RU2004100309A - Способ получения флуметазона, соединение - Google Patents
Способ получения флуметазона, соединение Download PDFInfo
- Publication number
- RU2004100309A RU2004100309A RU2004100309/04A RU2004100309A RU2004100309A RU 2004100309 A RU2004100309 A RU 2004100309A RU 2004100309/04 A RU2004100309/04 A RU 2004100309/04A RU 2004100309 A RU2004100309 A RU 2004100309A RU 2004100309 A RU2004100309 A RU 2004100309A
- Authority
- RU
- Russia
- Prior art keywords
- flumethasone
- compound
- acetate
- formula
- reaction
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0061—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16
- C07J5/0069—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group
- C07J5/0076—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group by an alkyl group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J3/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom
- C07J3/005—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom the carbon atom being part of a carboxylic function
-
- 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
- C07J71/0015—Oxiranes at position 9(11)
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Rheumatology (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Reduction Or Emphasis Of Bandwidth Of Signals (AREA)
- Oscillators With Electromechanical Resonators (AREA)
- Control Of Combustion (AREA)
- Anti-Oxidant Or Stabilizer Compositions (AREA)
Claims (8)
1. Способ получения флуметазона (6α,9α-дифтор-11β,17α,21-тригидрокси-16α-метилпрегна-1,4-диен-3,20-диона), флуметазон 21-ацетата или его 17-карбоксиландростенового аналога формулы:
включающий
(а) реакцию соединения формулы (II)
с хлористым бензоилом с образованием 3-енольного сложного эфира формулы (IIIa):
b) реакцию енолбензоата (IIIa) с электрофильным фторирующим агентом для введения фтора в С6-положение с образованием соединения формулы (IIIb):
(с) снятие защитной группы с положения С3 соединения (IIIb) с образованием соединения формулы (IV):
(d) фторирование 9,11-эпоксигруппы соединения IV реакцией с фтористоводородной кислотой с получением 21-ацетата флуметазона, и необязательно
(е) гидролиз 21-ацетата флуметазона в присутствии или в отсутствие окисляющего агента с получением соединения (I) или флуметазона, соответственно.
2. Способ по п.1, в котором 21-ацетат флуметазона на стадии (е) подвергают гидролизу раствором гидроксида калия в метаноле.
3. Способ по п.1 или 2, в котором окисляющий агент, используемый на стадии (е), представляет собой водный раствор пероксида водорода.
4. Способ по п.1, в котором электрофильный фторирующий агент представляет собой 1-(хлорметил)-4-фтор-1,4-диазонийбицикло[2.2.2]октан-бис(тетрафторборат).
5. Способ по п.1, в котором снятие защитной группы в положении С3 на стадии (с) осуществляют с использованием водного раствора метабисульфита и аммиака.
6. Способ по п.1, в котором реакционная среда, используемая на стадии (а), представляет собой N,N’-диметилацетамид и пиридин, а реакционная среда, используемая на стадии (b), представляет собой ацетонитрил в присутствии воды.
7. Способ по п.1, в котором температура реакции на стадии (а) составляет от 80 до 85°С, а на стадии (b) - -5°C±2°C.
8. Соединение формулы (V):
в котором Х представляет собой водород или фтор.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PT102.628 | 2001-06-12 | ||
| PT102628A PT102628B (pt) | 2001-06-12 | 2001-06-12 | Novo processo de preparação de flumetasona e do seu análogo 17-carboxilo androsteno |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2004100309A true RU2004100309A (ru) | 2005-07-10 |
| RU2260596C1 RU2260596C1 (ru) | 2005-09-20 |
Family
ID=20086054
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2004100309/04A RU2260596C1 (ru) | 2001-06-12 | 2002-06-11 | Способ получения флуметазона, соединение |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US6528666B1 (ru) |
| EP (1) | EP1395603B1 (ru) |
| JP (1) | JP4095018B2 (ru) |
| CN (1) | CN1244593C (ru) |
| AT (1) | ATE460422T1 (ru) |
| AU (1) | AU2002310616B2 (ru) |
| CA (1) | CA2450661C (ru) |
| CY (1) | CY1109960T1 (ru) |
| DE (1) | DE60235625D1 (ru) |
| DK (1) | DK1395603T3 (ru) |
| ES (1) | ES2338768T3 (ru) |
| IL (2) | IL159343A0 (ru) |
| NO (1) | NO326153B1 (ru) |
| NZ (1) | NZ530536A (ru) |
| PL (1) | PL206731B1 (ru) |
| PT (1) | PT102628B (ru) |
| RU (1) | RU2260596C1 (ru) |
| WO (1) | WO2002100878A1 (ru) |
| ZA (1) | ZA200309656B (ru) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003047329A2 (en) * | 2001-11-29 | 2003-06-12 | Taro Pharmaceuticals U.S.A., Inc. | Method for the preparation of 6-alpha-fluoro corticosteroids |
| CA2509366C (en) * | 2002-12-09 | 2008-04-15 | Sicor Inc. | Process for the preparation of pregnanes |
| EP1526139A1 (en) * | 2003-10-24 | 2005-04-27 | S.N.I.F.F. Italia S.P.A. | A process for preparing highly pure androstane 17-beta-carboxylic acids and androstane 17-beta-carbothioic acid fluoromethyl esters |
| CN100429221C (zh) * | 2005-10-31 | 2008-10-29 | 浙江仙琚制药股份有限公司 | 皮质激素的合成方法 |
| CN101759761B (zh) * | 2008-11-28 | 2012-08-08 | 天津金耀集团有限公司 | 含有6α-F的甾体化合物的制备方法 |
| US20120178124A1 (en) | 2009-01-07 | 2012-07-12 | Mitsubishi Chemical Corporation | Sterol side chain-cleaving enzyme protein and use thereof |
| CN101942002A (zh) * | 2010-09-24 | 2011-01-12 | 岳阳环宇药业有限公司 | 一种甾体21位酯化物的精制工艺 |
| ITMI20122200A1 (it) * | 2012-12-20 | 2014-06-21 | Trifarma Spa | Processo per la preparazione di 6-alfa-fluoro pregnani |
| RU2532902C1 (ru) * | 2013-07-12 | 2014-11-20 | Российская Федерация, от имени которой выступает Министерство промышленности и торговли Российской Федерации (Минпромторг России) | Способ получения 11бета, 17альфа, 21-тригидрокси-16альфа-метил-9альфа-фторпрегна-1,4-диен-3,20-диона (дексаметазона) из фитостерина |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3499016A (en) | 1958-08-04 | 1970-03-03 | Upjohn Co | 6alpha-fluoro-16alpha-methyl derivatives of the pregnane series |
| US3636010A (en) | 1968-12-23 | 1972-01-18 | Ciba Geigy Corp | Esters of steroid-17-carboxylic acids |
| NL187577C (nl) * | 1978-04-05 | 1991-11-18 | Sibla Srl | 3-acetoxy-9beta,11beta-epoxy-pregna-1,3,5-trienen, werkwijze voor de bereiding daarvan en werkwijze voor de bereiding van 6alfa-halogeen-pregna-1,4-dieen-3-onen. |
| US4188322A (en) * | 1978-04-28 | 1980-02-12 | Blasinachim S.P.A. | Process for the preparation of 6-halo-pregnanes |
| FR2701262B1 (fr) | 1993-02-05 | 1995-03-24 | Roussel Uclaf | Nouveau procédé de préparation de stéroïdes 6 alpa, 9 alpha-difluorés et nouveaus intermédiaires. |
| IT1319663B1 (it) * | 2000-11-17 | 2003-10-23 | Farmabios Srl | Processo per la preparazione di fluoro-steroidi. |
-
2001
- 2001-06-12 PT PT102628A patent/PT102628B/pt active IP Right Grant
-
2002
- 2002-06-06 US US10/162,862 patent/US6528666B1/en not_active Expired - Lifetime
- 2002-06-11 EP EP02735607A patent/EP1395603B1/en not_active Expired - Lifetime
- 2002-06-11 DE DE60235625T patent/DE60235625D1/de not_active Expired - Lifetime
- 2002-06-11 RU RU2004100309/04A patent/RU2260596C1/ru not_active IP Right Cessation
- 2002-06-11 AT AT02735607T patent/ATE460422T1/de active
- 2002-06-11 CA CA002450661A patent/CA2450661C/en not_active Expired - Fee Related
- 2002-06-11 CN CNB028117662A patent/CN1244593C/zh not_active Expired - Fee Related
- 2002-06-11 DK DK02735607.0T patent/DK1395603T3/da active
- 2002-06-11 WO PCT/GB2002/002644 patent/WO2002100878A1/en active IP Right Grant
- 2002-06-11 ES ES02735607T patent/ES2338768T3/es not_active Expired - Lifetime
- 2002-06-11 IL IL15934302A patent/IL159343A0/xx unknown
- 2002-06-11 AU AU2002310616A patent/AU2002310616B2/en not_active Ceased
- 2002-06-11 JP JP2003503644A patent/JP4095018B2/ja not_active Expired - Fee Related
- 2002-06-11 PL PL367843A patent/PL206731B1/pl unknown
- 2002-06-11 NZ NZ530536A patent/NZ530536A/en not_active IP Right Cessation
-
2003
- 2003-12-11 IL IL159343A patent/IL159343A/en not_active IP Right Cessation
- 2003-12-11 NO NO20035517A patent/NO326153B1/no not_active IP Right Cessation
- 2003-12-12 ZA ZA200309656A patent/ZA200309656B/xx unknown
-
2010
- 2010-04-07 CY CY20101100318T patent/CY1109960T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO20035517D0 (no) | 2003-12-11 |
| IL159343A0 (en) | 2004-06-01 |
| PL206731B1 (pl) | 2010-09-30 |
| NO326153B1 (no) | 2008-10-06 |
| US6528666B1 (en) | 2003-03-04 |
| WO2002100878A1 (en) | 2002-12-19 |
| AU2002310616A2 (en) | 2002-12-23 |
| DE60235625D1 (de) | 2010-04-22 |
| ATE460422T1 (de) | 2010-03-15 |
| CA2450661A1 (en) | 2002-12-19 |
| PT102628B (pt) | 2010-09-09 |
| JP4095018B2 (ja) | 2008-06-04 |
| RU2260596C1 (ru) | 2005-09-20 |
| CA2450661C (en) | 2008-01-08 |
| PT102628A (pt) | 2002-12-31 |
| PL367843A1 (en) | 2005-03-07 |
| CN1531544A (zh) | 2004-09-22 |
| JP2004534795A (ja) | 2004-11-18 |
| EP1395603B1 (en) | 2010-03-10 |
| ZA200309656B (en) | 2004-06-22 |
| AU2002310616B2 (en) | 2007-08-30 |
| CY1109960T1 (el) | 2014-09-10 |
| DK1395603T3 (da) | 2010-05-10 |
| IL159343A (en) | 2010-11-30 |
| CN1244593C (zh) | 2006-03-08 |
| NZ530536A (en) | 2005-05-27 |
| ES2338768T3 (es) | 2010-05-12 |
| EP1395603A1 (en) | 2004-03-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20200612 |