BRPI0412186A - processo para a sìntese de d-(17alfa)-13-etil-17-hidroxi-18,19-dinorpregn-4-eno-20-i no-3-ona-oxima de pureza elevada - Google Patents
processo para a sìntese de d-(17alfa)-13-etil-17-hidroxi-18,19-dinorpregn-4-eno-20-i no-3-ona-oxima de pureza elevadaInfo
- Publication number
- BRPI0412186A BRPI0412186A BRPI0412186-4A BRPI0412186A BRPI0412186A BR PI0412186 A BRPI0412186 A BR PI0412186A BR PI0412186 A BRPI0412186 A BR PI0412186A BR PI0412186 A BRPI0412186 A BR PI0412186A
- Authority
- BR
- Brazil
- Prior art keywords
- dinorpregn
- ethyl
- water
- acetoxy
- yne
- Prior art date
Links
- 238000000034 method Methods 0.000 title abstract 4
- 230000015572 biosynthetic process Effects 0.000 title abstract 3
- 238000003786 synthesis reaction Methods 0.000 title abstract 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 abstract 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract 3
- 238000006243 chemical reaction Methods 0.000 abstract 3
- 239000000047 product Substances 0.000 abstract 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 2
- 239000003610 charcoal Substances 0.000 abstract 2
- 238000001914 filtration Methods 0.000 abstract 2
- 229960004400 levonorgestrel Drugs 0.000 abstract 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 abstract 2
- 238000003756 stirring Methods 0.000 abstract 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 abstract 2
- ISHXLNHNDMZNMC-VTKCIJPMSA-N (3e,8r,9s,10r,13s,14s,17r)-13-ethyl-17-ethynyl-3-hydroxyimino-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-ol Chemical compound O/N=C/1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C\1 ISHXLNHNDMZNMC-VTKCIJPMSA-N 0.000 abstract 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 abstract 1
- 230000021736 acetylation Effects 0.000 abstract 1
- 238000006640 acetylation reaction Methods 0.000 abstract 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 abstract 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 abstract 1
- HQQUTGFAWJNQIP-UHFFFAOYSA-K aluminum;diacetate;hydroxide Chemical compound CC(=O)O[Al](O)OC(C)=O HQQUTGFAWJNQIP-UHFFFAOYSA-K 0.000 abstract 1
- IDOSCGGXFAKNLS-UHFFFAOYSA-K aluminum;dichloride;hydroxide Chemical compound [Cl-].[Cl-].[Al+2]O IDOSCGGXFAKNLS-UHFFFAOYSA-K 0.000 abstract 1
- 239000012298 atmosphere Substances 0.000 abstract 1
- 239000006227 byproduct Substances 0.000 abstract 1
- 239000012043 crude product Substances 0.000 abstract 1
- -1 enol acetate Chemical class 0.000 abstract 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 abstract 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 abstract 1
- 239000005457 ice water Substances 0.000 abstract 1
- 239000011261 inert gas Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 239000012299 nitrogen atmosphere Substances 0.000 abstract 1
- 229960002667 norelgestromin Drugs 0.000 abstract 1
- 230000003647 oxidation Effects 0.000 abstract 1
- 238000007254 oxidation reaction Methods 0.000 abstract 1
- 125000004043 oxo group Chemical group O=* 0.000 abstract 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 239000000741 silica gel Substances 0.000 abstract 1
- 229910002027 silica gel Inorganic materials 0.000 abstract 1
- 239000001632 sodium acetate Substances 0.000 abstract 1
- 235000017281 sodium acetate Nutrition 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- 239000000725 suspension Substances 0.000 abstract 1
- 235000005074 zinc chloride Nutrition 0.000 abstract 1
- 239000011592 zinc chloride Substances 0.000 abstract 1
Classifications
-
- 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
- C07J41/0016—Oximes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0081—Substituted in position 17 alfa and 17 beta
- C07J1/0088—Substituted in position 17 alfa and 17 beta the substituent in position 17 alfa being an unsaturated hydrocarbon group
- C07J1/0096—Alkynyl derivatives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
Abstract
"PROCESSO PARA A SìNTESE DE D-(17<244>)-13-ETIL-17-HIDROXI-18,19-DINORPREGN-4-ENO-2 0-INO-3-ONA-OXIMA DE PUREZA ELEVADA". A invenção refere-se a um processo para a síntese de d-(17<244>)-13-etil-17-hidroxi-18,19-dinorpregn-4-eno-20-ino-3ona-o xima de pureza elevada (doravante norelgestromina) através da acetilação de d-norgestrel na posição 17, oximação do grupo de oxo na posição 3 do derivado de 17-acetoxi obtido e, finalmente, hidrolisação do grupo de acetoxi na posição 17 do derivado de 3-oxima obtido. O processo de acordo com a nossa invenção é como segue: o material de partida, d-(17<244>)-17-hidroxi-13-etil-18,19-dinorpregn-4-eno-20-ino-3-ona (d-norgestrel) - pureza de 93-94% - é acetilada com anidrido acético em ácido acético, na presença de cloreto de zinco e cloreto de hidrogênio, ou ácido perclórico a 70% em uma atmosfera de gás inerte, e depois do término da reação o excesso de anidrido acético e o subproduto de 'enol acetato' são decompostos com ácido hidroclórico aquosos, em seguida a d-(17<244>)-17-acetoxi-13-etil-18,19-dinorpregn-4-eno-20-ino-3-ona é isolada da mistura de reação por adição de água gelada, o produto precipitado é filtrado, lavado com água, seco, dissolvido em diclorometano ou acetona e clarificado com sílica gel ou óxido de alumínio e carvão vegetal, depois da filtração do clarificado a solução resultante é concentrada e o resíduo é recristalizado, a d-(17<244>)-17-acetoxi-13-etil-18,19-dinorpregn-4-eno-20-ino-3-ona obtida é reagida tanto com acetato de hidroxialumínio ou com cloreto de hidroxialumínio na presença de acetato de sódio, em ácido acético em atmosfera de nitrogênio sob agitação vigorosa durante aproximadamente 1 hora, após o término da reação é adicionada água, o produto precipitado é filtrado, lavado com água, seco e recristalizado, a d-(17<244>)-17-acetoxi-13-etil-18,19-dinorpregn-4-eno-20-ino-3-ona -oxima obtida é hidrolisada com uma quantidade equivalente de um hidróxido de metal alcalino em uma solução de alcanol de C~ 1~-C~ 4~, em atmosfera de nitrogênio entre uma temperatura de aproximadamente 5-38<198>C, sob agitação vigorosa, após o término da reação a mistura é diluída com água e o pH da suspensão resultante é ajustado para 7,5-9 com ácido acético, o produto precipitado é filtrado, lavado com água, seco e o produto cru é dissolvido em etanol, clarificado com carvão vegetal e após filtração do clarificado é adicionada água à solução obtida, a d-(17<244>)-17-acetoxi-13-etil-18,19-dinorpregn-4-eno-20-ino-3-ona -oxima precipitada de pureza elevada é filtrada, lavada com água e em dados casos recristalizada a partir de etanol.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU0301982A HUP0301982A2 (hu) | 2003-06-30 | 2003-06-30 | Eljárás nagy tisztaságú d-(17alfa)-13-etil-17-hidroxi-18,19-dinor-pregn-4-én-20-in-3-on-oxim előállítására |
| PCT/HU2004/000031 WO2005000868A1 (en) | 2003-06-30 | 2004-04-29 | Process for the synthesis of high purity d-(17alpha)-13-ethyl-17hydroxy-18,19-dinorpre:gn-4-ene-20-yne-3-one-oxime |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0412186A true BRPI0412186A (pt) | 2006-08-22 |
Family
ID=90001694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0412186-4A BRPI0412186A (pt) | 2003-06-30 | 2004-04-29 | processo para a sìntese de d-(17alfa)-13-etil-17-hidroxi-18,19-dinorpregn-4-eno-20-i no-3-ona-oxima de pureza elevada |
Country Status (17)
| Country | Link |
|---|---|
| EP (1) | EP1638988B1 (pt) |
| JP (1) | JP2007516946A (pt) |
| CN (1) | CN100355771C (pt) |
| AT (1) | ATE462712T1 (pt) |
| AU (1) | AU2004251118A1 (pt) |
| BR (1) | BRPI0412186A (pt) |
| CA (1) | CA2528952A1 (pt) |
| DE (1) | DE602004026306D1 (pt) |
| EA (1) | EA008411B1 (pt) |
| HR (1) | HRP20060038A2 (pt) |
| HU (1) | HUP0301982A2 (pt) |
| MX (1) | MXPA05013948A (pt) |
| NO (1) | NO20060455L (pt) |
| NZ (1) | NZ544378A (pt) |
| RS (1) | RS20050897A (pt) |
| UA (1) | UA80059C2 (pt) |
| WO (1) | WO2005000868A1 (pt) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7576226B2 (en) | 2003-06-30 | 2009-08-18 | Richter Gedeon Vegyeszeti Gyar Rt. | Process of making isomers of norelgestromin and methods using the same |
| ITMI20052464A1 (it) * | 2005-12-22 | 2007-06-23 | S N I F F Italia S P A | Procedimento per la preparazi9one di norelgestromin norelgestromina |
| CN108827950B (zh) * | 2018-05-31 | 2020-08-21 | 成都市科隆化学品有限公司 | 乙酸中微量乙酸酐的检测方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL7306609A (pt) * | 1972-05-26 | 1973-11-28 | ||
| US4027019A (en) * | 1975-07-24 | 1977-05-31 | Ortho Pharmaceutical Corporation | 3-Oximes of D-17α-ethynyl-19-nortestosterone esters and method |
| CN1188189C (zh) * | 1995-06-07 | 2005-02-09 | 奥瑟－麦内尔制药公司 | 基质层含有17－脱乙酰基诺孕酯的经皮贴片及基质的用途 |
-
2003
- 2003-06-30 HU HU0301982A patent/HUP0301982A2/hu unknown
-
2004
- 2004-04-29 UA UAA200600812A patent/UA80059C2/uk unknown
- 2004-04-29 DE DE602004026306T patent/DE602004026306D1/de not_active Expired - Fee Related
- 2004-04-29 NZ NZ544378A patent/NZ544378A/en unknown
- 2004-04-29 AU AU2004251118A patent/AU2004251118A1/en not_active Abandoned
- 2004-04-29 WO PCT/HU2004/000031 patent/WO2005000868A1/en active Application Filing
- 2004-04-29 JP JP2006518378A patent/JP2007516946A/ja active Pending
- 2004-04-29 CA CA002528952A patent/CA2528952A1/en not_active Abandoned
- 2004-04-29 BR BRPI0412186-4A patent/BRPI0412186A/pt not_active IP Right Cessation
- 2004-04-29 RS YUP-2005/0897A patent/RS20050897A/sr unknown
- 2004-04-29 EP EP04730316A patent/EP1638988B1/en not_active Expired - Lifetime
- 2004-04-29 MX MXPA05013948A patent/MXPA05013948A/es active IP Right Grant
- 2004-04-29 AT AT04730316T patent/ATE462712T1/de not_active IP Right Cessation
- 2004-04-29 EA EA200600119A patent/EA008411B1/ru not_active IP Right Cessation
- 2004-04-29 CN CNB2004800165780A patent/CN100355771C/zh not_active Expired - Fee Related
-
2006
- 2006-01-27 NO NO20060455A patent/NO20060455L/no not_active Application Discontinuation
- 2006-01-27 HR HR20060038A patent/HRP20060038A2/xx not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2528952A1 (en) | 2005-01-06 |
| CN100355771C (zh) | 2007-12-19 |
| DE602004026306D1 (de) | 2010-05-12 |
| WO2005000868A1 (en) | 2005-01-06 |
| RS20050897A (sr) | 2007-08-03 |
| NO20060455L (no) | 2006-03-29 |
| EP1638988A1 (en) | 2006-03-29 |
| UA80059C2 (en) | 2007-08-10 |
| HUP0301982D0 (en) | 2003-09-29 |
| HRP20060038A2 (en) | 2006-11-30 |
| EA008411B1 (ru) | 2007-04-27 |
| CN1805970A (zh) | 2006-07-19 |
| AU2004251118A1 (en) | 2005-01-06 |
| NZ544378A (en) | 2008-02-29 |
| EP1638988B1 (en) | 2010-03-31 |
| ATE462712T1 (de) | 2010-04-15 |
| EA200600119A1 (ru) | 2006-06-30 |
| JP2007516946A (ja) | 2007-06-28 |
| MXPA05013948A (es) | 2006-03-09 |
| HUP0301982A2 (hu) | 2005-04-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BR112014010263B1 (pt) | Método de preparação do acetato de ulipristal e intermediário deste | |
| GB2480632A (en) | Preparation of 12-keto and 12-alpha-hydroxy steroids | |
| US20080125407A1 (en) | Method for preparation of fluticasone propionate | |
| JPS5842878B2 (ja) | １２−オキソコラン酸トシルヒドラゾン化合物、その製法ならびに利用 | |
| CA3190433A1 (en) | Methods of making cholic acid derivatives and starting materials therefor | |
| ES2198520T3 (es) | Procedimiento para preparar reina y diacereina. | |
| PT825197E (pt) | Novos derivados de 6-hidroxi e 6-oxo-androstano com actividade sobre o sistema cardiovascular e composicoes farmaceuticas que os contem | |
| EP2247573B1 (en) | Carbonic and sulphuric acid salts of 3-(2,2,2-trimethylhydrazinium)propionate esters and their use for 3-(2,2,2-trimethylhydrazinium)propionate dihydrate preparation | |
| BRPI0412186A (pt) | processo para a sìntese de d-(17alfa)-13-etil-17-hidroxi-18,19-dinorpregn-4-eno-20-i no-3-ona-oxima de pureza elevada | |
| EP1385867B1 (en) | Preparation of bile acids | |
| HU198739B (en) | New process for producing 4-aminoandrostenedione derivative | |
| US6653492B2 (en) | Preparation of bile acids | |
| SATO et al. | The Chemistry of the Spiroaminoketal Side Chain of Solasodine and Tomatidine. I. 1 Improved Preparation of 3β-Acetoxy-5, 16-pregnadien-20-one and 3β-Acetoxy-5α-pregn-16-en-20-one from Solasodine and Tomatidine. | |
| UNDHEIM et al. | iV-Quaternary Compounds | |
| US2615902A (en) | Chemical compounds and processes for preparing the same | |
| Wolfrom et al. | Amino Derivatives of Starches. Derivatives of 3, 6-Diamino-3, 6-dideoxy-D-altrose1, 2 | |
| ONODERA et al. | N-acylation of unsubstituted glycosylamines | |
| JP2007516946A5 (pt) | ||
| JPH10507451A (ja) | ６−アザアンドロステノンの合成 | |
| US20080234478A1 (en) | Process for the preparation and purification of eplerenone | |
| US3890304A (en) | 7{60 -carbam oyl-17-hydroxy-3-oxo-17{60 -pregn-4-ene-21-carboxylic acid {65 -lactone and related compounds | |
| JP2013119518A (ja) | （ｓ）−２−ベンジル―３−（シス−ヘキサヒドロ−２−イソインドリニルカルボニル）プロピオン酸ベンジルの製造方法 | |
| JPH06501272A (ja) | １７β−置換−４−アザ−５α−アンドロスタン−３−オン誘導体の製法 | |
| EP1669355A1 (en) | Aminotetrahydropteridines and processes for manufacture thereof | |
| US3542862A (en) | 3-(o-aroylaminophenyl)-levulinic acids |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B08F | Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette] |
Free format text: REFERENTE A 7A ANUIDADE(S) |
|
| B08K | Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette] |
Free format text: REFERENTE AO DESPACHO 8.6 PUBLICADO NA RPI 2129 DE 25/10/2011. |