AR061052A1 - Proceso industrial para la sintesis de 17(alfa)-acetoxi-11(beta)-[-4-n,n-dimetil-amino)- fenil]-19-norpregna-4,9-dieno- 3,20-diona y productos intermedios del proceso - Google Patents

Proceso industrial para la sintesis de 17(alfa)-acetoxi-11(beta)-[-4-n,n-dimetil-amino)- fenil]-19-norpregna-4,9-dieno- 3,20-diona y productos intermedios del proceso

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Publication number
AR061052A1
AR061052A1 ARP070102187A ARP070102187A AR061052A1 AR 061052 A1 AR061052 A1 AR 061052A1 AR P070102187 A ARP070102187 A AR P070102187A AR P070102187 A ARP070102187 A AR P070102187A AR 061052 A1 AR061052 A1 AR 061052A1
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AR
Argentina
Prior art keywords
formula
norpregna
17alpha
ethylene
dioxy
Prior art date
Application number
ARP070102187A
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English (en)
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.)
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Publication date
Application filed by Richter Gedeon Nyrt filed Critical Richter Gedeon Nyrt
Publication of AR061052A1 publication Critical patent/AR061052A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J21/00Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J21/005Ketals
    • C07J21/006Ketals at position 3
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J21/00Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/24Drugs for disorders of the endocrine system of the sex hormones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/38Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/46Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of glucocorticosteroids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J31/00Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J31/00Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • C07J31/006Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J41/00Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J41/00Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0077Normal 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
    • C07J41/0083Normal 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J71/00Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J71/00Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • C07J71/0005Oxygen-containing hetero ring
    • C07J71/001Oxiranes

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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

Reivindicacion 1: Un proceso industrial para la síntesis de 17alfa-acetoxi-11beta-[-4-N,N-dimetil-amino)-fenil]-19-norpregna-4,9-dieno-3,20-diona libre de solvato de la formula (1) vía formacion de cetal a partir de 3-(etileno-dioxi)-17alfa--hidroxi- 19-norpregna-5(10),9(11)-dieno-20-ona de la formula (6), formacion de epoxidos en posicion 5,10 del 3,3,20,20-bis(etiIeno-dioxi)-17alfa-hidroxi-19-norpregna-5(10),9 (11)-dieno de la formula (5), reaccion del 3,3,20,20-bis8etileno-dioxi)-17alfa- hidroxi-5,10-epoxi-9-norpregna-9(11)-eno de la formula (4) con el reactivo de Grignard obtenido de bromo-N,N-dimetil-anilina, desproteccion del así formado 3,3,20,20-bis(etileno-dioxi)-5alfa,17alfa-dihidroxi-11beta-[4-(N,N-dimetilamino)-fenil]-19- norpregna-9(11)-eno de la formula (3), acetilacion del 11beta-[4-(N,N- dimetilamino)-fenil]-17alfa-hidroxi-19-norpregna-4,9-dieno-3,20-diona obtenido de la formula (2) y la liberacion final del producto deseado, caracterizado porque, (i) 3-(etileno- dioxi)-estra-5(10),9(11)-dieno-17-ona de la formula (10) se hace reaccionar con acetilida potásica in situ en tetrahidrofurano seco por un método conocido; ii) 3-(etileno-dioxi)-17alfa-etinil-17beta-hidroxi-estra-5(10),9(11 )-dieno de la formula (9) obtenido se hace reaccionar con cloruro de fenilsulfenilo en diclorometano en la presencia de trietilamina y ácido acético; iii) la mezcla isomérica obtenida de 3-(etileno-dioxi)-21(fenil-sulfinil)-19-norpregna-5(10),9(11),17(20),20-tetraeno de la formula (8) se hace reaccionar primero con metoxido de sodio en metanol, luego con fosfito de trimetilo, iv) 3-(etileno-dioxi)-17alfa-hidroxi-20-metoxi-19-norpregna-5(1 0),(11),20-trieno obtenido la formula (7) se hace reaccionar con cloruro de hidrogeno en metanol, luego v) 3-(etileno-.dioxi)-17alfa-hidroxi-19-norpregna-5(10),9(11)-dieno-20-ona de la formula (6) obtenido se hace reaccionar con etilenglicol en diclorometano en la presencia de ortoformato de trimetilo y ácido p- toluenosulfonico por un método conocido; vi) 3,3,20,20-bis(etileno-dioxi)-17alfa-hidroxi-19-norpregna-5(10),9(11)-dieno de la formula (5) obtenido se hizo reaccionar con peroxido de hidrogeno en una mezcla de piridina y diclorometano en la presencia de hexacloroacetona por un método conocido; vii) 3,3,20,20-bis(etileno-dioxi)-17alfa-hidroxi-5,10-epoxi-19-norpregna-9(11)-eno de la formula (4) obtenido que contiene aproximadamente una mezcla 1:1 de 5alfa, 10alfa- y 5beta,10beta-epoxidos con un reactivo de Grignard obtenido a partir de 4-bromo-N,N-dimetil-anilina en tetrahidrofurano en la presencia de catalizador cloruro de cobre (1) sin la separacion de isomeros por un método conocido; viii) 3,3,20,20-bis(etileno-dioxi)-5alfa,17alfa- dihidroxi-11b-[4-(N,N-dimetilamino)-fenil]-9-norpregna-9(11)-eno obtenido de la formula (3) se reacciona con sulfato de hidrogeno potásico en agua por un método conocido; ix) acetilacion de 11beta-[4-(N,N-dimetilamino)-fenil]-17alfa-hidroxi-19- norpregna-4,9-dieno-3,10-diona de la formula (2) obtenido con anhídrido acético en la presencia de ácido perclorico por un método conocido, y, finalmente, x) liberacion del compuesto libre de solvato de la formula (1) a partir del solvato obtenido que contiene el compuesto de la formula (1) en una mezcla 1:1 de etanol y agua a 70°C.
ARP070102187A 2006-06-14 2007-05-21 Proceso industrial para la sintesis de 17(alfa)-acetoxi-11(beta)-[-4-n,n-dimetil-amino)- fenil]-19-norpregna-4,9-dieno- 3,20-diona y productos intermedios del proceso AR061052A1 (es)

Applications Claiming Priority (1)

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

Publications (1)

Publication Number Publication Date
AR061052A1 true AR061052A1 (es) 2008-07-30

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ID=89986843

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Country Status (22)

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

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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
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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
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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
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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
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NO341620B1 (no) 2017-12-11
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
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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