WO2001010851B1 - Process for the preparation of lysine-carboxyanhydride intermediates in the synthesis of lisinopril - Google Patents
Process for the preparation of lysine-carboxyanhydride intermediates in the synthesis of lisinoprilInfo
- Publication number
- WO2001010851B1 WO2001010851B1 PCT/EP2000/007743 EP0007743W WO0110851B1 WO 2001010851 B1 WO2001010851 B1 WO 2001010851B1 EP 0007743 W EP0007743 W EP 0007743W WO 0110851 B1 WO0110851 B1 WO 0110851B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- group
- formula
- reaction
- reacting
- Prior art date
Links
- 108010007859 Lisinopril Proteins 0.000 title claims abstract 3
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 title claims abstract 3
- 229960002394 lisinopril Drugs 0.000 title claims abstract 3
- 238000000034 method Methods 0.000 title claims 8
- 230000015572 biosynthetic process Effects 0.000 title 1
- 239000000543 intermediate Substances 0.000 title 1
- 238000002360 preparation method Methods 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- 239000003795 chemical substances by application Substances 0.000 claims abstract 6
- 150000001875 compounds Chemical class 0.000 claims abstract 6
- 230000002140 halogenating effect Effects 0.000 claims abstract 6
- 239000002253 acid Substances 0.000 claims abstract 5
- 238000006243 chemical reaction Methods 0.000 claims abstract 5
- 238000004519 manufacturing process Methods 0.000 claims abstract 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract 3
- 150000001768 cations Chemical group 0.000 claims abstract 3
- 150000003839 salts Chemical class 0.000 claims abstract 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract 2
- 150000004820 halides Chemical class 0.000 claims abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 2
- 239000001257 hydrogen Substances 0.000 claims abstract 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract 2
- 125000006239 protecting group Chemical group 0.000 claims abstract 2
- 238000007363 ring formation reaction Methods 0.000 claims abstract 2
- 229920006395 saturated elastomer Polymers 0.000 claims abstract 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims 4
- 239000002609 medium Substances 0.000 claims 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- NIRCAUPPZAUKDX-UHFFFAOYSA-N 5-benzyl-2-[[4-(3-chlorophenyl)piperazin-1-yl]methyl]-6-methylpyridazin-3-one Chemical compound O=C1C=C(CC=2C=CC=CC=2)C(C)=NN1CN(CC1)CCN1C1=CC=CC(Cl)=C1 NIRCAUPPZAUKDX-UHFFFAOYSA-N 0.000 claims 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 1
- 239000004472 Lysine Substances 0.000 claims 1
- 229910019213 POCl3 Inorganic materials 0.000 claims 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims 1
- 239000012736 aqueous medium Substances 0.000 claims 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- HKYGSMOFSFOEIP-UHFFFAOYSA-N dichloro(dichloromethoxy)methane Chemical compound ClC(Cl)OC(Cl)Cl HKYGSMOFSFOEIP-UHFFFAOYSA-N 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 claims 1
- 150000008282 halocarbons Chemical class 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 125000006000 trichloroethyl group Chemical group 0.000 claims 1
- RTPWGXQKCQKLGK-UHFFFAOYSA-N CC(C(OC=O)=O)NC Chemical compound CC(C(OC=O)=O)NC RTPWGXQKCQKLGK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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
- C07D263/44—Two oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- C07K5/06086—Dipeptides with the first amino acid being basic
-
- 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)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Control Of Vending Devices And Auxiliary Devices For Vending Devices (AREA)
- Farming Of Fish And Shellfish (AREA)
- Table Devices Or Equipment (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Process for preparing a compound of formula (III), wherein R is a linear or branched, saturated or unsaturated, substituted or unsubstituted alkyl-, aryl-, or aralkyl group having 1 to 30 carbon atoms, comprising a reaction (b) of a compound of formula (II), wherein R is as defined above and X is hydrogen or a cation of a corresponding acid salt, R' is COOR, COR or any other protecting group for amino functions, wherein R is again as defined above, with at least one halogenating agent yielding an acid halide by reacting at the COOX-group of the compound of formula (II) and being respectively capable of causing ring formation, under the proviso that thionyl chloride is excluded from the halogenating agents to be used and process for preparing lisinopril comprising the above reaction.
Claims
1 7
AMENDED CLAIMS
[received by the International Bureau on 8 February 2001 (08.02.01); original claim 4 cancelled; original claim 1 amended; remaining claims unchanged
(3 pages)]
L A process for preparing lisinopril or a derivative thereof comprising a process for preparing a compound of formula III
wherein R is a linear or branched, saturated or unsaturated, substituted or unsubstituted alkyl-, aryl,- or aralkyl group having 1 to 30 carbon atoms,
comprising a reaction (b) of a compound of formula II
RO— ? C— NH— CH— (CH2)4-NH-R' II
COOX
wherein R is as defined above and X is hydrogen or a cation of a corresponding acid salt, R' is COOR, COR or any other protecting group for amino functions, wherein R is again as defined above, 1 8
with at least one halogenating agent yielding an acid halide by reacting at the COOX-group of the compound of the formula II and being respectively capable of causing ring formation,
under the proviso that thionyl chloride is excluded from the halogenating agents to be used.
2. A process as claimed in claim 1, comprising a reaction (a) of reacting lysine or a derivative thereof with a haloformate of the general formula I
RO— ? C— Hal
wherein R is defined as in claim 1 and the Hal represents a halogen atom, preferably CI and Br
in the presence of an alkaline aqueous medium, which may comprise one or more organic sovents, preferably water-miscible solvents to obtain compound
II.
3. A process as claimed in claim 1 or 2, further comprising a reaction (c) of reacting the compound of formula III with proline or a derivative thereof in an alkaline medium to obtain a compound IV
COOR" wherein R is as defined in claim 1 and R" is H, a cation of an acid salt or a group R.
4. Process as claimed in any of the claims 1 to 3, wherein R is selected from the group consisting of allyl, benzyl, ethyl, isopropyl, isobutyl, tert.-butyl and tri- chloro ethyl.
5. Process as claimed in any of the claims 1 to 4, wherein the halogenating agents are respectively selected from the group consisting of oxalyl chloride, cyanuric chloride, PC13, POCl3, PC15 and dichloromethyl ether.
6. Process as claimed in claim 5, wherein the halogenating agent is oxalyl chloride, preferably being used together with DMF.
7. Process as claimed in any of the claims 1 to 6, wherein step (a) is carried out at a pH value between 10 and 12 at a temperature between 10°C and 30°C for a period of time between two and six hours, step (b) is carried out in a solvent selected from ketones, cyclic and linear ethers, esters, halogenated hydrocar- bons and aromatic hydrocarbons at a temperature between 0°C and +30°C for a period of time between two and six hours, and step (c) is carried out at a temperature between -10°C and +10°C for a period of time between 1 and 3 hours in a hydroacetonic alkaline medium.
8. A process as described in the above-mentioned claims and specified by the scope of protection of said claims.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU72742/00A AU7274200A (en) | 1999-08-09 | 2000-08-09 | Process for the preparation of lysine-carboxyanhydride intermediates in the synthesis of lisinopril |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT1999TO000703A IT1307265B1 (en) | 1999-08-09 | 1999-08-09 | PROCEDURE FOR THE PREPARATION OF INTERMEDIATE PRODUCTS IN THE SYNTHESID OF LISINOPRIL. |
| ITTO99A000703 | 1999-08-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2001010851A1 WO2001010851A1 (en) | 2001-02-15 |
| WO2001010851B1 true WO2001010851B1 (en) | 2001-06-21 |
Family
ID=11418023
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2000/007743 WO2001010851A1 (en) | 1999-08-09 | 2000-08-09 | Process for the preparation of lysine-carboxyanhydride intermediates in the synthesis of lisinopril |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU7274200A (en) |
| IT (1) | IT1307265B1 (en) |
| WO (1) | WO2001010851A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR0102252B1 (en) | 2001-04-10 | 2013-10-22 | Angiotensin II AT1 Receptor Antagonist Controlled Release System, Pharmaceutical Composition and Use | |
| US20070093664A1 (en) * | 2002-06-19 | 2007-04-26 | Tuncer Aslan | Process for the production of lisinopril |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5019521A (en) * | 1990-03-12 | 1991-05-28 | Photest Diagnostics, Inc. | Paired polypeptides |
| IT1299341B1 (en) * | 1998-02-09 | 2000-03-16 | Pfc Italiana Srl | PROCESS FOR THE PRODUCTION OF INTERMEDIATE ALKOXY CARBONYL DIPEPTIDES IN THE SYNTHESIS OF LISINOPRIL. |
-
1999
- 1999-08-09 IT IT1999TO000703A patent/IT1307265B1/en active
-
2000
- 2000-08-09 WO PCT/EP2000/007743 patent/WO2001010851A1/en active Application Filing
- 2000-08-09 AU AU72742/00A patent/AU7274200A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU7274200A (en) | 2001-03-05 |
| IT1307265B1 (en) | 2001-10-30 |
| WO2001010851A1 (en) | 2001-02-15 |
| ITTO990703A1 (en) | 2001-02-09 |
| ITTO990703A0 (en) | 1999-08-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0283970A3 (en) | New peptide compounds, a process for the preparation thereof and pharmaceutical composition comprising the same | |
| CA2166902A1 (en) | 3-amidopyrazole derivatives, process for preparing these and pharmaceutical compositions containing them | |
| CA2533685A1 (en) | Nitrogen-containing fused heterocyclic carboxylic acid compounds | |
| FI970427A0 (en) | Method for preparing antimicrobial compounds | |
| KR890014486A (en) | Use of N-cyclopropylaniline in the preparation of N-cyclopropylaniyl and 1-cyclopropyl-quinolonecarboxylic acid and derivatives thereof | |
| KR960014271A (en) | Method for producing a diaryl diketopyrrolopyrrole pigment | |
| WO2001010851B1 (en) | Process for the preparation of lysine-carboxyanhydride intermediates in the synthesis of lisinopril | |
| ES2167869T3 (en) | PROCEDURE TO PREPARE NICOTINIC ACIDS. | |
| EP0234514A3 (en) | Pyrazolopyrimidines, intermediates thereof and processes for the preparation of them | |
| AU539870B2 (en) | 2-phenylamino-imidazolines-(2) | |
| NO972461L (en) | Preparation of cefem and isooxacefem derivatives | |
| DE69427541T2 (en) | Process for the preparation of sulfonylurea derivatives | |
| GB1505020A (en) | Substituted 2-phenylimino-thiazolines a process for their preparation and their use as ectoparasiticides | |
| IL56507A (en) | (trihalomethyl)dimethyloxabicyclohexanone derivatives for the preparation of cis dihalovinyldimethylcyclopropanecarboxylic acids | |
| CA2182241A1 (en) | Methods for the manufacture of nefazodone | |
| JP2005520805A5 (en) | ||
| DE60000375D1 (en) | Process for the preparation of difluoroacetophenone derivatives | |
| ES448741A1 (en) | Procedure for the preparation of 6-aminopenicilanico or 7-aminodexacetoxicefalosporanico ácidos derivados. (Machine-translation by Google Translate, not legally binding) | |
| GB1527047A (en) | 3-amino-4-carboalkoxy-benzoic acid 4'-phenoxyanilides process for their preparation and their use | |
| CA2337248A1 (en) | Process for the preparation of an indole derivative | |
| DK248287A (en) | PROCEDURE FOR THE PREPARATION OF CHEPHALOSPORINE DERIVATIVES | |
| CA2113349A1 (en) | Method of producing a quinolonecarboxylic acid derivative | |
| DK566181A (en) | PROCEDURE FOR THE PREPARATION OF N-PYRROLYLPYRIDAZINE AMINE DERIVATIVES | |
| AU525425B2 (en) | Alpha,beta-dihaloalkyl isocyanates | |
| SE8207477L (en) | PROCEDURE FOR PREPARING HETEROCYCLIC ETHIC ACID DERIVATIVES |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| AK | Designated states |
Kind code of ref document: B1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
| AL | Designated countries for regional patents |
Kind code of ref document: B1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
| B | Later publication of amended claims | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 2000960424 Country of ref document: EP |
|
| REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
| WWW | Wipo information: withdrawn in national office |
Ref document number: 2000960424 Country of ref document: EP |
|
| NENP | Non-entry into the national phase |
Ref country code: JP |
|
| 122 | Ep: pct application non-entry in european phase |