SI21463B - Postopek za pripravo heksahidro-furo/2,3-b/furan-3-ola - Google Patents
Postopek za pripravo heksahidro-furo/2,3-b/furan-3-ola Download PDFInfo
- Publication number
- SI21463B SI21463B SI200220026A SI200220026A SI21463B SI 21463 B SI21463 B SI 21463B SI 200220026 A SI200220026 A SI 200220026A SI 200220026 A SI200220026 A SI 200220026A SI 21463 B SI21463 B SI 21463B
- Authority
- SI
- Slovenia
- Prior art keywords
- formula
- process according
- alkyl
- aryl
- intermediates
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/20—Oxygen atoms
-
- 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
Abstract
Predloženi izum se nanaša na postopek za pripravo heksahidro-furo(2,3-b)furan-3-ola, kot tudi novih intermediatov za uporabo v navedenem postopku. Natančneje se izum nanaša na stereoselektivni postopek za pripravo heksahidro-furo(2,3-b)furan-3-ola in na postopek, ki je primeren za prenos na industrijsko merilo.
Claims (28)
1 SI 21463 B Patentni zahtevki 1. Postopek za sintezo heksahidro-furo[2,3-b]furan-3-ola s formulo (7), izhajajoč iz intermediata s formulo (1), kjer vsak P1 in P2 predstavlja neodvisno vodik, hidroksi-zaščitno skupino ali lahko skupaj tvorita vicinal-diolno zaščitno skupino, OP2 P10.
H pri čemer transformiramo navedeni intermediat s formulo (1) v nitrometanski derivat s formulo (3), kjer R1 predstavlja alkil, aril ali aralkil, R2 predstavlja vodik ali C(=0)0R3, R3 predstavlja alkil, aril ali aralkil, ali R3, če je prisoten, in R1 skupaj z atomi, na katere sta vezana, lahko tvorita 6- do 8-člensko ciklično skupino, kije lahko po izbiri substituirana z alkilom, aralkilom ali arilom, OP2 R2 P10. 'C00R1 3 N02 naknadno transformiramo navedeni nitrometanski derivat v tetrahidrofuranski derivat s formulo (6), kjer OR4 predstavlja alkoholat, HO L ^OH 0R4 in nato transformiramo intermediat s formulo (6) v heksahidro-furo[2,3-b]furan-3-ol s formulo (7) z intramolekulamo ciklizacijsko reakcijo. HO 0^0 7 2 SI 21463 B
2. Postopek po zahtevku 1, kjer intermediat s formulo (3) transfomiramo v intermediat s formulo (6) z uporabo Nef reakcije.
3. Postopek po zahtevku 1 ali 2 za sintezo heksahidro-furo[2,3-b]furan-3-ola s formulo (7), ki obsega stopnje: a) kondenziranje intermediata s formulo (1) OP2
kar ima za rezultat α,β-nenasičen ester s formulo (2), OP2 R2
b) reagiranje navedenega estra s formulo (2) z nitrometanom, kar ima za rezultat intermediat s formulo (3), OP2 R2 P10. COOR1 3 ^N02 c) izpostavitev navedenega intermediata s formulo (3) Nef reakciji, kar vodi do intermediatov s formulo (4) in (4')
d) transformiranje navedenih intermediatov s formulo (4) in (4') v intermediat s formulo (6) in SI 21463 B
HO
e) konverzijo intermediata s formulo (6) v spojino s formulo (7) z intramolekulamo ciklizacijsko reakcijo.
4. Postopek po kateremkoli od zahtevkov 1 do 3 za sintezo heksahidro-furo[2,3-b]furan-3-ola s formulo (7), ki obsega stopnje: a) kondenziranje intermediata s formulo (1) s CHR2R5-C(=0)-0R1, kjer R5 predstavlja vodik, karboksilni ester, fosfonijevo sol ali fosfonatni ester, OP2
kar ima za rezultat α,β-nenasičen ester s formulo (2) OP2 R2
b) reagiranje navedenega estra s formulo (2) z nitrometanom, kar ima za rezultat intermediat s formulo (3), OP2 R2
COOR1 >2 c) izpostavitev navedenega intermediata s formulo (3) Nef reakciji z obdelavo z bazo in naknadno z močno kislino, kar ima za rezultat zmes intermediatov s formulo (4) in (4*), 4 SI 21463 Β
Φ >-y le v primeru, ko je R drugačen od vodika, dekarboksiliranje intermediatov s formulo (4) in (4'), s čimer se tvorijo intermediati s formulo (5) oz. (5*)
e) redukcijo intermediatov s formulo (4) in (4') ali intermediatov s formulo (5) in (5’) z ustreznim redukcijskim sredstvom, kar ima za rezultat intermediat s formulo (6) in HO
OH f) konverzijo intermediata s formulo (6) v spojino s formulo (7) z intramolekulamo ciklizacijsko reakcijo.
5. Postopek po zahtevku 1 za sintezo heksahidro-furo[2,3-b]furan-3-ola s formulo (7.1) izhajajoč iz intermediata s formulo (1), kjer P1 in P2 skupaj tvorita izopropiliden °^H O pri čemer kondenziramo navedeni intermediat s formulo (1), kar ima za rezultat intermediat s formulo (2), kjer P1 in P2 skupaj tvorita izopropiliden, R2 predstavlja -C(=0)0R3, kjer je R3 metil in je R1 metil, SI 21463 B » · · · · · · · O. O COOMe 'Si^COOMe reagiramo navedeni ester s formulo (2) v nitrometanski derivat s formulo (3), kjer P1 in P2 skupaj tvorita izopropiliden, R2 predstavlja -C(=0)0R3, kjer je R3 metil in je R1 metil,
transformiramo navedeni intermediat s formulo (3) z uporabo baze in naknadno kisline, da dobimo intermediate s formulo (4) in (4*), kjer R2 predstavlja -C(=0)0R3, kjer je R3 metil, je R1 metil in je R4 metil, o MeOOC g/A^COOMe HQ }—COOMe
6. Postopek po kateremkoli od zahtevkov 3 do 5, kjer intermediat s formulo (3) izpostavimo Nef reakciji z uporabo kislinskega gašenja, medtem ko med navedenim gašenjem vzdržujemo temperaturo pod 10 °C.
7. Postopek po zahtevku 4 ali 5, kjer dekarboksilacijo intermediatov s formulo (4) in (4') izvedemo v zapufrani vodni raztopini.
7.1
8 N02
8. Postopek po kateremkoli od zahtevkov 3 do 5, kjer intermediat (6) pripravimo preko redukcije intermediatov s formulo (4) in (4*) ali intermediatov s formulo (5) in (5*) z uporabo litijevega borohidrida v tetrahidrofuranu ali NaBH4 v prisotnosti LiCl.
9. Postopek po kateremkoli od zahtevkov 3 do 5, kjer ciklizacijo intermediata s formulo (6) v spojino s formulo (7) izvedemo z dodajanjem močne kisline k reakcijski zmesi, ki vsebuje intermediat s formulo (6).
9- OMe O OMe dekarboksiliramo intermediate s formulo (4), kar vodi do intermediata s formulo (5), kjer je R4 metil, o Λ OMe O- reduciramo navedeni intermediat s formuo (5) z ustreznim redukcijskim sredstvom, kar ima za rezultat intermediat s formulo (6), kjer je R4 metil,
SI 21463 B
transformiramo intermediat s formulo (6) v spojino 7.1 z intramolekulamo ciklizacijsko reakcijo. HQ
10. Postopek po zahtevku 9, kjer ciklizacijsko reakcijo izvedemo pri temperaturi nižji od 5 °C.
11. Postopek po kateremkoli od zahtevkov 1 do 3, kjer intermediat s formulo (3) pripravimo s postopkom, ki obsega stopnji: prvič, kondenziranje intermediata s formulo (1) z nitrometanom, kar ima za rezultat intermediat s formulo (8) in drugič, reagiranje navedenega intermediata s formulo (8) s CHR2R8-C(=0)-0R', kjer je R8 vodik ali karboksilni ester. SI 21463 B 7
P!0
12. Postopek po zahtevku 11, kjer je karboksilni ester definiran kot C(=0)-0R1.
13. Postopek po kateremkoli od zahtevkov 1 do 5, kjer intermediat s formulo (6) pripravimo s postopkom, ki obsega stopnji: prvič, reduciranje intermediata s formulo (3), kjer je R2 vodik, z ustreznim redukcijskim sredstvom, kar ima za rezultat intermediat s formulo (9), in drugič, izpostavitev dobljenega intermediata s formulo (9) Nef reakciji z obdelavo z bazo in nato z močno kislino.
OH
14. Postopek po kateremkoli od zahtevkov 1 do 13, kjer heksahidro-furo[2,3-b]furan-3-ol s formulo (7) izoliramo z dodatkom majhnega prebitka terciarnega amina, čemur sledi odstranitev vode in odstranitev nastalih soli.
15. Postopek po kateremkoli od zahtevkov 1 do 14, kjer je vsak R1 in R3 neodvisno Ci„6alkil, aril ali arilCi_6alkil, ali skupaj z atomi, na katere sta R1 in R3 vezana, tvorita 6- do 8-člensko ciklično skupino, po izbiri substituirano s Ci.6alkilom, arilom ali arilCi^alkilom, in kjer je R4 Ci_6alkil.
16. Postopek po kateremkoli od zahtevkov 1 do 15, kjer je vsak R1, R3 in R4 neodvisno metil, etil, propil, izopropil, «-butil, izobutil, sek-butil, terc-butil ali pentil.
17. Postopek po kateremkoli od zahtevkov 1 do 16, kjer P in P skupaj tvorita kislinsko labilno vicinal-diolno zaščitno skupino. 8 SI 21463 Β
18. Postopek po kateremkoli od zahtevkov 1 do 17, kjer je P in P dialkil metilenski radikal.
19. Postopek po kateremkoli od zahtevkov 4 in 6 do 10, kjer je R5 vodik, R10-C(=0)-, (R6)3P=, kjer je R6 alkil, aril ali aralkil, ali (R70)2P(=0)-, kjer je R7 alkil, aril, aralkil.
20. Intermediat, ki ima formulo (3),
COOR kjer vsak P1 in P2 neodvisno predstavlja vodik, hidroksi-zaščitno skupino ali lahko skupaj tvorita vicinal-diolno zaščitno skupino, R1 predstavlja alkil, aril ali aralkil, R2 predstavlja vodik ali C(=0)0R3, R3 predstavlja alkil, aril ali aralkil, ali R3, če je prisoten, in R1 skupaj z atomi, na katere sta vezana, lahko tvorita 6- do 8-člensko ciklično skupino, kije lahko po izbiri substituirana z alkilom, aralkilom ali arilom; pod pogojem, da, kadar je R2 vodik in P1 in P2 skupaj tvorita izopropiliden, potem je R1 drugačen od metila ali etila.
21. Intermediat, ki ima formulo (4) ali (4'),
kjer R1 predstavlja alkil, aril ali aralkil; R2 predstavlja vodik ali C(=0)0R3; R3 predstavlja alkil, aril ali aralkil, ali R3, če je prisoten, in R1 skupaj z atomi na katere sta vezana, lahko tvorita 6- do 8-člensko ciklično skupino, ki je lahko po izbiri substituirana z alkilom, aralkilom ali arilom; OR4 predstavlja alkoholat. 9 SI 21463 Β
22. Intermediat, ki ima formulo (5) ali (5*), 9 SI 21463 Β
kjer OR4 predstavlja alkoholat.
23. Intermediat po zahtevku 22, kjer ima intermediat formulo (5a)
24. Intermediat po zahtevku 23 v kristalinični obliki.
25. Postopek za sintezo HIV proteaznega inhibitorja, kjer navedeni postopek obsega uporabo spojine s formulo (7), ki je bila pripravljena po postopku, opisanem v kateremkoli od zahtevkov 1 do 19.
26. Postopek po zahtevku 25, kjer je spojina s formulo (7) spojina s formulo (7.1). HQ
..»rt ""c 7.1
27. Postopek po zahtevku 25 ali 26, kjer je HIV proteazni inhibitor 10 SI 21463 B [(1 S,2R)-3-[[(4-aminofenil)sulfonil](2-metilpropil)amino]-2-hidroksi-1 -(fenil-metil)propil]-karbamska kislina (3R,3aS,6aR)-heksahidrofuro[2,3-b]furan-3-il ester; ali [(1 S,2R)-2-hidroksi-3-[[(4-metoksifenil)sulfonil](2-metilpropil)amino]-1 -(fenil-metil)propil]-karbamska kislina (3R,3aS,6aR)-heksahidrofuro[2,3-b]furan-3-il ester; ali [(lS,2R)-3-[(l,3-benzodioksol-5-ilsulfonil)(2-metilpropil)amino]-2-hidroksi-l-(fenilmetil)propil]-karbamska kislina (3R,3aS,6aR)-heksahidrofuro[2,3-b]furan-3-il ester; ali kakršna koli farmacevtsko sprejemljiva adicijska sol katerekoli izmed navedenih spojin.
28. Postopek po zahtevku 27, kjer je HIV proteazni inhibitor [(lS,2R)-3-[[(4-aminofenil)sulfonil](2-metilpropil)amino]-2-hidroksi-l-(fenil-metil)propil]-karbamska kislina (3R,3aS,6aR)-heksahidrofuro[2,3-b]furan-3-il ester ali kakršna koli njegova farmacevtsko sprejemljiva adicijska sol.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01203416 | 2001-09-10 | ||
| PCT/EP2002/010062 WO2003022853A1 (en) | 2001-09-10 | 2002-09-06 | Method for the preparation of hexahydro-furo[2,3-b]furan-3-ol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SI21463A SI21463A (sl) | 2004-10-31 |
| SI21463B true SI21463B (sl) | 2011-08-31 |
Family
ID=8180908
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI200220026A SI21463B (sl) | 2001-09-10 | 2002-09-06 | Postopek za pripravo heksahidro-furo/2,3-b/furan-3-ola |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US7126015B2 (sl) |
| EP (1) | EP1448567B1 (sl) |
| JP (1) | JP4521185B2 (sl) |
| KR (1) | KR100894673B1 (sl) |
| CN (2) | CN100519561C (sl) |
| AP (1) | AP1758A (sl) |
| AR (1) | AR036501A1 (sl) |
| AT (1) | ATE453648T1 (sl) |
| AU (1) | AU2002333809C1 (sl) |
| BR (1) | BRPI0212341B8 (sl) |
| CA (1) | CA2459168C (sl) |
| CY (1) | CY1109974T1 (sl) |
| DE (1) | DE60234952D1 (sl) |
| DK (1) | DK1448567T3 (sl) |
| EA (1) | EA010883B1 (sl) |
| ES (1) | ES2338538T3 (sl) |
| HK (1) | HK1068887A1 (sl) |
| HR (1) | HRP20040320B1 (sl) |
| HU (1) | HU229505B1 (sl) |
| IL (2) | IL160166A0 (sl) |
| MX (1) | MXPA04002247A (sl) |
| NO (1) | NO328934B1 (sl) |
| NZ (1) | NZ531641A (sl) |
| PL (1) | PL224030B1 (sl) |
| PT (1) | PT1448567E (sl) |
| SI (1) | SI21463B (sl) |
| WO (1) | WO2003022853A1 (sl) |
| ZA (1) | ZA200401501B (sl) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1532127E (pt) * | 2002-06-27 | 2007-01-31 | Smithkline Beecham Corp | Preparação de estereoisómeros de ( 3alfa, 3alfa/beta, 6alfa/beta )hexa-hidrofuro ( 2,3-b ) furan-3-ol |
| AU2003275675A1 (en) * | 2002-12-27 | 2004-07-29 | Sumitomo Chemical Company, Limited | Process for producing hexahydrofurofuranol derivative, intermediate thereof and process for producing the same |
| ME01059B (me) | 2003-12-23 | 2012-10-20 | Janssen Sciences Ireland Uc | Proces za pripremanje (3r,3as,6ar)-heksahidrofuro [2,3-b] furan-3-il (1s,2r)-3-[[(4-aminofenil) sulfonil] (izobutil) amino]-1-benzil-2- hidroksipropilkarbamata |
| TWI383975B (zh) * | 2004-03-31 | 2013-02-01 | Tibotec Pharm Ltd | 製備（３Ｒ，３ａＳ，６ａＲ）六氫-呋喃并〔２，３-ｂ〕呋喃-３-醇之方法 |
| JP5549898B2 (ja) * | 2006-03-31 | 2014-07-16 | 独立行政法人産業技術総合研究所 | ５−ヒドロキシメチル−２−フルフラールの製造法 |
| CN101541775B (zh) * | 2006-11-09 | 2011-12-28 | 泰博特克药品有限公司 | 六氢呋喃并[2,3-b]呋喃-3-醇的制备方法 |
| CN101024646B (zh) * | 2007-02-06 | 2010-07-14 | 启东东岳药业有限公司 | 4-甲氧基呋喃并呋喃-2-酮的纯化方法 |
| BRPI0810609A2 (pt) | 2007-04-27 | 2014-10-21 | Tibotec Pharm Ltd | Métodos para a preparação de derivados de n-isobutil-n-(2-hidróxi-a-amino-4-fenilbutil)-p-nitrobe nzenossulfonilamida |
| US8592487B2 (en) | 2007-10-26 | 2013-11-26 | Concert Pharmaceuticals, Inc. | Deuterated darunavir |
| TWI482775B (zh) | 2008-09-01 | 2015-05-01 | Tibotec Pharm Ltd | 用於製備（３ｒ，３ａｓ，６ａｒ）－六氫呋喃并〔２，３－ｂ〕呋喃－３－基（１ｓ，２ｒ）－３－〔〔（４－胺基苯基）磺醯基〕（異丁基）胺基〕－１－苯甲基－２－羥基丙基胺基甲酸酯之方法 |
| US20110257111A1 (en) * | 2008-10-24 | 2011-10-20 | Harbeson Scott L | Hydroxyethlamino Sulfonamide Derivatives |
| US8921415B2 (en) | 2009-01-29 | 2014-12-30 | Mapi Pharma Ltd. | Polymorphs of darunavir |
| BR112012009956A2 (pt) | 2009-10-30 | 2015-09-29 | Lupin Ltd | um novo processo para a preparação de darunavir e etanolato darunavir de tamanho de partícula. |
| PL2528923T3 (pl) | 2010-01-28 | 2015-01-30 | Mapi Pharma Ltd | Sposób wytwarzania darunawiru i pochodnych darunawiru |
| US8841467B2 (en) | 2010-11-23 | 2014-09-23 | Mylan Laboratories Limited | Process for the preparation of (3R, 3aS, 6aR)-hexahydrofuro [2, 3-b] furan-3-ol |
| US8802724B2 (en) | 2010-11-30 | 2014-08-12 | Purdue Research Foundation | Processes and intermediates for preparing substituted hexahydrofuro [2,3-b] furans |
| ES2848216T3 (es) | 2012-07-24 | 2021-08-05 | Laurus Labs Ltd | Un proceso para la preparación de Darunavir |
| JPWO2014024898A1 (ja) * | 2012-08-09 | 2016-07-25 | 住友化学株式会社 | ヘキサヒドロフロフラノール誘導体の製造方法 |
| CN103864813B (zh) * | 2012-12-18 | 2017-02-22 | 上海迪赛诺化学制药有限公司 | 一种合成六氢呋喃并[2,3‑b]呋喃‑3‑醇及其对映体的方法 |
| US10633390B2 (en) * | 2015-06-25 | 2020-04-28 | Msn Laboratories Private Limited | Process for the preparation of [(1S,2R)-3-[[(4-aminophenyl)sulfonyl] (2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamic acid (3R,3AS,6AR)hexahydro furo [2,3-B]furan-3-YL ester and its amorphous form |
| WO2017041228A1 (zh) * | 2015-09-08 | 2017-03-16 | 浙江九洲药业股份有限公司 | 六氢呋喃并呋喃醇衍生物的制备方法、其中间体及其制备方法 |
| CN110423228B (zh) * | 2016-02-05 | 2023-01-10 | 成都博腾药业有限公司 | 一种制备地瑞那韦中间体的方法 |
| EP3532478B1 (en) | 2016-10-27 | 2021-05-26 | Gilead Sciences, Inc. | Crystalline form of darunavir free base |
| CN106928248B (zh) * | 2017-02-04 | 2019-01-04 | 青岛科技大学 | 一种制备(3R,3aS,6aR)六氢呋喃并[2,3-b]呋喃-3-醇的方法 |
| CN110272398B (zh) | 2018-03-16 | 2022-11-29 | 江苏瑞科医药科技有限公司 | 六氢呋喃并呋喃醇衍生物的制备方法、其中间体及其制备方法 |
| CN114853774A (zh) * | 2022-06-24 | 2022-08-05 | 盐城迪赛诺制药有限公司 | 一种达卢那韦关键中间体的制备方法 |
| CN115557964A (zh) * | 2022-10-18 | 2023-01-03 | 启东东岳药业有限公司 | 一种药物化合物的制备方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4325970A (en) * | 1980-10-09 | 1982-04-20 | Hoffmann-La Roche Inc. | 15-Acetyl-prostaglandins |
| NZ224497A (en) * | 1987-05-18 | 1990-04-26 | Janssen Pharmaceutica Nv | Pharmaceutical composition comprising flunarizine |
| US5281420A (en) * | 1992-05-19 | 1994-01-25 | The Procter & Gamble Company | Solid dispersion compositions of tebufelone |
| AU6828894A (en) * | 1993-05-14 | 1994-12-12 | Merck & Co., Inc. | Hiv protease inhibitors |
| DE69415326T2 (de) | 1993-08-24 | 1999-06-02 | Searle & Co | Hydroxyaminosulfonamide verwendbar als inhibitoren retroviraler proteasen |
| RU2089545C1 (ru) * | 1994-09-28 | 1997-09-10 | Ярославский государственный технический университет | Способ получения 2-метил-2-этил-1,3-диоксолан-4-ил-метилметакрилата |
| DE19510566A1 (de) * | 1995-03-23 | 1996-09-26 | Kali Chemie Pharma Gmbh | Benzazepin-, Benzoxazepin- und Benzothiazepin-N-essigsäurederivate sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
| DE19638020A1 (de) * | 1996-09-18 | 1998-03-19 | Solvay Pharm Gmbh | Die gastrointestinale Durchblutung fördernde Arzneimittel |
| RU2211047C2 (ru) * | 1997-01-30 | 2003-08-27 | Новартис Аг | Желатиновые капсулы с твердым покрытием, включающие фармацевтические композиции, практически не содержащие масел |
| WO1999067254A2 (en) * | 1998-06-23 | 1999-12-29 | The United States Of America Represented By The Secretary, Department Of Health And Human Services | Multi-drug resistant retroviral protease inhibitors and use thereof |
| CA2872424C (en) | 1998-06-23 | 2017-03-07 | The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Bisfuran derivatives useful in preventing the emergence of multidrug resistant hiv strains and treatment of hiv |
| KR100336090B1 (ko) * | 1998-06-27 | 2002-05-27 | 윤승원 | 오일, 지방산 또는 이들의 혼합물을 함유한 난용성 약물의 고형분산제제 |
| DE19906310A1 (de) * | 1999-02-16 | 2000-08-17 | Solvay Pharm Gmbh | Arzneimittel zur Behandlung von Bluthochdruck |
| DE19932555A1 (de) * | 1999-07-13 | 2001-01-18 | Solvay Pharm Gmbh | Arzneimittel mit protektiver Wirkung gegen oxidativ-toxische und insbesondere gegen kardiotoxische Substanzen |
| HU228938B1 (hu) * | 1999-10-06 | 2013-06-28 | Us Government | Hexahidrofuro[2,3-b]furán-3-il-N-{3-(1,3-benzodioxol-5-il-szulfonil)-(izobutil)-amino-1-benzil-2- -(hidroxi-propil)}-karbamát mint retrovírus proteáz gátló |
-
2002
- 2002-09-06 BR BRPI0212341A patent/BRPI0212341B8/pt not_active IP Right Cessation
- 2002-09-06 EP EP02797968A patent/EP1448567B1/en not_active Expired - Lifetime
- 2002-09-06 ES ES02797968T patent/ES2338538T3/es not_active Expired - Lifetime
- 2002-09-06 JP JP2003526927A patent/JP4521185B2/ja not_active Expired - Lifetime
- 2002-09-06 PT PT02797968T patent/PT1448567E/pt unknown
- 2002-09-06 CN CNB028176391A patent/CN100519561C/zh not_active Expired - Lifetime
- 2002-09-06 CN CN200710186668XA patent/CN101172980B/zh not_active Expired - Lifetime
- 2002-09-06 AT AT02797968T patent/ATE453648T1/de active
- 2002-09-06 EA EA200400430A patent/EA010883B1/ru not_active IP Right Cessation
- 2002-09-06 DK DK02797968.1T patent/DK1448567T3/da active
- 2002-09-06 IL IL16016602A patent/IL160166A0/xx unknown
- 2002-09-06 US US10/489,059 patent/US7126015B2/en not_active Expired - Lifetime
- 2002-09-06 SI SI200220026A patent/SI21463B/sl active Search and Examination
- 2002-09-06 KR KR1020047002113A patent/KR100894673B1/ko active IP Right Grant
- 2002-09-06 DE DE60234952T patent/DE60234952D1/de not_active Expired - Lifetime
- 2002-09-06 PL PL367817A patent/PL224030B1/pl unknown
- 2002-09-06 AU AU2002333809A patent/AU2002333809C1/en not_active Expired
- 2002-09-06 AP APAP/P/2004/002981A patent/AP1758A/en active
- 2002-09-06 WO PCT/EP2002/010062 patent/WO2003022853A1/en active IP Right Grant
- 2002-09-06 HU HU0402140A patent/HU229505B1/hu unknown
- 2002-09-06 MX MXPA04002247A patent/MXPA04002247A/es active IP Right Grant
- 2002-09-06 NZ NZ531641A patent/NZ531641A/en not_active IP Right Cessation
- 2002-09-06 CA CA2459168A patent/CA2459168C/en not_active Expired - Lifetime
- 2002-09-09 AR ARP020103403A patent/AR036501A1/es active IP Right Grant
-
2004
- 2004-02-02 IL IL160166A patent/IL160166A/en active IP Right Grant
- 2004-02-24 ZA ZA2004/01501A patent/ZA200401501B/en unknown
- 2004-04-05 HR HRP20040320AA patent/HRP20040320B1/hr not_active IP Right Cessation
- 2004-04-06 NO NO20041434A patent/NO328934B1/no not_active IP Right Cessation
-
2005
- 2005-02-23 HK HK05101515.9A patent/HK1068887A1/xx not_active IP Right Cessation
-
2010
- 2010-03-30 CY CY20101100296T patent/CY1109974T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SI21463B (sl) | Postopek za pripravo heksahidro-furo/2,3-b/furan-3-ola | |
| HRP20161031T1 (hr) | POSTUPCI ZA PRIPREMANJE (3R,3aS,6aR) HEKSAHIDRO-FURO[2,3-b]FURAN-3-OLA | |
| NZ598172A (en) | Synthesis of boronic ester and acid compounds | |
| HUP0002953A2 (hu) | Eljárás citalopram előállítására és a használt köztitermékek | |
| MXPA02008228A (es) | Metodo para la preparacion de citalopram. | |
| RS51210B (sr) | Dobijanje pregaballina i srodnih jedinjenja | |
| ATE441627T1 (de) | Verfahren zur herstellung von valsartan | |
| DE60117963D1 (de) | Verfahren zu herstellung von citalopram | |
| Looper et al. | Syntheses of the cylindrospermopsin alkaloids | |
| CN102712572A (zh) | 一种用于获得 3，3-二苯基丙胺的方法 | |
| KR20070110941A (ko) | 타달라필 중간체의 제조 방법 | |
| RU2013137751A (ru) | Способ получения гиразы и ингибиторов топоизомеразы | |
| EA200200939A1 (ru) | Способ получения циталопрама | |
| DK1194397T3 (da) | Fremgangsmåde til fremstilling af (nitroxymethyl)phenylestere af salicylderivater | |
| EA200100969A1 (ru) | Новые соединения циклобутендиона, способ их получения и содержащие их фармацевтические композиции | |
| HRP20040198B1 (en) | Process for the production of beraprost and its salts | |
| EE05064B1 (et) | Meetod tuntud tetrasooli derivaadi snteesiks | |
| EP1160236A3 (en) | Production of mixed acid anhydride and amine compound | |
| BR0109268A (pt) | Método de preparação de citalopram, composto e citaplopram | |
| RU2003110580A (ru) | Способ очистки правастатина | |
| AR029893A1 (es) | Metodo para la preparacion de citalopram, intermediarios y composicion farmaceutica | |
| Goswami et al. | Dinitroaliphatics as linkers: application in the synthesis of novel artemisinin carba-dimer | |
| Nifontov et al. | Spirocyclohexadienones. 7. Three-component condensation of 1-or 2-methoxynaphthalene with isobutyraldehyde and nitriles | |
| IS6636A (is) | Hringlaga ketonar og notkun þeirra í smíði amínósýra | |
| Lüsch et al. | New access to the synthetic building block l-aspartic acid β-semialdehyde via Grignard reaction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OO00 | Grant of patent |
Effective date: 20040823 |
|
| IF | Valid on the event date | ||
| SP73 | Change of data on owner |
Owner name: TIBOTEC PHARMACEUTICALS LTD.; IE Effective date: 20070126 |
|
| OU02 | Decision according to article 73(2) ipa 1992, publication of decision on partial fulfilment of the invention and change of patent claims |
Effective date: 20110706 |
|
| SP73 | Change of data on owner |
Owner name: JANSSEN SCIENCES IRELAND UC; IE Effective date: 20151216 |