX (1) MX343774B (https=)
PL (1) PL2774933T3 (https=)
RU (1) RU2624007C2 (https=)
WO (1) WO2013063859A1 (https=)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102516345B (zh) * 2011-11-01 2014-11-26 上海优拓医药科技有限公司 醋酸乌利司他及其关键中间体的制备方法
CN103073612B (zh) * 2013-02-04 2015-11-04 山东大学 醋酸乌利司他关键中间体的制备方法
CN103145788B (zh) * 2013-03-25 2015-08-19 浙江仙琚制药股份有限公司 醋酸优力司特关键中间体的制备方法
HU230319B1 (hu) 2013-10-01 2016-01-28 Richter Gedeon Nyrt. Ipari eljárás szteroid hatóanyagok előállítására
CN104558089A (zh) * 2013-10-25 2015-04-29 上海医药工业研究院 一种3-(亚乙二氧基)-17β-氰基-17α-羟基-雌-5(10)，9(11)-二烯的制备方法
CN103641881A (zh) * 2013-11-22 2014-03-19 湖南新合新生物医药有限公司 乌利司他中间体的制备方法
CN103601785A (zh) * 2013-11-25 2014-02-26 四川大学 一种醋酸优力斯特新的合成方法
CN104774231A (zh) * 2014-01-13 2015-07-15 上海医药工业研究院 17α-羟基-19-去甲孕甾-4,9-二烯-3,20-二酮的制备工艺
CN105294808B (zh) * 2015-09-28 2017-08-25 国家卫生计生委科学技术研究所 醋酸乌利司他晶g型物质及制备方法和其组合物与用途
CN105237607B (zh) * 2015-10-29 2018-10-02 国家卫生计生委科学技术研究所 醋酸乌利司他晶k型物质及制备方法和其组合物与用途
CN105566431B (zh) * 2016-02-19 2017-11-24 常州市第四制药厂有限公司 一种醋酸乌利司他的杂质及其制备和检测方法
CN105566432B (zh) * 2016-02-19 2017-11-03 常州四药制药有限公司 一种醋酸乌利司他的杂质及其制备和检测方法
CN105669810B (zh) * 2016-02-19 2017-05-10 常州市第四制药厂有限公司 一种醋酸乌利司他的杂质及其制备和检测方法
CN105669819B (zh) * 2016-03-23 2017-06-23 浙江仙琚制药股份有限公司 制备醋酸优力司特双缩酮异构体的方法
CN106866778A (zh) * 2017-04-25 2017-06-20 广西万德药业有限公司 一种5(10)位α环氧甾族化合物的合成方法
CN108070016B (zh) * 2017-12-29 2020-07-07 广西万德药业有限公司 甾体环氧异构体的循环利用方法
CN108558981B (zh) * 2018-05-08 2020-05-08 浙江仙琚制药股份有限公司 制备双缩酮的方法
JP7303618B2 (ja) * 2018-10-05 2023-07-05 日本精化株式会社 スフィンゴリン脂質前駆体及びその製造方法、並びに、スフィンゴリン脂質の製造方法
CN110256519B (zh) * 2019-05-23 2021-06-08 江苏联环药业股份有限公司 一锅法制备醋酸乌利司他的方法
CN111018935A (zh) * 2019-12-31 2020-04-17 浙江仙居君业药业有限公司 一种醋酸乌利斯他中间体的合成方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4954490A (en) * 1988-06-23 1990-09-04 Research Triangle Institute 11 β-substituted progesterone analogs
US5929262A (en) * 1995-03-30 1999-07-27 The United States Of America As Represented By The Department Of Health And Human Services Method for preparing 17α-acetoxy-11β-(4-N, N-dimethylaminophyl)-19-Norpregna-4,9-diene-3, 20-dione, intermediates useful in the method, and methods for the preparation of such intermediates
WO2004078709A2 (en) * 2003-02-28 2004-09-16 The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services METHOD FOR PREPARING 17 α-ACETOXY-11β-(4-N,N-DIMETHYLAMINOPHENYL)-19-NORPREGNA-4,9-DIENE-3,20-DIONE, INTERMEDIATES THEREOF, AND METHODS FOR THE PREPARATION OF SUCH INTERMEDIATES
CN101048394A (zh) * 2004-06-29 2007-10-03 查塔姆生物技术有限公司 太平洋紫杉醇向多烯紫杉醇的半合成转化
CN101466723A (zh) * 2006-06-14 2009-06-24 吉瑞工厂 用于合成17α-乙酰氧基-11β-[4-(N,N-二甲基-氨基)-苯基]-19-去甲孕甾-4,9-二烯-3,20-二酮的工业生产方法和用于所述方法的新的中间体
CN101622268A (zh) * 2007-06-27 2010-01-06 吉瑞工厂 合成17-乙酰氧基-11β-[4-(二甲氨基)-苯基]-21-甲氧基-19-去甲孕-4,9-二烯-3,20-二酮的工业方法和该方法的关键中间体

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5352809A (en) * 1986-10-10 1994-10-04 Gist-Brocades N.V. 9-alpha-hydroxy steroids, process for their preparation, process for the preparation of the corresponding 9(11)-dehydro derivatives and pharmaceutical preparations containing such steroids
US6020328A (en) * 1998-03-06 2000-02-01 Research Triangle Institute 20-keto-11β-arylsteroids and their derivatives having agonist or antagonist hormonal properties
DK1265911T3 (da) * 2000-03-17 2008-09-29 Us Gov Health & Human Serv 17-alfa-substitueret-11-beta-substitueret-4-aryl og 21-substitueret 19-norpregnadiendion som antiprogestationelle midler
CN102516345B (zh) * 2011-11-01 2014-11-26 上海优拓医药科技有限公司 醋酸乌利司他及其关键中间体的制备方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4954490A (en) * 1988-06-23 1990-09-04 Research Triangle Institute 11 β-substituted progesterone analogs
US5929262A (en) * 1995-03-30 1999-07-27 The United States Of America As Represented By The Department Of Health And Human Services Method for preparing 17α-acetoxy-11β-(4-N, N-dimethylaminophyl)-19-Norpregna-4,9-diene-3, 20-dione, intermediates useful in the method, and methods for the preparation of such intermediates
WO2004078709A2 (en) * 2003-02-28 2004-09-16 The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services METHOD FOR PREPARING 17 α-ACETOXY-11β-(4-N,N-DIMETHYLAMINOPHENYL)-19-NORPREGNA-4,9-DIENE-3,20-DIONE, INTERMEDIATES THEREOF, AND METHODS FOR THE PREPARATION OF SUCH INTERMEDIATES
CN101048394A (zh) * 2004-06-29 2007-10-03 查塔姆生物技术有限公司 太平洋紫杉醇向多烯紫杉醇的半合成转化
CN101466723A (zh) * 2006-06-14 2009-06-24 吉瑞工厂 用于合成17α-乙酰氧基-11β-[4-(N,N-二甲基-氨基)-苯基]-19-去甲孕甾-4,9-二烯-3,20-二酮的工业生产方法和用于所述方法的新的中间体
CN101622268A (zh) * 2007-06-27 2010-01-06 吉瑞工厂 合成17-乙酰氧基-11β-[4-(二甲氨基)-苯基]-21-甲氧基-19-去甲孕-4,9-二烯-3,20-二酮的工业方法和该方法的关键中间体

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
刘宏斌 等.醋酸乌利司他合成路线图解.《中国医药工业杂志》.2011,第42卷(第01期),第73-75页. *
醋酸乌利司他合成路线图解;刘宏斌 等;《中国医药工业杂志》;20110110;第42卷(第01期);第73-73页 *

Also Published As

Publication number Publication date
BR112014010263A2 (pt) 2017-04-18
BR112014010263B1 (pt) 2021-11-03
ES2669052T3 (es) 2018-05-23
JP2014528459A (ja) 2014-10-27
EP2774933A1 (en) 2014-09-10
US20140296510A1 (en) 2014-10-02
JP5913599B2 (ja) 2016-04-27
RU2014120908A (ru) 2015-12-10
US9163058B2 (en) 2015-10-20
CA2851399C (en) 2019-06-25
AU2012331996B2 (en) 2015-04-23
CA2851399A1 (en) 2013-05-10
EP2774933A4 (en) 2015-07-08
PL2774933T3 (pl) 2018-08-31
RU2624007C2 (ru) 2017-06-30
WO2013063859A1 (zh) 2013-05-10
HUE037674T2 (hu) 2018-09-28
EP2774933B1 (en) 2018-02-21
IN2014CN02562A (https=) 2015-08-07
MX2014005245A (es) 2014-08-22
AU2012331996A1 (en) 2014-05-15
CN102516345A (zh) 2012-06-27
MX343774B (es) 2016-11-23

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