HRP20140668T1 - Postupak proizvodnje prasugrel hidroklorida visoke äśistoä†e - Google Patents
Postupak proizvodnje prasugrel hidroklorida visoke äśistoä†e Download PDFInfo
- Publication number
- HRP20140668T1 HRP20140668T1 HRP20140668AT HRP20140668T HRP20140668T1 HR P20140668 T1 HRP20140668 T1 HR P20140668T1 HR P20140668A T HRP20140668A T HR P20140668AT HR P20140668 T HRP20140668 T HR P20140668T HR P20140668 T1 HRP20140668 T1 HR P20140668T1
- Authority
- HR
- Croatia
- Prior art keywords
- process according
- compound represented
- chlorinating agent
- image
- reaction
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 17
- JALHGCPDPSNJNY-UHFFFAOYSA-N [5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-6,7-dihydro-4h-thieno[3,2-c]pyridin-2-yl] acetate;hydron;chloride Chemical compound Cl.C1CC=2SC(OC(=O)C)=CC=2CN1C(C=1C(=CC=CC=1)F)C(=O)C1CC1 JALHGCPDPSNJNY-UHFFFAOYSA-N 0.000 title claims 3
- 229960004947 prasugrel hydrochloride Drugs 0.000 title claims 3
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 239000012320 chlorinating reagent Substances 0.000 claims 9
- 238000006243 chemical reaction Methods 0.000 claims 8
- 150000001875 compounds Chemical class 0.000 claims 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 4
- 239000002904 solvent Substances 0.000 claims 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical group CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- 239000012345 acetylating agent Substances 0.000 claims 2
- 230000021736 acetylation Effects 0.000 claims 2
- 238000006640 acetylation reaction Methods 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- 238000005660 chlorination reaction Methods 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 150000002825 nitriles Chemical class 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Claims (16)
1. Postupak proizvodnje prasugrel hidroklorida, obuhvaća korake:
(i) kloriranje spoja predstavljenog formulom:
[image]
tako što mu se dodaje sredstvo za kloriranje u otapalu;
(ii) reakcija dobivenog spoja predstavljenog formulom:
[image]
sa spojem predstavljenim općom formulom:
[image]
gdje R predstavlja zaštitnu skupinu za hidroksilnu skupinu,
ili njegovom soli u otapalu u prisutnosti baze;
(iii) acetiliranje dobivenog spoja predstavljenog općom formulom:
[image]
gdje R ima jednako značenje kako je gore navedeno,
njegovom reakcijom sa sredstvom za acetiliranje u otapalu u prisutnosti baze i katalizatorom acetiliranja, i
(iv) dodavanje klorovodične kiseline u dobiveni spoj predstavljen formulom:
[image]
u otapalu, pri čemu se dobiva prasugrel hidroklorid predstavljen formulom:
[image]
naznačen time što je u koraku (i) temperatura za vrijeme dodavanja sredstva za kloriranje -20°C do 5°C i reakcijska temperatura nakon dodavanja sredstva za kloriranje je -20°C do 5°C.
2. Postupak prema zahtjevu 1, naznačen time što je u koraku (i) temperatura za vrijeme dodavanja sredstva za kloriranje -10°C do 5°C i reakcijska temperatura nakon dodavanja sredstva za kloriranje je -10°C do 5°C.
3. Postupak prema zahtjevu 1, naznačen time što je u koraku (i) temperatura za vrijeme dodavanja sredstva za kloriranje -5°C do 5°C i reakcijska temperatura nakon dodavanja sredstva za kloriranje je -5°C do 5°C.
4. Postupak prema bilo kojem od zahtjeva 1 do 3, naznačen time što se sredstvo za kloriranje dodaje u kapima.
5. Postupak prema bilo kojem od zahtjeva 1 do 4, naznačen time što se klorovodična kiselina dodaje u kapima.
6. Postupak prema bilo kojem od zahtjeva 1 do 5, naznačen time što je temperatura naknadne obrade nakon kraja reakcije u koraku (i) -20°C do 15°C.
7. Postupak prema bilo kojem od zahtjeva 1 do 5, naznačen time što je temperatura naknadne obrade nakon kraja reakcije u koraku (i) -10°C do 15°C.
8. Postupak prema bilo kojem od zahtjeva 1 do 5, naznačen time što je temperatura naknadne obrade nakon kraja reakcije u koraku (i) 0°C do 15°C.
9. Postupak prema bilo kojem od zahtjeva 1 do 5, gdje je sredstvo za kloriranje plinoviti klor.
10. Postupak prema bilo kojem od zahtjeva 1 do 9, gdje je R skupina predstavljena općom formulom:
[image]
gdje R1, R2 i R3 nezavisno predstavljaju alkilnu skupinu s 1 do 10 ugljika ili arilnu skupinu.
11. Postupak prema zahtjevu 10, gdje R1, R2 i R3 nezavisno predstavljaju alkilnu skupinu s 1 do 5 ugljika ili fenil.
12. Postupak prema bilo kojem od zahtjeva 1 do 9, gdje je R tert-butildimetilsilil.
13. Postupak prema bilo kojem od zahtjeva 1 do 12, naznačen time što se dobiveni spoj predstavljen općom formulom (II) rekristalizira iz etera ili nitrila u koraku (ii).
14. Postupak prema bilo kojem od zahtjeva 1 do 12, naznačen time što se dobiveni spoj predstavljen općom formulom (II) rekristalizira iz acetonitrila u koraku (ii).
15. Postupak prema bilo kojem od zahtjeva 1 do 14, gdje sredstvo za acetiliranje anhidrid octene kiseline.
16. Postupak prema bilo kojem od zahtjeva 1 do 15, naznačen time što se dobiveni spoj predstavljen formulom (I) dobiven u koraku (iii) koristi u sljedećem koraku (iv) bez pročišćavanja.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2007053093 | 2007-03-02 | ||
| PCT/JP2008/053617 WO2008108291A1 (ja) | 2007-03-02 | 2008-02-29 | 高純度のプラスグレル塩酸塩の製造方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20140668T1 true HRP20140668T1 (hr) | 2014-10-10 |
Family
ID=39738173
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20140668AT HRP20140668T1 (hr) | 2007-03-02 | 2014-07-14 | Postupak proizvodnje prasugrel hidroklorida visoke äśistoä†e |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US20100094013A1 (hr) |
| EP (1) | EP2123656B1 (hr) |
| JP (1) | JP5363307B2 (hr) |
| KR (1) | KR101505212B1 (hr) |
| CN (2) | CN101675058A (hr) |
| AU (1) | AU2008222000B2 (hr) |
| BR (1) | BRPI0808034A2 (hr) |
| CA (1) | CA2679925C (hr) |
| CO (1) | CO6210821A2 (hr) |
| CY (1) | CY1115518T1 (hr) |
| DK (1) | DK2123656T3 (hr) |
| ES (1) | ES2487190T3 (hr) |
| HK (1) | HK1136278A1 (hr) |
| HR (1) | HRP20140668T1 (hr) |
| IL (1) | IL200647A (hr) |
| MX (1) | MX2009009413A (hr) |
| MY (1) | MY151726A (hr) |
| NZ (1) | NZ579993A (hr) |
| PL (1) | PL2123656T3 (hr) |
| PT (1) | PT2123656E (hr) |
| RU (1) | RU2435776C2 (hr) |
| SI (1) | SI2123656T1 (hr) |
| TW (1) | TWI417295B (hr) |
| WO (1) | WO2008108291A1 (hr) |
| ZA (1) | ZA200906850B (hr) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2009011619A (es) | 2007-04-27 | 2010-01-18 | Cydex Pharmaceuticals Inc | Formulaciones que contienen clopidogrel y eter sulfoalquilico-ciclodextrina y metodos de uso. |
| WO2009062044A2 (en) * | 2007-11-09 | 2009-05-14 | Dr. Reddy's Laboratories Ltd. | Processes for the preparation of prasugrel, and its salts and polymorphs |
| CN103936756B (zh) * | 2008-09-22 | 2017-09-19 | 广州赫尔氏药物开发有限公司 | 具有抗凝血作用的化合物 |
| CN101684124B (zh) * | 2008-09-22 | 2013-11-13 | 广州赫尔氏药物开发有限公司 | 新的具有抗凝血作用的化合物 |
| CN101486635B (zh) * | 2009-02-27 | 2012-10-10 | 上海医药工业研究院 | α-环丙基羰基-2-氟苄基卤素的制备方法 |
| KR101912709B1 (ko) * | 2009-05-13 | 2018-10-30 | 사이덱스 파마슈티칼스, 인크. | 프라수그렐 및 사이클로덱스트린 유도체를 포함하는 약학 조성물 및 그의 제조 및 사용 방법 |
| CN101993447A (zh) * | 2009-08-26 | 2011-03-30 | 浙江华海药业股份有限公司 | 一种人工合成普拉格雷的方法 |
| HU229035B1 (en) | 2009-12-21 | 2013-07-29 | Egis Gyogyszergyar Nyilvanosan Muekoedoe Reszvenytarsasag | Process for producing prasurgel |
| HU229031B1 (en) | 2009-12-21 | 2013-07-29 | Egis Gyogyszergyar Nyilvanosan Muekoedoe Reszvenytarsasag | Process for producing prasurgel and its intermediate |
| CN101735241A (zh) * | 2009-12-24 | 2010-06-16 | 浙江普洛家园药业有限公司 | 普拉格雷中间体及其制备方法 |
| CN102869668A (zh) | 2010-03-09 | 2013-01-09 | 斯索恩有限公司 | 制备普拉格雷的方法 |
| EP2528924A1 (en) * | 2010-03-23 | 2012-12-05 | Alembic Pharmaceuticals Limited | A process for the preparation of prasugrel hcl salt |
| WO2012001486A1 (en) * | 2010-06-28 | 2012-01-05 | Mayuka Labs Pvt. Ltd. | An improved process for the preparation of prasugrel hydrochloride and its intermediates |
| WO2012018791A2 (en) * | 2010-08-06 | 2012-02-09 | Dr. Reddy's Laboratories Ltd. | Preparation of prasugrel hydrochloride |
| CN101948479B (zh) * | 2010-09-29 | 2013-01-30 | 横店集团家园化工有限公司 | 普拉格雷中间体及其制备方法 |
| HUP1000565A2 (en) | 2010-10-22 | 2012-05-02 | Egis Gyogyszergyar Nyrt | Process for the preparation of pharmaceutically active compound and intermediers |
| CN102101827B (zh) * | 2010-11-15 | 2013-07-03 | 山东新华制药股份有限公司 | 一种普拉格雷中间体α-环丙羰基-2-氟苄基卤的制备方法 |
| CN103517909B (zh) * | 2011-04-14 | 2015-04-08 | 广州赫尔氏药物开发有限公司 | 新型抗血小板化合物的加成盐 |
| CN102746318A (zh) * | 2011-04-20 | 2012-10-24 | 上海信谊药厂有限公司 | 用于制备普拉格雷盐酸盐的方法 |
| CN102276623A (zh) * | 2011-06-13 | 2011-12-14 | 安徽省虹升生物科技有限公司 | 一种利用有机硅保护剂进行制备普拉格雷的新方法 |
| CN102838618A (zh) * | 2011-06-22 | 2012-12-26 | 广东东阳光药业有限公司 | 一种制备普拉格雷的方法及普拉格雷盐酸盐新晶型 |
| WO2013024399A1 (en) * | 2011-08-12 | 2013-02-21 | Alembic Pharmaceuticals Limited | Improved method for quantitative determination of prasugrel hydrochloride |
| CN102977115B (zh) * | 2012-11-16 | 2015-01-21 | 江苏先声药业有限公司 | 普拉格雷游离碱的合成新方法 |
| CN105085541A (zh) * | 2014-05-07 | 2015-11-25 | 江苏先声药业有限公司 | 一种普拉格雷类似物的制备方法 |
| HU231079B1 (hu) | 2016-06-23 | 2020-06-29 | Richter Gedeon Nyrt. | Eljárás nagytisztaságú Prasugrel előállítására bromopentil szennyezés eltávolításával |
| CN112047959A (zh) * | 2020-10-21 | 2020-12-08 | 深圳市祥根生物科技有限公司 | 一种普拉格雷开环氯代杂质的制备方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI101150B (fi) * | 1991-09-09 | 1998-04-30 | Sankyo Co | Menetelmä lääkeaineina käyttökelpoisten tetrahydrotienopyridiinin johd annaisten valmistamiseksi |
| JP3840662B2 (ja) * | 1994-10-07 | 2006-11-01 | 宇部興産株式会社 | ２−シリルオキシ−テトラヒドロチエノピリジン類、その塩およびその製造方法 |
| KR20030014294A (ko) * | 2000-07-06 | 2003-02-15 | 상꾜 가부시키가이샤 | 히드로피리딘 유도체 산부가염 |
| JP4001199B2 (ja) * | 2000-07-06 | 2007-10-31 | 第一三共株式会社 | ヒドロピリジン誘導体酸付加塩 |
| SK287972B6 (sk) * | 2000-12-25 | 2012-08-06 | Daiichi Sankyo Company Limited | Pharmaceutical composition comprising 2-acetoxypyridine derivative and aspirin, kit comprising these compounds and use thereof |
| JP4029974B2 (ja) * | 2001-12-21 | 2008-01-09 | 第一三共株式会社 | ヒドロピリジン誘導体酸付加塩を含有する医薬 |
| EP1660183A2 (en) * | 2003-05-05 | 2006-05-31 | Eli Lilly and Company | Treating cardiovascular diseases with a compound of formula 1 (cs 747 - prasugrel; rn 150322-43-4) |
| TWI318571B (en) * | 2005-06-10 | 2009-12-21 | Lilly Co Eli | Formulation of a thienopyridine platelet aggregation inhibitor |
| TWI392681B (zh) * | 2006-04-06 | 2013-04-11 | Daiichi Sankyo Co Ltd | 高純度普拉格雷及其酸加成鹽之製法 |
-
2008
- 2008-02-29 BR BRPI0808034-8A2A patent/BRPI0808034A2/pt not_active Application Discontinuation
- 2008-02-29 EP EP08712139.8A patent/EP2123656B1/en active Active
- 2008-02-29 PT PT87121398T patent/PT2123656E/pt unknown
- 2008-02-29 MX MX2009009413A patent/MX2009009413A/es active IP Right Grant
- 2008-02-29 CN CN200880014554A patent/CN101675058A/zh active Pending
- 2008-02-29 NZ NZ579993A patent/NZ579993A/en not_active IP Right Cessation
- 2008-02-29 PL PL08712139T patent/PL2123656T3/pl unknown
- 2008-02-29 US US12/449,810 patent/US20100094013A1/en not_active Abandoned
- 2008-02-29 JP JP2009502556A patent/JP5363307B2/ja active Active
- 2008-02-29 CA CA2679925A patent/CA2679925C/en active Active
- 2008-02-29 RU RU2009136445/04A patent/RU2435776C2/ru active
- 2008-02-29 MY MYPI20093639 patent/MY151726A/en unknown
- 2008-02-29 SI SI200831267T patent/SI2123656T1/sl unknown
- 2008-02-29 DK DK08712139.8T patent/DK2123656T3/da active
- 2008-02-29 KR KR1020097018316A patent/KR101505212B1/ko active IP Right Grant
- 2008-02-29 TW TW097107016A patent/TWI417295B/zh active
- 2008-02-29 AU AU2008222000A patent/AU2008222000B2/en active Active
- 2008-02-29 CN CN2011103661430A patent/CN102424686A/zh active Pending
- 2008-02-29 ES ES08712139.8T patent/ES2487190T3/es active Active
- 2008-02-29 WO PCT/JP2008/053617 patent/WO2008108291A1/ja active Application Filing
-
2009
- 2009-08-31 IL IL200647A patent/IL200647A/en active IP Right Grant
- 2009-09-02 CO CO09093300A patent/CO6210821A2/es not_active Application Discontinuation
- 2009-10-01 ZA ZA200906850A patent/ZA200906850B/xx unknown
-
2010
- 2010-03-17 HK HK10102810.2A patent/HK1136278A1/xx unknown
-
2012
- 2012-12-06 US US13/706,548 patent/US20130345428A1/en not_active Abandoned
-
2014
- 2014-07-14 HR HRP20140668AT patent/HRP20140668T1/hr unknown
- 2014-09-02 CY CY20141100700T patent/CY1115518T1/el unknown
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