DE3038950A1 - METHOD FOR PRODUCING (2S) -6- ((AMINOPHENYLACETYL) -AMINO) -3,3-DIMETHYL-7-OXO-4-THIA-1-AZABICYCLOL (3.2.0) HEPTAN-2-CARBONIC ACID-1,3- DIHYDRO-3-OXO-1-ISOBENZOFURANYLESTER - Google Patents
METHOD FOR PRODUCING (2S) -6- ((AMINOPHENYLACETYL) -AMINO) -3,3-DIMETHYL-7-OXO-4-THIA-1-AZABICYCLOL (3.2.0) HEPTAN-2-CARBONIC ACID-1,3- DIHYDRO-3-OXO-1-ISOBENZOFURANYLESTERInfo
- Publication number
- DE3038950A1 DE3038950A1 DE19803038950 DE3038950A DE3038950A1 DE 3038950 A1 DE3038950 A1 DE 3038950A1 DE 19803038950 DE19803038950 DE 19803038950 DE 3038950 A DE3038950 A DE 3038950A DE 3038950 A1 DE3038950 A1 DE 3038950A1
- Authority
- DE
- Germany
- Prior art keywords
- oxo
- dihydro
- aminophenylacetyl
- thia
- dimethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- -1 (AMINOPHENYLACETYL) -AMINO Chemical class 0.000 title claims description 11
- 238000004519 manufacturing process Methods 0.000 title 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- LJGFJCOLMZZTBJ-UHFFFAOYSA-N 4-phenyl-1,3-thiazolidine-2,5-dione Chemical compound O=C1SC(=O)NC1C1=CC=CC=C1 LJGFJCOLMZZTBJ-UHFFFAOYSA-N 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- YAUCGRHYMHRNPV-UHFFFAOYSA-N 2,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound OC(=O)C1(C)C(C)SC2CC(=O)N21 YAUCGRHYMHRNPV-UHFFFAOYSA-N 0.000 claims 1
- 238000006482 condensation reaction Methods 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 claims 1
- 239000012429 reaction media Substances 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 229960002780 talampicillin Drugs 0.000 description 6
- SOROUYSPFADXSN-SUWVAFIASA-N talampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(=O)OC2C3=CC=CC=C3C(=O)O2)(C)C)=CC=CC=C1 SOROUYSPFADXSN-SUWVAFIASA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003021 water soluble solvent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Μϋΐ.Ι,ΕΡ-ΗΟΗΚ · «>K!JFKI. · SCHÖN · HHIiTELΜϋΐ.Ι, ΕΡ-ΗΟΗΚ · «> K! JFKI. · SCHÖN · HHITEL
-3--3-
DR. WOLFGANG MULLER-BORE (PATENTANWALTVON 1927-1975) DR. PAUL DEUFEL. DIPL.-CHEM. DR. ALFRED SCHÖN. DIPLi-CHEM. WERNER HERTEL, D1PL.-PHYS.DR. WOLFGANG MULLER-BORE (PATENT ADVERTISER FROM 1927-1975) DR. PAUL DEUFEL. DIPL.-CHEM. DR. ALFRED SCHÖN. DIPLi-CHEM. WERNER HERTEL, D1PL.-PHYS.
MANDA-TAIRCS AGRi£s PRES U'OFFICE EUROPREN DES BREVETSMANDA-TAIRCS AGRi £ s PRES U'OFFICE EUROPREN DES BREVETS
κ 1521 t5 Okt. MO κ 1521 t5 Oct. MO
KRKA
Novo Mesto / JugoslawienKRKA
Novo Mesto / Yugoslavia
Verfahren zur Herstellung von (2S)-6-[ (Aminophenylacetyl)-amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclol[3.2.0]heptan-2-carbonsäure-1,S-dihydro-S-oxo-i-isobenzofurany!ester Process for the preparation of (2S) -6- [(aminophenylacetyl) -amino] -3,3-dimethyl-7-oxo-4-thia-1-azabicyclol [3.2.0] heptane-2-carboxylic acid-1, S- dihydro-S-oxo-i-isobenzofurany! ester
130019/0704130019/0704
β MÜNCHEN 86, SIEBERTSTR. 4 - POB 860720 · KABEL: MUEBOPAT · TEL. (089) 474005 · TELECOPIER XEROX 400 ■ TELEX 5-24 28Sβ MUNICH 86, SIEBERTSTR. 4 - POB 860720 CABLE: MUEBOPAT TEL. (089) 474005 · TELECOPIER XEROX 400 ■ TELEX 5-24 28S
Verfahren zur Herstellung von (2S)-f.-[(Aminophenylacetyl)-amino]-313-dimethyl-7-oxo-4-thia-1-azabicycloC3.2.0]heptan-2-carbonsäure-1,3~dihydro-3-oxo-1-isobenzofuranylester Process for the preparation of (2S) -f .- [(aminophenylacetyl) -amino] -3 1 3-dimethyl-7-oxo-4-thia-1-azabicycloC3.2.0] heptane-2-carboxylic acid-1,3-dihydro -3-oxo - 1-isobenzofuranyl ester
Die vorliegende Erfindung betrifft ein neues Verfahren zur Herstellung des (2S)-6-[(Aminophenylacetyl)-amino]-3,3-dimethyl-7"Oxo-4-thia-1-azabicycloC3.2.0]heptan-2-carbonsäure-1,3-dihydro-3-oxo-1-isobenzofuranylesters der Formel IThe present invention relates to a new method for Preparation of (2S) -6 - [(aminophenylacetyl) -amino] -3,3-dimethyl-7 "Oxo-4-thia-1-azabicycloC3.2.0] heptane-2-carboxylic acid-1,3-dihydro-3- oxo-1-isobenzofuranyl ester of formula I.
CH-COlTHCH-COlTH
und dessen pharmazeutisch annehmbarer Salze.and its pharmaceutically acceptable salts.
Die Verbindung der Formel I wird erfindungsgemäss derart hergestellt, dass man den e-Aminopenicillansäure-ijJ-dihydro-3~oxo-1-isobenzofuranylester der Formel IIAccording to the invention, the compound of formula I becomes such produced that the e-aminopenicillanic acid-ijJ-dihydro-3-oxo-1-isobenzofuranyl ester of formula II
S CH,NS,
-COO-COO
(II)(II)
mit dem 4-Phenylthiazolidin-2,5~dion der Formel IIIwith the 4-phenylthiazolidine-2,5-dione of the formula III
130019/0704130019/0704
(III)(III)
kondensiert.condensed.
Die Kondensation wird in vasserniEchbaren Lösungsmitteln, vorzugsweise in AcetonA'asser in volumetrischem Verhältnis von 7:2 bis 7:5, bei einem pH-Wert von 6,2 bis 8,0 unter Kühlen, vorzugsweise bei einer Temperatur von ~5 bis 1O0C, ausgeführt. Das erhaltene Produkt wird in Form von pharmazeutisch verwendbaren Salzen nach schon bekannten Verfahren gereinigt und isoliert.The condensation is carried out in water-soluble solvents, preferably in acetone / water in a volumetric ratio of 7: 2 to 7 : 5, at a pH of 6.2 to 8.0 with cooling, preferably at a temperature of ~ 5 to 10 0 C, executed. The product obtained is purified and isolated in the form of pharmaceutically acceptable salts according to processes already known.
Die Verbindung der allgemeinen Formel I ist ein bekanntes halbsynthetisches Antibiotikum mit einem breiten antibakteriellen Wirkungsspektrum (Talampicillin), welches sich im Organismus in das Ampicillin hydrolysiert. Es wird peroral verabreicht und wird als solches zweimal schneller absorbiert und erzielt eine zweimal höhere Konzentration im Blut als eine äquivalente Dosis von Ampicillin. Die Verbindung ist in J.Ked.Chem. 1^, 1585 (1976) und J. Antibiot. 2£, 665 (197*0 beschrieben.The compound of the general formula I is a known one semi-synthetic antibiotic with a broad spectrum of antibacterial activity (talampicillin), which is found in the organism hydrolyzed into the ampicillin. It is administered orally and, as such, is absorbed and achieved two times faster a concentration in the blood twice higher than an equivalent dose of ampicillin. The connection is in J.Ked.Chem. 1 ^, 1585 (1976) and J. Antibiot. 2 £, 665 (197 * 0 described.
Gemäss den bisher bekannten Verfahren wird Talampicillin mittels Kondensation der r3aktiven Form des N-geschützten D-Phenylglycins und des 6-Hminopenicillans*aure-1l3~dinydro-2~oxo-1-isobenzofuranylesters gewonnen. Diese Verfahren sind zeitraubend, da man in der letzten Phase der Synthese die N-geschützten Gruppen vor der endgültigen Isolierung des Talampicillins chemisch beseitigen muss. Der Vorteil unseres Verfahrens besteht insbesondere in der chemischen und technologischen Einfachkeit, da beim Verfahren zur Synthese von Talampicillin gemass der vorliegenden Erfindung das 4-Phenylthiazolidin-2,5~dion verwendet wird, in welchem die funktionellen Carboxy- und Aminogruppen gleichzeitig geschützt undAccording to the previously known processes, talampicillin is obtained by condensation of the active form of the N-protected D-phenylglycine and the 6-hminopenicillan-acid-1 l 3-dinydro-2-oxo-1-isobenzofuranyl ester. These procedures are time consuming because the last phase of the synthesis requires chemical removal of the N-protected groups prior to the final isolation of the talampicillin. The advantage of our process consists in particular in the chemical and technological simplicity, since in the process for the synthesis of talampicillin according to the present invention the 4-phenylthiazolidine-2,5-dione is used, in which the functional carboxy and amino groups are protected and at the same time
130019/0 7 04130019/0 7 04
r-r-
für die Reaktion der Kondensation mit dem G-Aminopenicillsnsäure-phthalidylester entsprechend aktiviert sind. Nach "beendeter Kondensation wird das Endprodukt Talampicillin ohne chemische Nachbehandlungen, die bei bisher bekannten Verfahren unumgänglich waren, gewonnen.for the reaction of the condensation with the G-aminopenicillic acid phthalidyl ester are activated accordingly. When the condensation is complete, the end product becomes talampicillin obtained without chemical post-treatment, which was inevitable with previously known processes.
Das Verfahren wird durch die folgenden Ausführungsbeispiele näher erläutert, jedoch keineswegs eingeschränkt.The method is carried out by the following working examples explained in more detail, but in no way restricted.
0,385 E (0,001 Mol) 6-Aminopenicillansäure-i,,3-dihydro-3-oxo-1-isobenzofuranylester.Hydrochlorid werden in einem Gemisch aus 5 ml" Aceton und 2 ml Wasser bei einer Temperatur von 2 bis 3 C gelöst. Die derart erhaltene Lösung wird unter Rühren mit einer Lösung von 0,193 g (0,001 Mol) 4-Phenylthiazolidin-2,5~dion in 2,5 ^l wässerigem Aceton (5 %iger Vassergehalt) versetzt» Das Reaktionsgemisch wird bei derselben Temperatur 40 Minuten bei einem pH-Wert von 7,2 bis 7,6 weitergerührt, , der pH-Wert wird mittels 4 N HGl auf 6,2 eingestellt und bei derselben Temperatur noch 1 Stunde weitergerührt. Nach beendeter Reaktion wird mit 10 ml Wasser versetzt und mittels 4 N HCl auf einen pH-Wert von 2 angesäuert. Die wässerige Lösung wird mehrnals mit Athylacetat gewaschen und mit 4 g NaCl versetzt, so dass sich das öl abscheidet, welches zweimal mit 10 ml Methylenchlorid extrahiert wird. Die vereinigten organischen Schichten werden mit einer 15 %igen wässerigen NaCl-Lösung gewaschen, mit Na^SO^ getrocknet und filtriert. Es wird mit 8 ml Isopropanol versetzt und in Vakuum abdestilliert. Nach Entfernung der überwiegenden Menge, des CH2CIp beginnt sich das Produkt abzuscheiden. Das abgeschiedene Produkt wird über Nacht im Kühlschrank gelassen und anschliessend filtriert. Nach Trocknen im Vakuum (200 tabar) werden 2,33 G des Ampicillin-1,3~dihydro-3-oxo-1-benzofuranylester.Hydrochlorids erhalten (45 %ige Ausbeute).0.385 E (0.001 mol) of 6-aminopenicillanic acid-i ,, 3-dihydro-3-oxo-1-isobenzofuranyl ester. Hydrochloride are dissolved in a mixture of 5 ml of acetone and 2 ml of water at a temperature of 2 to 3 C. The The solution obtained in this way is mixed with a solution of 0.193 g (0.001 mol) of 4-phenylthiazolidine-2,5-dione in 2.5 ^ l aqueous acetone (5% water content) while stirring. The reaction mixture is at the same temperature for 40 minutes The pH is adjusted to 6.2 using 4N HGl and the mixture is stirred for a further 1 hour at the same temperature N HCl acidified to pH 2. The aqueous solution is washed several times with ethyl acetate and mixed with 4 g of NaCl, so that the oil separates out, which is extracted twice with 10 ml of methylene chloride % aqueous NaCl solution washed with Na ^ SO ^ ge dries and filtered. 8 ml of isopropanol are added and the mixture is distilled off in vacuo. After the majority of the CH 2 Clp has been removed, the product begins to separate out. The deposited product is left in the refrigerator overnight and then filtered. After drying in vacuo (200 tabar), 2.33 g of the ampicillin-1,3-dihydro-3-oxo-1-benzofuranyl ester hydrochloride are obtained (45% yield).
130019/0704130019/0704
Schmp. (Zers.) - 154 bic 1^8°CMp (dec.) - 154 bic 1 ^ 8 ° C
CaJ^0- +157°(1Vol.Aol., MeOH)CaJ ^ 0 - + 157 ° (1 vol. Aol., MeOH)
Jodometrißch ermittelter Gehalt 96,5 % Argentometrisch ermittelter Gehalt 97 % Mikrobiologisch ermittelter Gehalt 98 % Die IR und NMR Spektren entsprechen dem Standard Talmapicillin.HCl.Iodometrically determined content 96.5% Argentometrically determined content 97 % Microbiologically determined content 98% The IR and NMR spectra correspond to the standard Talmapicillin.HCl.
0»385 B (0,001 Mol) e-Aminopenicillansäure-I^J-dihydro-J-oxo-1-isobenzofuränyl-ester-Hydrochlorid -werden in 7 nl eines Gemisches aus Aceton:Wasser (5:2) "bei einer Temperatur von 0°C gelost. Die derart hergestellte Lösung wird mit einer vorbereiteten Losung von 4--Phenylthiazolidin-2,5~dion in 2 ml Aceton tropfenweise versetzt. Die Losung wird 1,5 Stunden bei derselben Temperatur und bei einem pH-Wert von 7 "bis 8 gerührt. Es wird mit 10 ml Wasser versetzt und das Aceton wird abdestilliert. Anschliessend wird mit 20 ml Sthylacetat versetzt und unter Rühren wird der pH-Wert mittels 2 η HCl auf 2 eingestellt. Die wässerige Schicht wird noch zweimal mit 20 ml Sthylacetat gewaschen. Es wird mit 4 g NaCl versetzt, um ein öl abzuscheiden, welches zweimal mit 10 ml Methylenchlorid extrahiert wird. Die vereinigten organischen Schichten werden mit einer 15 %igen wässerigen NaCl-Lösung gewaschen und mittels MgSO^ getrocknet. Das Trocknungsmittel wird abfiltriert und es wird mit 20 ml Äther versetzt. Der erhaltene Niederschlag wird filtriert und in Vakuum getrocknet (200 mbar). Es werden 2,08 g erhalten (40 %ige Ausbeute).0 »385 B (0.001 mol) e-aminopenicillanic acid-I ^ J-dihydro-J-oxo-1-isobenzofuränyl ester hydrochloride - are in 7 nl of a mixture of acetone: water (5 : 2)" at a temperature of 0 ° C. A prepared solution of 4-phenylthiazolidine-2,5-dione in 2 ml of acetone is added dropwise to the solution thus prepared "stirred to 8. 10 ml of water are added and the acetone is distilled off. Then 20 ml of stylacetate are added and the pH is adjusted to 2 by means of 2η HCl with stirring. The aqueous layer is washed two more times with 20 ml of stylacetate. 4 g of NaCl are added in order to separate out an oil, which is extracted twice with 10 ml of methylene chloride. The combined organic layers are washed with a 15% aqueous NaCl solution and dried using MgSO ^. The drying agent is filtered off and 20 ml of ether are added. The precipitate obtained is filtered and dried in vacuo (200 mbar). 2.08 g are obtained (40% yield).
Schmp. (Zers.) = 153 bis 157°CM.p. (dec.) = 153-157 ° C
Ca]p0= +158° (1 Vol.AoI, MeOH)Ca] p 0 = + 158 ° (1 vol. AoI, MeOH)
Jodometrisch-ermittelter Gehalt 95»5 % Argentometrisch"ermittelter Gehalt 98 % Mikrobiologisch ermittelter Gehalt 95 % Die IR und RMR Spektren entsprechen dem Standard Talampicillin.HCl.Iodometrically determined content 95 »5% Argentometrically" determined content 98 % Microbiologically determined content 95% The IR and RMR spectra correspond to the standard Talampicillin.HCl.
13 0019/070413 0019/0704
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU251679A YU41185B (en) | 1979-10-16 | 1979-10-16 | Process for preparing the 1,3-dimydro-3-oxo-1-isobenzofuranyl-ester of (2s)-6(amino-phenylacetyl)-amino)-3,3-dimethy-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3038950A1 true DE3038950A1 (en) | 1981-05-07 |
Family
ID=25558180
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19803038950 Withdrawn DE3038950A1 (en) | 1979-10-16 | 1980-10-15 | METHOD FOR PRODUCING (2S) -6- ((AMINOPHENYLACETYL) -AMINO) -3,3-DIMETHYL-7-OXO-4-THIA-1-AZABICYCLOL (3.2.0) HEPTAN-2-CARBONIC ACID-1,3- DIHYDRO-3-OXO-1-ISOBENZOFURANYLESTER |
Country Status (4)
| Country | Link |
|---|---|
| CH (1) | CH646703A5 (en) |
| DE (1) | DE3038950A1 (en) |
| FR (1) | FR2467853A1 (en) |
| YU (1) | YU41185B (en) |
-
1979
- 1979-10-16 YU YU251679A patent/YU41185B/en unknown
-
1980
- 1980-10-06 CH CH745980A patent/CH646703A5/en not_active IP Right Cessation
- 1980-10-10 FR FR8021660A patent/FR2467853A1/en not_active Withdrawn
- 1980-10-15 DE DE19803038950 patent/DE3038950A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| YU41185B (en) | 1986-12-31 |
| CH646703A5 (en) | 1984-12-14 |
| YU251679A (en) | 1982-10-31 |
| FR2467853A1 (en) | 1981-04-30 |
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