AR097878A1 - Proceso industrial para la síntesis de ingredientes activos esteroides - Google Patents
Proceso industrial para la síntesis de ingredientes activos esteroidesInfo
- Publication number
- AR097878A1 AR097878A1 ARP140103652A ARP140103652A AR097878A1 AR 097878 A1 AR097878 A1 AR 097878A1 AR P140103652 A ARP140103652 A AR P140103652A AR P140103652 A ARP140103652 A AR P140103652A AR 097878 A1 AR097878 A1 AR 097878A1
- Authority
- AR
- Argentina
- Prior art keywords
- formula
- compound
- meaning
- temperature
- dimethylamino
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title abstract 2
- 238000003786 synthesis reaction Methods 0.000 title abstract 2
- 239000004480 active ingredient Substances 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000003431 steroids Chemical class 0.000 title 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract 9
- 150000001875 compounds Chemical class 0.000 abstract 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 abstract 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 abstract 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 abstract 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 abstract 5
- 239000002904 solvent Substances 0.000 abstract 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 abstract 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 abstract 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract 3
- UIOAQJNADLELPQ-UHFFFAOYSA-N C[C]1OCCO1 Chemical group C[C]1OCCO1 UIOAQJNADLELPQ-UHFFFAOYSA-N 0.000 abstract 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 abstract 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 abstract 2
- 238000009835 boiling Methods 0.000 abstract 2
- 150000002466 imines Chemical class 0.000 abstract 2
- 229910052500 inorganic mineral Inorganic materials 0.000 abstract 2
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 abstract 2
- 239000011707 mineral Substances 0.000 abstract 2
- 150000007522 mineralic acids Chemical class 0.000 abstract 2
- 239000000203 mixture Substances 0.000 abstract 2
- 150000007524 organic acids Chemical class 0.000 abstract 2
- 239000003960 organic solvent Substances 0.000 abstract 2
- AZFVLHQDIIJLJG-UHFFFAOYSA-N chloromethylsilane Chemical compound [SiH3]CCl AZFVLHQDIIJLJG-UHFFFAOYSA-N 0.000 abstract 1
- 150000004985 diamines Chemical class 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract 1
Classifications
-
- 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
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- 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
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
-
- 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
- C07J75/00—Processes for the preparation of steroids in general
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Endocrinology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Abstract
Se reivindica el compuesto de fórmula (3). Reivindicación 1: Un proceso para la síntesis del compuesto de fórmula (1) (donde el significado de R es grupo dimetilamino o acetilo) caracterizado porque a) el compuesto de fórmula (2) (donde el significado de R es grupo dimetilamino o 2-metil-1,3-dioxolan-2-ilo) se hace reaccionar con 2 - 15 equivalentes molares de metil-litio en presencia de tetraalquiletilendiamina en solvente de tipo acetal éter o formaldehído o en una mezcla de los mismos a una temperatura entre -78 - (-20)ºC, luego la imina protegida obtenida como intermediario se hace reaccionar con un ácido mineral u orgánico fuerte a una temperatura entre 0ºC y el punto de ebullición del solvente orgánico usado, luego el grupo hidroxilo en la posición 17 del compuesto de fórmula (4) obtenido (donde el significado de R es como se describe para la fórmula (1)) se acetila con anhídrido acético en un solvente halogenado, preferentemente diclorometano, en presencia de ácido perclórico 70% a una temperatura entre -78 - 0ºC, luego el compuesto de fórmula (1) obtenido (donde el significado de R es grupo dimetilamino o acetilo) en este caso se recristaliza desde metanol o etanol; o b) el grupo hidroxilo en la posición 5 del compuesto de fórmula (2) (donde el significado de R es grupo dimetilamino o 2-metil-1,3-dioxolan-2-ilo) se silila con clorometilsilano en presencia de imidazol en un solvente halogenado, tetrahidrofurano o tolueno, preferentemente en diclorometano a temperatura ambiente; luego el compuesto obtenido de fórmula (3) (donde el significado de R es como se describe para la fórmula (2)) se hace reaccionar con 2 - 15 equivalentes molares de metil-litio en presencia de tetraalquiletilendiamina en un solvente de tipo acetal éter o formaldehído o en una mezcla de los mismos a una temperatura entre -78 - (-20)ºC, luego la imina protegida obtenida como intermediario se hace reaccionar con un ácido mineral u orgánico fuerte a una temperatura entre 0ºC y el punto de ebullición del solvente orgánico usado, luego el grupo hidroxilo en la posición 17 del compuesto de fórmula (4) obtenido (donde el significado de R es como se describe para la fórmula (1)) se acetila con anhídrido acético en un solvente halogenado, preferentemente diclorometano, en presencia de ácido perclórico 70% a una temperatura entre -78 - 0ºC, luego el compuesto de fórmula (1) obtenido (donde el significado de R es grupo dimetilamino o acetilo) en este caso se recristaliza desde metanol o etanol.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU1300566A HU230319B1 (hu) | 2013-10-01 | 2013-10-01 | Ipari eljárás szteroid hatóanyagok előállítására |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR097878A1 true AR097878A1 (es) | 2016-04-20 |
Family
ID=89991273
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP140103652A AR097878A1 (es) | 2013-10-01 | 2014-10-01 | Proceso industrial para la síntesis de ingredientes activos esteroides |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US9676814B2 (es) |
| EP (1) | EP3052513B1 (es) |
| JP (1) | JP6796366B2 (es) |
| KR (1) | KR20160062046A (es) |
| CN (1) | CN105593236B (es) |
| AR (1) | AR097878A1 (es) |
| AU (1) | AU2014330860B2 (es) |
| BR (1) | BR112016006979B1 (es) |
| CA (1) | CA2924553C (es) |
| CY (1) | CY1121286T1 (es) |
| DK (1) | DK3052513T3 (es) |
| EA (1) | EA030905B1 (es) |
| ES (1) | ES2713325T3 (es) |
| HK (1) | HK1223105A1 (es) |
| HR (1) | HRP20190414T1 (es) |
| HU (2) | HU230319B1 (es) |
| IL (1) | IL244501A0 (es) |
| LT (1) | LT3052513T (es) |
| ME (1) | ME03337B (es) |
| MX (1) | MX355222B (es) |
| MY (1) | MY176613A (es) |
| PL (1) | PL3052513T3 (es) |
| PT (1) | PT3052513T (es) |
| RS (1) | RS58252B1 (es) |
| SG (1) | SG11201601683SA (es) |
| SI (1) | SI3052513T1 (es) |
| TR (1) | TR201901381T4 (es) |
| UA (1) | UA118269C2 (es) |
| UY (1) | UY35766A (es) |
| WO (1) | WO2015049637A1 (es) |
| ZA (1) | ZA201601589B (es) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU230381B1 (hu) * | 2014-02-17 | 2016-03-29 | Richter Gedeon Nyrt | Ipari eljárás szteroid intermedier előállítására |
| 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 |
| CN112461957B (zh) * | 2020-11-12 | 2022-02-22 | 湖南新合新生物医药有限公司 | 一种检测醋酸乌利司他中间体ii中杂质含量的方法 |
| CN112578037A (zh) * | 2020-11-12 | 2021-03-30 | 湖南新合新生物医药有限公司 | 一种检测醋酸乌利司他中间体ⅰ中乌双缩酮含量的方法 |
Family Cites Families (11)
| 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 |
| DK0900234T3 (da) * | 1996-05-01 | 2000-11-06 | Us Gov Health & Human Serv | 21-substituerede progesteronderivater anvendt som nye antigestagener |
| US6020328A (en) * | 1998-03-06 | 2000-02-01 | Research Triangle Institute | 20-keto-11β-arylsteroids and their derivatives having agonist or antagonist hormonal properties |
| CA2403756C (en) * | 2000-03-17 | 2010-02-09 | Hyun K. Kim | Structural modification of 19-norprogesterone i: 17-.alpha.-substituted, 11-.beta.-substituted-4-aryl and 21-substituted 19-norpregnadienedione as new antiprogestational agents |
| AU2004217988C1 (en) * | 2003-02-28 | 2010-06-03 | Southwest Foundation For Biomedical Research | Method for preparing 17 alpha-acetoxy-11beta-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione, intermediates thereof, and methods for the preparation of such intermediates |
| HU227112B1 (hu) | 2006-06-14 | 2010-07-28 | Richter Gedeon Nyrt | 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 |
| HU228636B1 (en) | 2007-06-27 | 2013-04-29 | Richter Gedeon Nyrt | Industrial method for the synthesis of 17-acetoxy-11betha-4[-(dimethylamino)-phenyl]-21-methoxy-19-norpregna-4,9-dien-3,20-dione and the key intermediates of the process |
| 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 |
| 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 |
-
2013
- 2013-10-01 HU HU1300566A patent/HU230319B1/hu not_active IP Right Cessation
-
2014
- 2014-10-01 PL PL14790731T patent/PL3052513T3/pl unknown
- 2014-10-01 KR KR1020167009887A patent/KR20160062046A/ko not_active Application Discontinuation
- 2014-10-01 MY MYPI2016700818A patent/MY176613A/en unknown
- 2014-10-01 AU AU2014330860A patent/AU2014330860B2/en active Active
- 2014-10-01 UY UY0001035766A patent/UY35766A/es not_active Application Discontinuation
- 2014-10-01 JP JP2016519337A patent/JP6796366B2/ja active Active
- 2014-10-01 US US15/024,822 patent/US9676814B2/en active Active
- 2014-10-01 EA EA201690467A patent/EA030905B1/ru unknown
- 2014-10-01 ES ES14790731T patent/ES2713325T3/es active Active
- 2014-10-01 SG SG11201601683SA patent/SG11201601683SA/en unknown
- 2014-10-01 EP EP14790731.5A patent/EP3052513B1/en active Active
- 2014-10-01 MX MX2016004263A patent/MX355222B/es active IP Right Grant
- 2014-10-01 SI SI201431081T patent/SI3052513T1/sl unknown
- 2014-10-01 CA CA2924553A patent/CA2924553C/en active Active
- 2014-10-01 CN CN201480054468.7A patent/CN105593236B/zh active Active
- 2014-10-01 PT PT14790731T patent/PT3052513T/pt unknown
- 2014-10-01 AR ARP140103652A patent/AR097878A1/es not_active Application Discontinuation
- 2014-10-01 RS RS20190130A patent/RS58252B1/sr unknown
- 2014-10-01 ME MEP-2019-56A patent/ME03337B/me unknown
- 2014-10-01 LT LTEP14790731.5T patent/LT3052513T/lt unknown
- 2014-10-01 WO PCT/IB2014/064979 patent/WO2015049637A1/en active Application Filing
- 2014-10-01 UA UAA201604876A patent/UA118269C2/uk unknown
- 2014-10-01 TR TR2019/01381T patent/TR201901381T4/tr unknown
- 2014-10-01 DK DK14790731.5T patent/DK3052513T3/en active
- 2014-10-01 BR BR112016006979-0A patent/BR112016006979B1/pt not_active IP Right Cessation
- 2014-10-01 HU HUE14790731A patent/HUE043002T2/hu unknown
-
2016
- 2016-03-07 ZA ZA2016/01589A patent/ZA201601589B/en unknown
- 2016-03-08 IL IL244501A patent/IL244501A0/en active IP Right Grant
- 2016-09-23 HK HK16111226.5A patent/HK1223105A1/zh unknown
-
2019
- 2019-02-27 CY CY20191100243T patent/CY1121286T1/el unknown
- 2019-03-04 HR HRP20190414TT patent/HRP20190414T1/hr unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AR097878A1 (es) | Proceso industrial para la síntesis de ingredientes activos esteroides | |
| SV2016005149A (es) | Polimorfo de los inhibidores de la syk | |
| SV2016005312A (es) | Compuestos de imidazo[4,5-c]quinolin-2-ona y su uso para tratar cã�ncer | |
| CO6721004A2 (es) | Polímero fabricado a partir de ácido maleico, éter de alilo y acetato de vinilo y la preparación y uso de dicho polímero | |
| UY31774A (es) | Compuestos de 2-pirimidin-5- ilcarboxamida sustituidos | |
| BRPI0613429A2 (pt) | inibidores de histona desacetilase | |
| UA109883C2 (uk) | Спосіб отримання сполук для застосування як інгібіторів sglt2 | |
| EA201591503A1 (ru) | Производные нафтиридина, полезные в качестве антагонистов альфа-v-бета-6 интегрина | |
| ECSP10010722A (es) | Compuestos orgánicos | |
| MX2015000755A (es) | Dispositivo de tratamiento para inodoro. | |
| AR091651A1 (es) | Elaboracion de acido 2-(5-bromo-4-(4-ciclopropilnaftalen-1-il)-4h-1,2,4-triazol-3-iltio)acetico | |
| CR20120334A (es) | Derivados de imidazopiridina como inhibidores de jak | |
| ECSP099571A (es) | Derivados pirazólicos como inhibidores de la 11-beta-hsd1 | |
| BR112014012358A2 (pt) | 2-oxo-1,3-dioxolano-4-carboxamidas, sua preparação e uso | |
| PE20190172A1 (es) | Sintesis de indazoles | |
| EA201101099A1 (ru) | Гербициды, полученные из циклопентадиона | |
| AR061151A1 (es) | Formas cristalinas de 11beta - (4 - acetilfenil) - 20, 20, 21, 21, 21 - pentafluoro - 17 - hidroxi - 19 - nor - 17alfa - pregna - 4, 9 - dien - 3 - ona, metodos para su obtencion y preparaciones farmaceuticas que las contienen para emplear en el tratamiento de miomas y cancer de mamas. | |
| CR20170134A (es) | Método para preparar 2´-o-fucosil-lactosa | |
| AR095059A1 (es) | Compuestos herbicidas | |
| MX2015017536A (es) | Alquilacion con un alquil sulfonato de fluoroalquilo. | |
| HN2011003005A (es) | [1,2,4] triazolo [4,3-b] piridazinas como ligandos del receptor de androgenos. | |
| UY28911A1 (es) | Profármacos de esteroides con acción androgénica | |
| CO6680619A2 (es) | Formulaciones | |
| AR098524A1 (es) | PROCESO PARA LA SÍNTESIS DE (11b,17a)-17-ACETOXI-11-METIL-3-OXO-NORPREGN-4-ENO | |
| CL2008003086A1 (es) | Proceso para preparar 2-(fenilo sustituido-2-hidroxi-etil) carbamatos por reduccion de un alfa-alcohol ester protegido. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FC | Refusal |