NO341620B1 - Industriell fremgangsmåte for syntese av 17-acetoksy-11-[4-(N,N-dimetylamino)-fenyl]-19-norpregna-4,9-dien-3,20-dion og nye mellomprodukter for prosessen - Google Patents

Industriell fremgangsmåte for syntese av 17-acetoksy-11-[4-(N,N-dimetylamino)-fenyl]-19-norpregna-4,9-dien-3,20-dion og nye mellomprodukter for prosessen

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Publication number
NO341620B1
NO341620B1 NO20090196A NO20090196A NO341620B1 NO 341620 B1 NO341620 B1 NO 341620B1 NO 20090196 A NO20090196 A NO 20090196A NO 20090196 A NO20090196 A NO 20090196A NO 341620 B1 NO341620 B1 NO 341620B1
Authority
NO
Norway
Prior art keywords
norpregna
formula
ethylenedioxy
reacted
diene
Prior art date
Application number
NO20090196A
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English (en)
Other versions
NO20090196L (no
Inventor
Zoltán Tuba
Lajosné DANCSI
György Visky
János Csörgei
Csaba Molnár
Endréné Magyari
Original Assignee
Richter Gedeon Nyrt
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Richter Gedeon Nyrt filed Critical Richter Gedeon Nyrt
Publication of NO20090196L publication Critical patent/NO20090196L/no
Publication of NO341620B1 publication Critical patent/NO341620B1/no

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    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/46—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of glucocorticosteroids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
    • 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
    • C07J41/0077—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • 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

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Foreliggende oppfinnelse angår en ny industriell fremgangsmåte for syntese av solvatfritt 17a-acet-oksy-lip-[4-(N,N-dimetylamino)-fenyl]-19-norpregna-4, 9-dien-3,20-dion [CDB-2914] av formel (I) som er et sterkt antiprogestogent og antiglukokortikoid middel. Oppfinnelsen angår også forbindelser av formel (VII) og (VIII) anvendt som mellomprodukter i prosessen. Fremgangsmåten ifølge oppfinnelsen er følgende: i) 3-(etylendioksy)-østra-5(10),9(11)-dien-17-on av formel (X) omsettes med kalium-acetilyd dannet in situ i tørt tetrahydrofuran på kjent måte, ii) det erholdte 3- (etylendioksy)-17<x-etynyl-17p-hydroksy-østra-5(10),9(11)-dien av formel (IX) omsettes med fenylsulfenylklorid i diklormetan i nærvær av trietyl-amin og eddiksyre, iii) den erholdte isomere blanding av 3-(etylendioksy)-21-(fenylsulfinyl)-19-norpregna- 5 (10), 9(11), 17(20), 20-tetraen av formel (VIII) omsettes først med natriummetoksid i metanol, deretter med trimetylfosfitt, iv) det erholdte 3-(etylendioksy)-17a-hydroksy-2 0-metoksy-19-norpregna-5(10),9(11),20-trien av formel (VII) omsettes med hydrogenklorid
NO20090196A 2006-06-14 2009-01-13 Industriell fremgangsmåte for syntese av 17-acetoksy-11-[4-(N,N-dimetylamino)-fenyl]-19-norpregna-4,9-dien-3,20-dion og nye mellomprodukter for prosessen NO341620B1 (no)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU0600491A HU227112B1 (hu) 2006-06-14 2006-06-14 Ipari eljárás 17-alfa-acetoxi-11-béta-[4-(N,N-dimetil-amino)-fenil]-19-norpregna-4,9-dién-3,20-dion elõállítására és új intermedierek az eljáráshoz
PCT/HU2007/000045 WO2007144674A1 (en) 2006-06-14 2007-05-18 INDUSTRIAL PROCESS FOR THE SYNTHESIS OF 17α-ACETOXY-11β-[4-(N,N-DIMETHYL-AMINO)- PHENYL]-19-NORPREGNA-4,9-DIENE-3,20-DIONE AND NEW INTERMEDIATES OF THE PROCESS

Publications (2)

Publication Number Publication Date
NO20090196L NO20090196L (no) 2009-03-10
NO341620B1 true NO341620B1 (no) 2017-12-11

Family

ID=89986843

Family Applications (1)

Application Number Title Priority Date Filing Date
NO20090196A NO341620B1 (no) 2006-06-14 2009-01-13 Industriell fremgangsmåte for syntese av 17-acetoksy-11-[4-(N,N-dimetylamino)-fenyl]-19-norpregna-4,9-dien-3,20-dion og nye mellomprodukter for prosessen

Country Status (22)

Country Link
US (1) US8110691B2 (no)
EP (1) EP2027140B1 (no)
JP (1) JP5274453B2 (no)
CN (1) CN101466723B (no)
AR (1) AR061052A1 (no)
AU (1) AU2007258955B2 (no)
BR (1) BRPI0713157A2 (no)
CA (1) CA2653552C (no)
DK (1) DK2027140T3 (no)
EA (1) EA015302B1 (no)
ES (1) ES2409841T3 (no)
HU (1) HU227112B1 (no)
IL (1) IL195253A (no)
MX (1) MX2008015972A (no)
NO (1) NO341620B1 (no)
PL (1) PL2027140T3 (no)
PT (1) PT2027140E (no)
RS (1) RS52758B (no)
SI (1) SI2027140T1 (no)
UA (1) UA94269C2 (no)
WO (1) WO2007144674A1 (no)
ZA (1) ZA200809799B (no)

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CN102241722B (zh) * 2010-05-12 2015-11-25 杭州容立医药科技有限公司 一种合成孕酮受体调节剂优力司特的纯化方法
CN102372760A (zh) * 2010-08-12 2012-03-14 杭州容立医药科技有限公司 一种合成孕酮受体调节剂优力司特的合成方法
CN102477060B (zh) * 2010-11-22 2014-08-13 华润紫竹药业有限公司 甾体化合物及其制备方法和用途
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
CN102295674B (zh) * 2011-07-14 2013-04-10 四川大学 获得高纯度17α-乙酰氧基-11β-（4-N,N-二甲氨基苯基）-19-去甲孕甾-4,9-二烯-3,20-二酮的方法
CN102344478B (zh) * 2011-07-22 2013-08-07 上海希迈医药科技有限公司 一种17α-乙酰氧基-11β-(4-N,N-二甲氨基苯基)-19-去甲孕甾-4,9-二烯-3,20-二酮的结晶物及其制备方法
CN102321141B (zh) * 2011-07-22 2013-05-15 上海希迈医药科技有限公司 一种17α-乙酰氧基-11β-（4-N,N-二甲氨基苯基）-19-去甲孕甾-4，9-二烯-3,20-二酮的无定形物及其制备方法
CN103193850A (zh) * 2012-01-04 2013-07-10 北京紫竹药业有限公司 甾体化合物的新晶型及其制备方法
CN104628806A (zh) * 2012-01-19 2015-05-20 华润紫竹药业有限公司 甾体化合物及其制备方法和用途
CN106046099B (zh) * 2012-01-19 2018-03-16 华润紫竹药业有限公司 甾体化合物及其制备方法和用途
CN103755765B (zh) * 2012-04-17 2018-01-02 常州市第四制药厂有限公司 醋酸乌利司他的多晶型及其制备方法
CN102675395B (zh) * 2012-04-17 2014-04-30 常州市第四制药厂有限公司 醋酸乌利司他的多晶型及其制备方法
CN102702296B (zh) * 2012-06-19 2014-09-03 山东诚创医药技术开发有限公司 环-3,20-双(1,2-亚乙基缩醛)-17α-羟基-17β-乙酰基-雌甾-5(10),9(11)-二烯-3-酮的制备方法
US9643994B2 (en) 2012-09-28 2017-05-09 Aska Pharmaceutical Co., Ltd. Crystalline polymorphic form of ulipristal acetate
JP6474722B2 (ja) 2012-09-28 2019-02-27 あすか製薬株式会社 ウリプリスタール酢酸エステルの結晶多形
WO2014050105A1 (en) 2012-09-28 2014-04-03 Aska Pharmaceutical Co., Ltd. Amorphous ulipristal acetate
CN102875629B (zh) * 2012-10-10 2014-11-19 苏州康润医药有限公司 醋酸乌利司他的合成方法
WO2014060888A1 (en) * 2012-10-18 2014-04-24 Lupin Limited Novel process and intermediate for preparation of ulipristal
CN102942612A (zh) * 2012-10-30 2013-02-27 四川大学 一种合成醋酸乌利司他的新方法
CN103804456B (zh) * 2012-11-15 2017-08-04 上海创诺医药集团有限公司 醋酸乌利司他中间体及其制备方法
CN103145787B (zh) * 2012-12-25 2017-02-22 常州市亚邦医药研究所有限公司 制备醋酸优力司特关键中间体的新方法
CN103087140A (zh) * 2013-03-04 2013-05-08 四川尚锐生物医药有限公司 一种醋酸优力司特多晶型的制备方法
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
CN103755763A (zh) * 2013-12-30 2014-04-30 烟台东诚生化股份有限公司 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-3,20-二酮的制备方法
CN104530169B (zh) * 2014-12-12 2017-09-12 成都化润药业有限公司 一种醋酸乌利司他及其中间体的制备方法
CN106986911B (zh) * 2017-03-23 2019-05-10 湖南玉新药业有限公司 地塞米松关键中间体联烯亚砜物的制备方法
CN106986908B (zh) * 2017-03-23 2019-05-10 湖南玉新药业有限公司 倍他米松的制备方法
CN108558982A (zh) * 2018-05-21 2018-09-21 郑州泰丰制药有限公司 一种新型醋酸乌利司他以及其生产制造方法
CN109053846B (zh) * 2018-08-14 2020-01-07 台州仙琚药业有限公司 制备醋酸优力司特双缩酮的方法
CN111349137A (zh) * 2018-12-21 2020-06-30 北京启慧生物医药有限公司 一种绿色合成醋酸乌利司他中间体及醋酸乌利司他的方法
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

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Also Published As

Publication number Publication date
CN101466723B (zh) 2011-11-02
CN101466723A (zh) 2009-06-24
AU2007258955A1 (en) 2007-12-21
HU0600491D0 (en) 2006-08-28
JP5274453B2 (ja) 2013-08-28
EP2027140A1 (en) 2009-02-25
DK2027140T3 (da) 2013-06-03
JP2009539964A (ja) 2009-11-19
PT2027140E (pt) 2013-06-04
UA94269C2 (en) 2011-04-26
NO20090196L (no) 2009-03-10
RS52758B (en) 2013-08-30
CA2653552A1 (en) 2007-12-21
EP2027140B1 (en) 2013-03-13
IL195253A (en) 2011-11-30
PL2027140T3 (pl) 2013-09-30
IL195253A0 (en) 2009-08-03
US8110691B2 (en) 2012-02-07
AR061052A1 (es) 2008-07-30
EA015302B1 (ru) 2011-06-30
CA2653552C (en) 2013-04-23
AU2007258955B2 (en) 2012-09-20
HUP0600491A2 (en) 2008-02-28
WO2007144674A1 (en) 2007-12-21
EA200900015A1 (ru) 2009-04-28
ZA200809799B (en) 2009-11-25
US20090187032A1 (en) 2009-07-23
HU227112B1 (hu) 2010-07-28
MX2008015972A (es) 2009-01-12
ES2409841T3 (es) 2013-06-28
BRPI0713157A2 (pt) 2012-04-03
SI2027140T1 (sl) 2013-07-31

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