HUP0202437A2 - Új eljárás (2S,3aS,7aS)-1-[(S)-alanil]oktahidro-1H-indol-2-karbonsav vegyületek előállítására és ezek alkalmazása perindopril előállítására - Google Patents
Új eljárás (2S,3aS,7aS)-1-[(S)-alanil]oktahidro-1H-indol-2-karbonsav vegyületek előállítására és ezek alkalmazása perindopril előállításáraInfo
- Publication number
- HUP0202437A2 HUP0202437A2 HU0202437A HUP0202437A HUP0202437A2 HU P0202437 A2 HUP0202437 A2 HU P0202437A2 HU 0202437 A HU0202437 A HU 0202437A HU P0202437 A HUP0202437 A HU P0202437A HU P0202437 A2 HUP0202437 A2 HU P0202437A2
- Authority
- HU
- Hungary
- Prior art keywords
- general formula
- compound
- moles
- perindopril
- mole
- Prior art date
Links
- 238000000034 method Methods 0.000 title abstract 4
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 title abstract 2
- 229960002582 perindopril Drugs 0.000 title abstract 2
- 239000002253 acid Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 abstract 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 abstract 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 abstract 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 abstract 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 abstract 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 229910019020 PtO2 Inorganic materials 0.000 abstract 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 abstract 1
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical group O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 abstract 1
- 235000004279 alanine Nutrition 0.000 abstract 1
- -1 alanine compound Chemical class 0.000 abstract 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 229910052799 carbon Chemical group 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 abstract 1
- 150000002148 esters Chemical class 0.000 abstract 1
- 125000000524 functional group Chemical group 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 238000002955 isolation Methods 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 229910052759 nickel Inorganic materials 0.000 abstract 1
- 239000003960 organic solvent Substances 0.000 abstract 1
- 229910052763 palladium Inorganic materials 0.000 abstract 1
- 229910052697 platinum Inorganic materials 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 238000001953 recrystallisation Methods 0.000 abstract 1
- 229910052707 ruthenium Inorganic materials 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
-
- 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)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Indole Compounds (AREA)
Abstract
A találmány tárgya az (I) általános képletű vegyületek ipari szintéziseljárása, ahol a képletben R1 jelentése hidrogénatom, lineáris vagyelágazó szénláncú 1-6 szénatomos alkilcsoport vagy benzilcsoport, ésR2 jelentése egy amino funkciós csoportot védő csoport. Az eljárássorán egy (V) általános képletű észtert, ahol R1 jelentése az (I)általános képletnél megadott, reagáltatnak egy (VI) általános képletűalanin vegyülettel, ahol R2 jelentése az (I) általános képletnélmegadott, egy szerves oldószerben, 1-hidroxibenzotriazol távollétébenvagy az alkalmazott (V) általános képletű vegyületek 1 móljáravonatkoztatva 0,6 mólnál kevesebb mennyiségű 1-hidroxibenzotriazoljelenlétében, az alkalmazott (V) általános képletű vegyület 1 móljáravonatkoztatva 1-1,2 mól diciklohexilkarbodiimid jelenlétében és azalkalmazott (V) általános képletű vegyület 1 móljára vonatkoztatva 1-1,2 mól trietilamin jelenlétében 20-50 °C hőmérsékleten, és ily módonizolálás, majd átkristályosítás után (VII) általános képletűvegyületet kapnak, ahol R1 és R2 jelentése a fentiekben megadott, amitazután egy katalizátor jelenlétében, előnyösen PtO2 vagy szénhordozóspalládium, ruténium, platina vagy nikkel jelenlétében 1-40 barhidrogénnyomáson 30-70 °C hőmérsékleten. A találmány tárgya továbbá atalálmány szerinti eljárással előállított vegyületek alkalmazásaperindopril és ennek gyógyászatilag elfogadható sói előállítására. Ó
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0109839A FR2827860B1 (fr) | 2001-07-24 | 2001-07-24 | Nouveau procede de synthese de derives de l'acide (2s, 3as, 7as)-1-[(s)-alanyl]-octahydro-1h-indole-2-carboxyline et application a la synthese du perindopril |
Publications (4)
Publication Number | Publication Date |
---|---|
HU0202437D0 HU0202437D0 (hu) | 2002-10-28 |
HUP0202437A2 true HUP0202437A2 (hu) | 2003-02-28 |
HUP0202437A3 HUP0202437A3 (en) | 2003-05-28 |
HU229396B1 HU229396B1 (hu) | 2013-11-28 |
Family
ID=8865826
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HU0202437A HU229396B1 (hu) | 2001-07-24 | 2002-07-24 | Új eljárás (2S,3aS,7aS)-1-[(S)-alanil]oktahidro-1H-indol-2-karbonsav vegyületek elõállítására és ezek alkalmazása perindopril elõállítására |
Country Status (25)
Country | Link |
---|---|
US (1) | US7060842B2 (hu) |
EP (1) | EP1256590B1 (hu) |
JP (1) | JP3868957B2 (hu) |
KR (1) | KR100607556B1 (hu) |
CN (1) | CN1533398A (hu) |
AR (1) | AR035081A1 (hu) |
AT (1) | ATE318838T1 (hu) |
AU (1) | AU2002334027B8 (hu) |
BR (1) | BR0211334A (hu) |
CA (1) | CA2455706C (hu) |
DE (1) | DE60209458T2 (hu) |
DK (1) | DK1256590T3 (hu) |
EA (1) | EA005490B1 (hu) |
ES (1) | ES2259071T3 (hu) |
FR (1) | FR2827860B1 (hu) |
HU (1) | HU229396B1 (hu) |
MA (1) | MA27130A1 (hu) |
MX (1) | MXPA04000443A (hu) |
NO (1) | NO328234B1 (hu) |
NZ (1) | NZ530427A (hu) |
PL (1) | PL212408B1 (hu) |
PT (1) | PT1256590E (hu) |
SI (1) | SI1256590T1 (hu) |
WO (1) | WO2003016336A1 (hu) |
ZA (1) | ZA200400246B (hu) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE60220877T2 (de) * | 2002-01-30 | 2008-04-10 | Les Laboratoires Servier | Verfahren zur Herstellung von hochreinem Perindopril und Zwischenverbindungen nützlich in der Synthese |
EP1403275B1 (fr) * | 2003-02-28 | 2005-10-19 | Les Laboratoires Servier | Nouveau procédé de synthèse du perindopril et de ses sels pharmaceutiquement acceptables |
ATE395913T1 (de) | 2003-02-28 | 2008-06-15 | Servier S A Lab | Verfahren zur herstellung von perindopril |
ES2249691T3 (es) * | 2003-02-28 | 2006-04-01 | Les Laboratoires Servier | Procedimiento de sintesis de derivados del acido (2s,3as,7as)-1-(s)-alanil)-octahidro-1h-indol-2-carboxilico y su utilizacion en la sintesis de perindopril. |
DE60301980T2 (de) * | 2003-02-28 | 2006-07-27 | Les Laboratoires Servier | Verfahren zur Synthese des (2S,3aS,7aS)-perhydroindol-2-carbonsäures und seiner Estern, Verwendung in der Synthese von Perindopril |
DE60300106T2 (de) * | 2003-03-12 | 2005-10-13 | Les Laboratoires Servier | Verfahren zur Synthese von (2S,3aS,7aS)-1-((S)-Alanyl)-octahydro-1H-indol-2-carbonsäurederivaten und Verwendung in der Synthese von Perindopril |
EP1321471B1 (fr) * | 2003-03-12 | 2005-05-04 | Les Laboratoires Servier | Nouveau procédé de synthèse du perindopril et de ses sels pharmaceutiquement acceptables |
PT1323729E (pt) * | 2003-03-12 | 2005-02-28 | Servier Lab | Novo processo de sintese do acido (2s,3as, 7as)-per-hidroindole-2-carboxilico e os seus esteres e aplicacao a sintese do perindopril |
PL1636185T3 (pl) | 2003-06-24 | 2012-12-31 | Servier Lab | Nowe formy krystaliczne peryndoprylu erbuminy |
ATE337332T1 (de) * | 2003-07-31 | 2006-09-15 | Servier Lab | Verfahren für die synthese von perindopril und seiner pharmazeutischen annehmbaren salzen |
JP4720132B2 (ja) * | 2003-10-30 | 2011-07-13 | 住友化学株式会社 | 光学活性なn−保護−オクタヒドロ−1h−インドール−2−カルボン酸の製造方法 |
EP1420030A3 (fr) * | 2003-12-10 | 2004-05-26 | Les Laboratoires Servier | Procédé de synthèse de dérivés de l'acide (2S, 3aS, 7aS) - 1 - [(S)-alanyl]-octahydro-1H-indole-2-carboxylique et application à la synthèse du perindopril |
GB2413128A (en) | 2004-04-13 | 2005-10-19 | Neopharma Ltd | Process for the preparation of perindopril |
ITFI20040174A1 (it) * | 2004-08-03 | 2004-11-03 | Protera S R L | Derivati arilsolfonammidici dell'acido idrossammico ad azione inibitoria di metalloproteinasi |
KR101329457B1 (ko) | 2006-12-19 | 2013-11-15 | 에스케이바이오팜 주식회사 | 옥타하이드로인돌-2-카르복시산의 제조방법 |
FR3050380B1 (fr) | 2016-04-20 | 2020-07-10 | Les Laboratoires Servier | Composition pharmaceutique comprenant un betabloquant, un inhibiteur de l'enzyme de conversion et un antihypertenseur ou un ains. |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2503155A2 (fr) * | 1980-10-02 | 1982-10-08 | Science Union & Cie | Nouveaux imino diacides substitues, leurs procedes de preparation et leur emploi comme inhibiteur d'enzyme |
FR2620709B1 (fr) * | 1987-09-17 | 1990-09-07 | Adir | Procede de synthese industrielle du perindopril et de ses principaux intermediaires de synthese |
FR2807037B1 (fr) * | 2000-03-31 | 2002-05-10 | Adir | NOUVEAU PROCEDE DE SYNTHESE DES ESTERS DE LA N-[(s)-1- CARBOXYBUTYL]-(S)-ALANINE ET APPLICATION A LA SYNTHESE DU PERINDOPRIL |
FR2807431B1 (fr) | 2000-04-06 | 2002-07-19 | Adir | Nouveau procede de synthese du perindopril et de ses sels pharmaceutiquement acceptables |
FR2807430B1 (fr) | 2000-04-11 | 2002-05-17 | Adir | Nouveau procede de synthese des esters de la n-[(s)-1- carboxybutyl]-(s)-alanine et application a la synthese du perindopril |
-
2001
- 2001-07-24 FR FR0109839A patent/FR2827860B1/fr not_active Expired - Fee Related
-
2002
- 2002-07-23 JP JP2003521258A patent/JP3868957B2/ja not_active Expired - Fee Related
- 2002-07-23 AR ARP020102757A patent/AR035081A1/es not_active Application Discontinuation
- 2002-07-23 ES ES02291853T patent/ES2259071T3/es not_active Expired - Lifetime
- 2002-07-23 EA EA200400110A patent/EA005490B1/ru not_active IP Right Cessation
- 2002-07-23 AT AT02291853T patent/ATE318838T1/de active
- 2002-07-23 DE DE60209458T patent/DE60209458T2/de not_active Expired - Lifetime
- 2002-07-23 EP EP02291853A patent/EP1256590B1/fr not_active Expired - Lifetime
- 2002-07-23 US US10/484,022 patent/US7060842B2/en not_active Expired - Lifetime
- 2002-07-23 DK DK02291853T patent/DK1256590T3/da active
- 2002-07-23 KR KR1020047001052A patent/KR100607556B1/ko not_active IP Right Cessation
- 2002-07-23 SI SI200230292T patent/SI1256590T1/sl unknown
- 2002-07-23 AU AU2002334027A patent/AU2002334027B8/en not_active Ceased
- 2002-07-23 CN CNA028146093A patent/CN1533398A/zh active Pending
- 2002-07-23 BR BR0211334-1A patent/BR0211334A/pt not_active IP Right Cessation
- 2002-07-23 CA CA2455706A patent/CA2455706C/fr not_active Expired - Fee Related
- 2002-07-23 PT PT02291853T patent/PT1256590E/pt unknown
- 2002-07-23 MX MXPA04000443A patent/MXPA04000443A/es active IP Right Grant
- 2002-07-23 WO PCT/FR2002/002627 patent/WO2003016336A1/fr active IP Right Grant
- 2002-07-23 NZ NZ530427A patent/NZ530427A/en not_active IP Right Cessation
- 2002-07-24 PL PL355159A patent/PL212408B1/pl unknown
- 2002-07-24 HU HU0202437A patent/HU229396B1/hu not_active IP Right Cessation
-
2004
- 2004-01-08 MA MA27474A patent/MA27130A1/fr unknown
- 2004-01-13 ZA ZA200400246A patent/ZA200400246B/en unknown
- 2004-01-13 NO NO20040151A patent/NO328234B1/no not_active IP Right Cessation
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