DE1966203A1 - New 2,3-Dioxo-4- (R ', R ") - aminomethyl-pyrrolidines and their production process - Google Patents

New 2,3-Dioxo-4- (R ', R ") - aminomethyl-pyrrolidines and their production process

Info

Publication number
DE1966203A1
DE1966203A1 DE19691966203 DE1966203A DE1966203A1 DE 1966203 A1 DE1966203 A1 DE 1966203A1 DE 19691966203 DE19691966203 DE 19691966203 DE 1966203 A DE1966203 A DE 1966203A DE 1966203 A1 DE1966203 A1 DE 1966203A1
Authority
DE
Germany
Prior art keywords
dioxo
pyrrolidine
radicals
radical
formula
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.)
Granted
Application number
DE19691966203
Other languages
German (de)
Other versions
DE1966203B2 (en
DE1966203C3 (en
Inventor
Rene Heymes
Jacques Martel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi Aventis France
Original Assignee
Roussel Uclaf SA
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Roussel Uclaf SA filed Critical Roussel Uclaf SA
Publication of DE1966203A1 publication Critical patent/DE1966203A1/en
Publication of DE1966203B2 publication Critical patent/DE1966203B2/en
Application granted granted Critical
Publication of DE1966203C3 publication Critical patent/DE1966203C3/en
Expired legal-status Critical Current

Links

Classifications

    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01H—ELECTRIC SWITCHES; RELAYS; SELECTORS; EMERGENCY PROTECTIVE DEVICES
    • H01H9/00—Details of switching devices, not covered by groups H01H1/00 - H01H7/00
    • H01H9/18—Distinguishing marks on switches, e.g. for indicating switch location in the dark; Adaptation of switches to receive distinguishing marks
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
    • C07D207/36—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
    • C07D207/36—Oxygen or sulfur atoms
    • C07D207/38—2-Pyrrolones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • C07D501/02—Preparation
    • C07D501/08—Preparation by forming the ring or condensed ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • C07D501/14—Compounds having a nitrogen atom directly attached in position 7
    • C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
    • C07D501/18—7-Aminocephalosporanic or substituted 7-aminocephalosporanic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • C07D501/14—Compounds having a nitrogen atom directly attached in position 7
    • C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
    • C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
    • C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
    • C07D501/38—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • C07D501/14—Compounds having a nitrogen atom directly attached in position 7
    • C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
    • C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
    • C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
    • C07D501/38—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof
    • C07D501/42—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof with the 7-amino radical acylated by an araliphatic carboxylic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F21—LIGHTING
    • F21V—FUNCTIONAL FEATURES OR DETAILS OF LIGHTING DEVICES OR SYSTEMS THEREOF; STRUCTURAL COMBINATIONS OF LIGHTING DEVICES WITH OTHER ARTICLES, NOT OTHERWISE PROVIDED FOR
    • F21V17/00—Fastening of component parts of lighting devices, e.g. shades, globes, refractors, reflectors, filters, screens, grids or protective cages
    • F21V17/10—Fastening of component parts of lighting devices, e.g. shades, globes, refractors, reflectors, filters, screens, grids or protective cages characterised by specific fastening means or way of fastening
    • F21V17/16—Fastening of component parts of lighting devices, e.g. shades, globes, refractors, reflectors, filters, screens, grids or protective cages characterised by specific fastening means or way of fastening by deformation of parts; Snap action mounting
    • G—PHYSICS
    • G09—EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09F—DISPLAYING; ADVERTISING; SIGNS; LABELS OR NAME-PLATES; SEALS
    • G09F9/00—Indicating arrangements for variable information in which the information is built-up on a support by selection or combination of individual elements
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01H—ELECTRIC SWITCHES; RELAYS; SELECTORS; EMERGENCY PROTECTIVE DEVICES
    • H01H13/00—Switches having rectilinearly-movable operating part or parts adapted for pushing or pulling in one direction only, e.g. push-button switch
    • H01H13/50—Switches having rectilinearly-movable operating part or parts adapted for pushing or pulling in one direction only, e.g. push-button switch having a single operating member
    • H01H13/52—Switches having rectilinearly-movable operating part or parts adapted for pushing or pulling in one direction only, e.g. push-button switch having a single operating member the contact returning to its original state immediately upon removal of operating force, e.g. bell-push switch

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • Theoretical Computer Science (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Cephalosporin Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

Dr. F. Zumstein sen. - Dr. E. Assmann Dr. R. Koenlgsberger - Dlpl.-Phys. R. Holzbauer - Dr. F. Zumstein Jun.Dr. F. Zumstein Sr. - Dr. E. Assmann Dr. R. Koenlgsberger - Dlpl.-Phys. R. Holzbauer - Dr. F. Zumstein Jun.

PATENTANWÄLTEPATENT LAWYERS

TELEFON: SAMMEL-NR. 22S341TELEPHONE: COLLECTIVE NO. 22S341

TELEX 529979 . TELEGRAMME: ZUMPAT POSTSCHECKKONTO: MÜNCHEN 91139TELEX 529979. TELEGRAMS: ZUMPAT POST CHECK ACCOUNT: MUNICH 91139

BANKKONTO: BANKHAUS H. AUFHÄUSERBANK ACCOUNT: BANKHAUS H. AUFHÄUSER

B MÜNCHEN 2,B MUNICH 2,

BRÄUHAUSSTRASSE 4/IIIBRÄUHAUSSTRASSE 4 / III

90/n90 / n

1265 Div./l/D-I1265 Div./l/D-I

ROUSSEL-UCLAF, Paris/FrankreichROUSSEL-UCLAF, Paris / France Neue 2,3-Dioxo-4- (R', R" y-aminomethyl-pyrrolic1:»* neNew 2,3-dioxo-4- (R ', R "y-aminomethyl-pyrrolic 1 :» * ne

und ihr Herstellungsverfahrenand their manufacturing process

[Ausscheidung aus Patent · ··· ... (Patentanmeldung P 19 32 504.3-44)] [Removal from patent · ··· ... (patent application P 19 32 504.3-44)]

Die Erfindung betrifft neue 2,3-Dioxo-4-(R',R")-aminomethyl- . pyrrolidine und ihr Herstellungsverfahren. ™The invention relates to new 2,3-dioxo-4- (R ', R ") - aminomethyl-. pyrrolidine and its manufacturing process. ™

Die Erfindung betrifft insbesondere 2,3-Dioxo-4-(R«,R")-aminomethyl-pyrrolidine der EnolformelThe invention relates in particular to 2,3-dioxo-4- (R «, R") - aminomethyl-pyrrolidines of the enol formula

CHO-N 2 CH O -N 2

LrLr

in der R. Wasserstoff, einen Alkylrest oder einen AryLrest bedeutiit und diese Reste substituiert oder unsubsti tuiejrt sein köntit-.ü^ U' und R" AlkyL- od«r AraLkyLrtJiiLe d.-irytol Li»ri oclnrbe R. is hydrogen, an alkyl radical or an aryl radical and deutiit be substituted for these radicals tuiejrt or unsubsti köntit-ever tried g ^ U 'and R "are alkyl od" r AraLkyLrtJiiLe d.-irytol Li "ri oclnr

, y i} ., nHn 7 :, n BAD ORIGINAL, y i} ., nHn 7 :, n BAD ORIGINAL

zusammen einen heterocyclischen Rest bilden.together form a heterocyclic radical.

Diese Verbindungen eignen sich zur vorteilhaften Herstellung von neuen Cephalosporinvorprodukten gemäß Patent . ... ... (Patentanmeldung P 19 32 504.3-44, die dann zu den Cephalosporinendprodukten gemäß der offengelegten holländischen Patentanmeldung Nr. 68-00751 führen. Wie in dieser Patentanmeldung ausgeführt, besitzen diese Cephalosporinderivate interessante antibiotische Eigenschaften.These compounds are suitable for advantageous production of new cephalosporin precursors according to patent. ... ... (patent application P 19 32 504.3-44, which then becomes the cephalosporin end products according to laid-open Dutch patent application No. 68-00751. As in this patent application carried out, these cephalosporin derivatives have interesting antibiotic properties.

Das Herstellungsverfahren für die neuen 2,3~Dioxo-4-(R·,R")-aminomethyl-pyrrolidine der angegebenen Formel, Gegenstand der vorliegenden Erfindung, ist dadurch gekennzeichnet, daß man einen 2,3-Dioxo-pyrrolidin-4-carbonsäure-benzylester der EnolformelThe manufacturing process for the new 2,3 ~ Dioxo-4- (R ·, R ") - aminomethyl-pyrrolidine of the formula given, the subject of the present invention, is characterized in that a 2,3-dioxopyrrolidine-4-carboxylic acid benzyl ester of Enol formula

C00CHoCcHc C00CH o C c H c

einer katalytischen Hydrierung unterwirft, dabei das entspre chende 4-Carboxylderivat der Formelsubject to a catalytic hydrogenation, the corresponding corresponding 4-carboxyl derivative of the formula

COOHCOOH

erhält, das man einer Aminomethylierung nach Mannich unterwirft und das gesuchte Aminomethyl-pyrrolidin isoliert.obtained, which is subjected to an aminomethylation according to Mannich and the sought aminomethyl-pyrrolidine is isolated.

Das erfindungsgemäße Verfahren, wie es oben definiert wurde, umfaßb insbesondere eine bemerkenswerte, nicht naheliegende Ph as ο:The method according to the invention, as defined above, In particular, it includes a notable, non-obvious one Ph as ο:

BAD BA D

■· ■ '· ■■ .« ü ■ -, ' 1 ■.■ · ■ '· ■■. «Ü ■ -,' 1 ■.

Die Hydrogenolyse des 2,3-Dioxo-pyrrolidin-4-carbonsäurebenzylesters der Enolformel durch katalytische Hydrierung, die die 3,4-Doppelbindung bestehen läßt, wobei dieser Hydrogenolyse eine Decarboxylierung im Milieu der Aminomethylierung folgt.The hydrogenolysis of the 2,3-dioxopyrrolidine-4-carboxylic acid benzyl ester the enol formula by catalytic hydrogenation, which allows the 3,4 double bond to exist, this hydrogenolysis a decarboxylation in the aminomethylation environment follows.

Man beachte, daß in dem besonderen Fall, wo R- = H, die einfache Eliminierung der Carboxylgruppe, die für die Schaffung einer aktivierten Methylengruppe (daher alkylierbar) in der 4-Stellung nützlich ist, bisher nicht durchgeführt werden konnte, ohne die heterocyclische Verkettung zu zerbrechen [vgl. Southwick et coll., J.Org* 21., 1086 <1956)].Note that in the particular case where R- = H, the simple Elimination of the carboxyl group responsible for the creation of an activated methylene group (therefore alkylatable) in the 4-position is useful, has not yet been carried out could without breaking the heterocyclic chain [cf. Southwick et coll., J.Org * 21., 1086 <1956)].

Die beim erfindungsgemäßen Verfahren einzusetzenden Ausgangsstoffe werden gemäß Patent . ... ..« (Patentanmeldung P 19 32 504.3-44) hergestellt, indem man eine Aminosäure der FormelThe starting materials to be used in the process according to the invention are according to patent. ... .. «(patent application P 19 32 504.3-44) prepared by adding an amino acid of the formula

R1HN - CH2 - CH2 - COOHR 1 HN - CH 2 - CH 2 - COOH

mit Benzylalkohol in Gegenwart eines sauren Mittels der Formel HX umsetzt, in der X ein Halogen-, Schwefelsäure- oder Sulfonsäureanion darstellt, ein Estersalz der Formelwith benzyl alcohol in the presence of an acidic agent of the formula HX, in which X is a halogen, sulfuric acid or sulfonic acid anion represents an ester salt of the formula

Θ.Θ.

R11H0N - CH0 - CH0 - COO - CHOCCH,-1 c ί d coo R 11 H 0 N - CH 0 - CH 0 - COO - CH O C C H, -1 c ί d coo

erhält, das man mit einem Oxalsäurealkyl- oder -aralkylester kondensiert, wobei man den gewünschten 2,3-Dioxo-pyrrolidin-4—carbonsäure—benzylester mit der Enolformelobtained, which is condensed with an oxalic acid alkyl or aralkyl ester to give the desired 2,3-dioxopyrrolidine-4-carboxylic acid benzyl ester with the enol formula

COO-CHn-CcH1-2 obCOO-CH n -CcH 1 -2 ob

erhält.receives.

109885/1799109885/1799

Eine bevorzugte Ausführungsform des erfindungsgemäßen Verfahrens, die jedoch keinen einschränkenden Charakter haben soll, kann im einzelnen durch die folgenden Punkte gekennzeichnet werden!A preferred embodiment of the method according to the invention, which, however, is not intended to be of a restrictive nature, can be identified in detail by the following points will!

- Die Hydrogenolyse des 2,3-Dioxo-pyrrolidin-4-carbonsäurebenzylesters der Enolformel wird in Gegenwart eines Hydrierkatalysators auf der Basis von Palladium oder Platin durchgeführt. - The hydrogenolysis of the 2,3-dioxopyrrolidine-4-carboxylic acid benzyl ester the enol formula is carried out in the presence of a hydrogenation catalyst based on palladium or platinum.

- Die Aminomethylierung des Produktes der Hydrogenolyse wird durch Einwirkung von Formaldehyd und dem Hydrochlorid des gewählten Amins durchgeführt, wobei man in Chlorwasserstoffsaurem Milieu arbeitet. Als Beispiele für Amine seien Morpholin, Pyrrolidin, Dimethylamin, Diethylamin etc. genannt.- The aminomethylation of the product of hydrogenolysis is carried out by the action of formaldehyde and the hydrochloride of the selected amine, being carried out in hydrochloric acid Milieu works. Morpholine, pyrrolidine, dimethylamine, diethylamine, etc. may be mentioned as examples of amines.

Das folgende Beispiel erläutert die Erfindung, ohne sie jedoch einzuschränken.The following example explains the invention without, however, restricting it.

Beispielexample

1. Stufe: 21S-Dioxo-pyrrolidin-^carbonsäure1st stage: 2 1 S-dioxo-pyrrolidine- ^ carboxylic acid

a) Herstellung des Hydrierkatalysatorsa) Preparation of the hydrogenation catalyst

Man rührt unter Wasserstoffatmosphäre eine Suspension von 0,8 g Tierkohle in 4 ecm einer wäßrigen 2%-igen Palladiumchloridlösung. Nach der Sättigung des Katalysators saugt man ihn unter Luftausschluß ab und spült mehrmals mit wasserfreiem Dimethylformamid.A suspension of 0.8 g of animal charcoal in 4 cm of an aqueous 2% palladium chloride solution is stirred under a hydrogen atmosphere. After the catalyst is saturated, it is suctioned off with exclusion of air and rinsed several times with anhydrous Dimethylformamide.

b) Hydrierungb) hydrogenation

Man löst 9,32 g 2,3-Dioxo-pyrrolidin-4-carbonsäure-benzylester in 50 ecm wasserfreiem Dimethylformamid, fügt den oben hergestellten Katalysator hinzu. Man setzt das Ganze unter Wasserstoffatmosphäre, rührt dann und kühlt von Zeit zu Zeit, um jegliche spürbare Temperaturerhöhung zu vermeiden. Man filtriert, fügt 500 ecm Isopropyläther zum Filtrat, saugt ab und trocknet.9.32 g of benzyl 2,3-dioxopyrrolidine-4-carboxylate are dissolved in 50 ecm of anhydrous dimethylformamide, the above is added added catalyst produced. Put the whole thing under a hydrogen atmosphere, then stir and cool from time to time, to avoid any noticeable increase in temperature. It is filtered, 500 ecm of isopropyl ether is added to the filtrate, and it is filtered off with suction dries.

109885/1799109885/1799

19652031965203

Man erhält 4,618 g (96 %) Produkt, das man so, wie es ist, für die weitere Synthese verwendet. Für die Analyse löst man es in 6 Volumina Dimethylsulfoxyd und 4 Volumina Methanol. Man filtriert und fügt erneut 4 Volumina Methanol hinzu. Es bildet sich ein weißer Niederschlag, den man absaugt und trocknet. Ausbeute bei der Reinigung: 60 %.4.618 g (96 %) of product are obtained, which product is used as it is for the further synthesis. For analysis, it is dissolved in 6 volumes of dimethyl sulfoxide and 4 volumes of methanol. It is filtered and another 4 volumes of methanol are added. A white precipitate forms, which is filtered off with suction and dried. Purification yield: 60%.

Das Produkt liegt in Form weißer Kristalle vor, die wegen Decarboxylierung wenig stabil sind. Es ist löslich in Dimethylsulfoxyd und Dimethylformamid, unlöslich in Isopropyläther und Wasser.The product is in the form of white crystals due to decarboxylation are not very stable. It is soluble in dimethyl sulfoxide and dimethylformamide, insoluble in isopropyl ether and water.

IR-Spektrum (in Nujol): IR spectrum (in Nujol):

Absorption im Bereich von assoziiertem OH/nh Komplexe und starke Absorption im CarboxyIbereich: Schulter 1708 cm max. 1677 cm ,Absorption in the area of associated OH / nh complexes and strong absorption in the carboxy area: Shoulder 1708 cm max. 1677 cm,

Analyse: C5H5O4N Analysis: C 5 H 5 O 4 N

Berechnet: C 41,96 H 3,52 N 9,79 % Gefunden: 41,7 3,8 9,9Calculated: C 41.96 H 3.52 N 9.79 % Found: 41.7 3.8 9.9

Soweit bekannt, ist diese Verbindung in der Literatur nicht beschrieben.As far as is known, this compound is not described in the literature.

2. Stufe: Hydrochlorid des 2v3-»Dioxo-4-morpholino-methyl~ pyrrolidins mit R'+Rn»CH2CH2-O-CH2-CH2 und R1-H 2nd stage: hydrochloride of 2 v 3- »dioxo-4-morpholino-methyl ~ pyrrolidine with R '+ R n » CH 2 CH 2 -O-CH 2 -CH 2 and R 1 -H

Man fügt 2 Tropfen ln-Chlorwasserstoffsäure zu 10 ecm einer Morpholin-hydrochloridlösung, die durch Neutralisation von 8,71 g Morpholin mit konzentrierter Chlorwasserstoffsäure und Zugabe von 50 ecm Wasser hergestellt worden war. Man fügt 2 ecm 30%-igen Formaldehyd hinzu und trägt dann 2,83 g 2,3-Dioxo-pyrrolidin-4-carbonsäure ein. Die Reaktionsmischung wird unter Rühren 30 Stunden lang auf 60 bis 65°C erhitzt. Man dampft zur Trockne ein und kristallisiert den Rückstand in Xthanol um. Man erhält 2,986 g Produkt, das direkt für die weitere Synthese brauchbar ist»2 drops of 1N hydrochloric acid are added to each 10 ecm Morpholine hydrochloride solution obtained by neutralizing 8.71 g of morpholine with concentrated hydrochloric acid and adding 50 ecm of water. One adds 2 ecm of 30% formaldehyde is added and then carries 2.83 g of 2,3-dioxopyrrolidine-4-carboxylic acid a. The reaction mixture is heated to 60 to 65 ° C. for 30 hours with stirring. Man evaporated to dryness and the residue recrystallized in ethanol. 2.986 g of product are obtained, which is used directly for the further synthesis is useful »

10988S/179910988S / 1799

Zwecks Analyse löst man das Produkt in 1 Volumen heißen Wassers und fügt 3 Volumina Äthanol hinzu. Man stellt in Eis, saugt ab und erhält mit einer Ausbeute von 80 % ein Produkt, das in Form weißer Kristalle vorliegt, wenig löslich in Äthanol und Äther, löslich in Wasser.For analysis, the product is dissolved in 1 volume of hot water and 3 volumes of ethanol are added. One puts in Ice, sucks off and, with a yield of 80%, obtains a product which is in the form of white crystals and is sparingly soluble in ethanol and ether, soluble in water.

Analyse; CgH15O3N2Cl » 234,7 Analysis; CgH 15 O 3 N 2 Cl »234.7

Berechnet: C 46,06 H 6,44 N 11,94 Cl 15,11 % Gefunden: 45,8 .6,4 11,8 15,2Calculated: C 46.06 H 6.44 N 11.94 Cl 15.11 % Found: 45.8, 6.4, 11.8, 15.2

IR-Spektrum in Nujol: IR spectrum in Nujol:

Absorptionsbanden bei 321O cm"" und 3,6 bis 4,1 μ Absorbance bands at 3210 cm "" and 3.6 to 4.1 µ

-1 ' Triplett im Carbonylbereich 1711 cm-1 ' triplet in the carbonyl region 1711 cm

1691 cm"1 1664 cm"1 1691 cm " 1 1664 cm" 1

Soweit bekannt, ist diese Verbindung in der Literatur nicht beschrieben.As far as is known, this compound is not described in the literature.

Das Hydrochlorid des 2,3-Dioxo-4-morpholino-methyl-pyrrolidins kann ausgehend von 2,3—Dioxo-pyrrolidin-4-carbonsäure-benzylester ohne Isolierung der zwischendurch auftretenden freien Säure auf folgende Weise erhalten werden:The hydrochloride of 2,3-dioxo-4-morpholino-methyl-pyrrolidine can be prepared from 2,3-dioxo-pyrrolidine-4-carboxylic acid benzyl ester can be obtained in the following manner without isolating the free acid which occurs in between:

Man trägt 30,33 g 2,3-Dioxo-pyrrolidin-4-carbonsäure-benzylester in 300 ecm Dioxan mit 10 % Wasser ein, erhitzt leicht, um das Produkt zu lösen, fügt 3 g Tierkohle und 1 ecm einer wäßrigen 20%-igen Palladiumchloridlösung hinzu, man setzt unter Wasserstoffatmosphäre und rührt sehr energisch. In 1 Stunde und 40 Minuten werden 2700 ecm Wasserstoff absorbiert (theoretisches Volumen: 2912 ecm). Man kühlt ab, spült mit Stickstoff und leitet dann 130 ecm der wie folgt zusammengesetzten Mischung ein:30.33 g of 2,3-dioxopyrrolidine-4-carboxylic acid benzyl ester in 300 ecm of dioxane with 10 % water are added, the mixture is heated slightly to dissolve the product, 3 g of animal charcoal and 1 ecm of an aqueous 20% - igen palladium chloride solution is added, the mixture is placed under a hydrogen atmosphere and stirred very vigorously. In 1 hour and 40 minutes, 2700 ecm of hydrogen are absorbed (theoretical volume: 2912 ecm). It is cooled, flushed with nitrogen and then introduced 130 ecm of the mixture composed as follows:

109885/1799109885/1799

Morpholin 43,5 gMorpholine 43.5 g

Wasser 100 ecmWater 100 ecm

konzentrierte ChlorwasserstoffsSure 40 ecm ln-Chlorwasserstoffsäure 15 ecmconcentrated hydrochloric acid 40 ecm In-hydrochloric acid 15 ecm

Formaldehyd 50 ecmFormaldehyde 50 ecm

Wasser zur Ergänzung auf 500 ecmWater to supplement to 500 ecm

Man erhitzt die Reaktionsmischung auf ungefähr 50 C und fängt innerhalb 1 Stunde 2325 ecm Kohlendioxydgas auf. Theoretisch müßte so viel Kohlendioxyd entwickelt werden, wie anfangs in der Reaktion Wasserstoff absorbiert wurde. Man erwartet daher höchstens die Entwicklung von 2700 ecm Kohlendioxydgas. Man rührt leicht einige Minuten, filtriert und dampft im Vakuum zur Trockne ein. Der Rückstand kann so, wie er ist, für die weitere Synthese verwendet werden.The reaction mixture is heated to about 50 ° C. and 2325 ecm of carbon dioxide gas is collected within 1 hour. Theoretically as much carbon dioxide would have to be evolved as hydrogen was initially absorbed in the reaction. One therefore expects at most the development of 2700 ecm of carbon dioxide gas. The mixture is stirred gently for a few minutes, filtered and evaporated in vacuo dry up. The residue can be used as it is for further synthesis.

Zwecks Analyse teigt man das erhaltene Produkt ml t Xthanol an, spült mit Äther, trocknet und erhält mit einer Ausbeute von 63,5 % ein Produkt, das mit dem oben beschriebenen identisch ist.For the purpose of analysis, the product obtained is made into a paste in ml of ethanol, rinsed with ether, dried and, with a yield of 63.5 %, a product is obtained which is identical to that described above.

Herstellung des AusqanqsmaterialsProduction of the starting material Stufe A; p-Toluolsulfonat des ß-AlaninbenzylestersLevel A; p-Toluenesulfonate of the ß-alanine benzyl ester

In eine Apparatur, die mit einem Wasserabscheider für die azeotrope Entfernung von in der Reaktion gebildetem Wasser versehen ist, erhitzt man die folgende Mischung 5 Stunden lang am Rückfluß:In an apparatus equipped with a water separator for the azeotropic removal of water formed in the reaction is provided, the following mixture is refluxed for 5 hours:

ß-Alanin 89 gβ-alanine 89 g

p-Toluolsulfonsäure-monohydrat 210 gp-toluenesulfonic acid monohydrate 210 g

Benzylalkohol 450 ecmBenzyl alcohol 450 ecm

Tetrachlorkohlenstoff 500 ecmCarbon tetrachloride 500 ecm

Während dieser Zeit wurden ungefähr 45 ecm Wasser abgeschieden. Die Reaktionsflüssigkeit wird anschließend durch Destillation im Vakuum auf ein kleines Volumen eingeengt; man kühlt ab und kristallisiert das gebildete Produkt in Äther. ManDuring this time approximately 45 ecm of water was separated out. The reaction liquid is then concentrated to a small volume by distillation in vacuo; one cools and the product formed crystallizes in ether. Man

109885/1799109885/1799

stellt in Eis, saugt ab, trocknet und gewinnt 35Og (entspricht einer quantitativen Ausbeute) Kristalle, f· = 142°C.puts in ice, sucks off, dries and wins 35Og (corresponds to a quantitative yield) crystals, f = 142 ° C.

Das erhaltene Produkt ist identisch mit dem von Nobuo Yzumiya et coll., Nippon Kagaku Zasshi 78, 662 (1957) beschriebenen.The product obtained is identical to that described by Nobuo Yzumiya et coll., Nippon Kagaku Zasshi 78, 662 (1957).

Stufe Bt 2«3-Dioxo~pyrrplidin-4--carbonsäure-benzylesterStage Bt 2 «3-Dioxo ~ pyrrplidin-4-carboxylic acid benzyl ester

Man trägt 225 g Kalium-tert.-butylat in 900 ecm wasserfreies Benzol ein, fügt 500 ecm Benzylalkohol hinzu, kühlt die Mischung in einem Eis/Methanol-Bad ab und gibt, ohne 300C zu überschreiten, 351 g p-Toluolsulfonat des ß-Alaninbenzylesters hinzu.225 g of potassium tert-butoxide are introduced into 900 ecm of anhydrous benzene, 500 ecm of benzyl alcohol are added, the mixture is cooled in an ice / methanol bath and, without exceeding 30 ° C., 351 g of p-toluenesulfonate are added ß-alanine benzyl ester added.

Andererseits löst man 300 g Oxa 1 säur e-benzyl erster in 600 ecm heißem Benzol, läßt auf Raumtemperatur zurückkommen und neutralisiert die schwache Azidität der Lösung durch Zugabe von 0,4 ecm Triethylamin. Diese Lösung gibt man zu der oben gebildeten Mischung und hält immer im Kühlbad. Man erwärmt wieder auf Raumtemperatur und bringt 5 Stunden lang zum Rückfluß.On the other hand, you dissolve 300 g of Oxa 1 acid e-benzyl first in 600 ecm hot benzene, allow to return to room temperature and neutralize the weak acidity of the solution by adding 0.4 cc triethylamine. This solution is added to the one formed above Mix and always keep in the cooling bath. The mixture is warmed back to room temperature and refluxed for 5 hours.

Man verjagt das Benzol im Vakuum, fügt nacheinander zuerst 2 Wasser, das 15 ecm Essigsäure enthält, dann 1,5 1 Isopropyläther und schließlich 110 ecm konzentrierte Chlorwasserstoffsäure hinzu (bis man einen pH von 1 erhält). Man stellt unter Rühren 2 l/2 Stunden lang in Eis. Man saugt ab, wäscht mit Wasser, mit Isopropyläther und kristallisiert durch Auflösen in Dimethylformamid und Ausfällen mit Wasser um. Man erhält 130,5 g (56 %) Produkt, F = 186°C, löslich in Alkoholen, Äther und Aceton, unlöslich in Benzol und Wasser.One chased the benzene in vacuo, added successively 2 first water containing 15 cc of acetic acid, then 1.5 1 of isopropyl ether and then 110 cc of concentrated hydrochloric acid added (up to a p H of 1 obtained). Place in ice for 2 1/2 hours with stirring. It is filtered off with suction, washed with water, with isopropyl ether and recrystallized by dissolving in dimethylformamide and precipitating with water. 130.5 g (56 %) of product are obtained, melting point 186 ° C., soluble in alcohols, ether and acetone, insoluble in benzene and water.

Analyse; C12H11O4N =233,24 Analysis; C 12 H 11 O 4 N = 233.24

Berechnet: C 61,8 H 4,76 N 6,01 %
Gefunden: 62 5,1 6,3Calculated: C 61.8 H 4.76 N 6.01%
Found: 62 5.1 6.3

IR-Spektrum:IR spectrum:

Zwei Maxima im Carbonylgebiet 1729 cm""1 und 1693 cm""1 Absorption im Gebiet von assoziiertem OH/nh Aromatisch monosubstituiert vorhanden.Two maxima in the carbonyl region 1729 cm "" 1 and 1693 cm "" 1 absorption in the region of associated OH / nh aromatic monosubstituted present.

109885/1799109885/1799

196S203196S203

Soweit bekannt, ist diese Verbindung in der Literatur nicht beschrieben.As far as is known, this compound is not described in the literature.

J O 9 Q 8 «» M 7 D 9J O 9 Q 8 «» M 7 D 9

Claims (8)

'«♦♦41··.-'«♦♦ 41 ·· .- 90/Ν 8. Juli 197190 / Ν July 8, 1971 (2/2/Ι)(2/2 / Ι) Betrifft; Patentanmeldung P 19 66 203.4 - (Ausscheidung aus Patentanmeldung P 19 32 504.3-44) ROUSSEL-UCLAF Gas 1265 Div./l/D-IRegards; Patent application P 19 66 203.4 - (separation from patent application P 19 32 504.3-44) ROUSSEL-UCLAF Gas 1265 Div./l/D-I PatentansprücheClaims Verfahren zur Herstellung eines 2,3-Dioxo-4-(R*,R'O-aminomethyl-pyrrolidins der EnolformelProcess for the preparation of a 2,3-Dioxo-4- (R *, R'O-aminomethyl-pyrrolidins the enol formula HOHO in der R1 Wasserstoff, einen Alkylrest oder einen Arylrest darstellt und diese Reste substituiert oder unsubstituiert sein können, R1 und R" Alkyl- oder Aralkylreste bedeuten oder zusammen einen heterocyclischen Rest bilden, dadurch gekennzeichnet, daß man einen 2,3-Dioxo-pyrrolidin—4-carbonsäurebenzylester der Enolformelin which R 1 represents hydrogen, an alkyl radical or an aryl radical and these radicals can be substituted or unsubstituted, R 1 and R "represent alkyl or aralkyl radicals or together form a heterocyclic radical, characterized in that a 2,3-dioxo benzyl pyrrolidine-4-carboxylate of the enol formula COOCH2C6H5 COOCH 2 C 6 H 5 einer katalytischen Hydrierung unterwirft, dabei das entsprechende 4-Carboxylderivat der Formelsubjected to a catalytic hydrogenation, the corresponding 4-carboxyl derivative of the formula COOH
HOCOOH
HO 1 0 9!) 8 5 / t 7 J Η 1 0 9!) 8 5 / t 7 yrs ^- ly^'is ."„■'»" Viii».-- ..^ - ly ^ 'is. ""■'»" Viii »- .. erhält, das man einer Aminomethylierung nach Mannich unterwirft und das gesuchte Aminomethylpyrrolidin isoliert.obtained, which is subjected to an aminomethylation according to Mannich and the sought aminomethylpyrrolidine is isolated. 2.) 2,3-Dioxo-pyrrolidin-4-carbonsäure-benzylester der Enolformel 2.) 2,3-Dioxopyrrolidine-4-carboxylic acid benzyl ester of the enol formula COOCH2C6H5 COOCH 2 C 6 H 5 in der R^ Wasserstoff, einen Alkylrest oder einen Arylrest darstellt und diese Reste substituiert oder unsubstituiert sein können.in which R ^ is hydrogen, an alkyl radical or an aryl radical represents and these radicals can be substituted or unsubstituted. 3.) 2,3-Dioxo~pyrrolidin-carbonsäure-benzylester.3.) 2,3-Dioxo-pyrrolidine-carboxylic acid benzyl ester. 4.) 2,3—Dioxo-pyrrolidin-4-carbonsäuren der Enolformel4.) 2,3-Dioxo-pyrrolidine-4-carboxylic acids of the enol formula COOHCOOH in der R1 Wasserstoff, einen Alkylrest oder einen Arylrest darstellt und diese Reste substituiert oder unsubstituiert sein können.in which R 1 represents hydrogen, an alkyl radical or an aryl radical and these radicals can be substituted or unsubstituted. 5.) 2,3-Dioxo-pyrrolidin-4-carbonsäure.5.) 2,3-Dioxo-pyrrolidine-4-carboxylic acid. 109885/1799109885/1799 6.) 2,3-Dioxo-4-(R1,R")-aminoraethy!-pyrrolidine der Enolformel6.) 2,3-Dioxo-4- (R 1 , R ") - aminoraethy! -Pyrrolidines of the enol formula in der R^ Wasserstoff, einen Alkylrest oder einen Arylrest bedeutet und diese Reste substituiert oder unsubstituiert
sein können, R1 und R" Alkyl- oder Aralkylreste darstellen oder zusammen einen heterocyclischen Rest bilden.in which R ^ denotes hydrogen, an alkyl radical or an aryl radical and these radicals are substituted or unsubstituted
R 1 and R "represent alkyl or aralkyl radicals or together form a heterocyclic radical. 7.) 2,3-Dioxo-4-morpholino-methyl~pyrrolidin und sein Hydrochlorid. 7.) 2,3-Dioxo-4-morpholino-methyl-pyrrolidine and its hydrochloride. 109885/1799109885/1799
DE1966203A 1968-06-27 1969-06-26 2,3-Dioxo-4- (R ', R ") - aminomethylpyrrolidines and process for their preparation Expired DE1966203C3 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR156898 1968-06-27

Publications (3)

Publication Number Publication Date
DE1966203A1 true DE1966203A1 (en) 1972-01-27
DE1966203B2 DE1966203B2 (en) 1980-02-07
DE1966203C3 DE1966203C3 (en) 1980-10-09

Family

ID=8651750

Family Applications (4)

Application Number Title Priority Date Filing Date
DE19691932498 Withdrawn DE1932498A1 (en) 1968-06-27 1969-06-26 New cephalosporin derivatives and their manufacturing process
DE19691966204 Pending DE1966204A1 (en) 1968-06-27 1969-06-26 New 1,3-thiazine derivatives
DE1967030A Expired DE1967030C3 (en) 1968-06-27 1969-06-26 γ-lactams of 6H, 7H-cis-7-amino-3aminomethyl-ceph-3-em-4-carboxylic acids
DE1966203A Expired DE1966203C3 (en) 1968-06-27 1969-06-26 2,3-Dioxo-4- (R ', R ") - aminomethylpyrrolidines and process for their preparation

Family Applications Before (3)

Application Number Title Priority Date Filing Date
DE19691932498 Withdrawn DE1932498A1 (en) 1968-06-27 1969-06-26 New cephalosporin derivatives and their manufacturing process
DE19691966204 Pending DE1966204A1 (en) 1968-06-27 1969-06-26 New 1,3-thiazine derivatives
DE1967030A Expired DE1967030C3 (en) 1968-06-27 1969-06-26 γ-lactams of 6H, 7H-cis-7-amino-3aminomethyl-ceph-3-em-4-carboxylic acids

Country Status (14)

Country Link
JP (2) JPS4934999B1 (en)
AT (2) AT293614B (en)
BE (1) BE735127A (en)
BR (3) BR6910252D0 (en)
CH (3) CH515276A (en)
DE (4) DE1932498A1 (en)
ES (2) ES368820A1 (en)
FR (1) FR1584569A (en)
GB (5) GB1271015A (en)
HU (1) HU162644B (en)
IL (1) IL32379A (en)
NL (2) NL142691B (en)
PL (1) PL79142B1 (en)
SU (2) SU495841A3 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4860900A (en) * 1986-08-19 1989-08-29 Horst Forschner Garment kit and method of assembly thereof

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA013864B1 (en) * 2008-08-29 2010-08-30 Лимонова, Анастасия Викторовна Method of enhancement antimicrobal activity of cephalosporin antibiotics

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4860900A (en) * 1986-08-19 1989-08-29 Horst Forschner Garment kit and method of assembly thereof

Also Published As

Publication number Publication date
CH522635A (en) 1972-05-15
SU495841A3 (en) 1975-12-15
FR1584569A (en) 1969-12-26
BR6910252D0 (en) 1973-02-08
IL32379A (en) 1973-10-25
DE1966203B2 (en) 1980-02-07
IL32379A0 (en) 1969-08-27
DE1966204A1 (en) 1971-10-21
GB1271018A (en) 1972-04-19
JPS5028440B1 (en) 1975-09-16
GB1271013A (en) 1972-04-19
GB1271015A (en) 1972-04-19
DE1967030A1 (en) 1976-07-29
DE1967030C3 (en) 1978-08-03
DE1932504A1 (en) 1970-01-15
BR6910250D0 (en) 1973-02-08
PL79142B1 (en) 1975-06-30
SU384232A3 (en) 1973-05-23
NL6909850A (en) 1969-12-30
CH515276A (en) 1971-11-15
GB1271017A (en) 1972-04-19
BR6910251D0 (en) 1973-02-08
DE1932498A1 (en) 1970-02-26
CH513206A (en) 1971-09-30
DE1932504B2 (en) 1977-03-17
JPS4934999B1 (en) 1974-09-19
NL142691B (en) 1974-07-15
AT293615B (en) 1971-10-25
ES368820A1 (en) 1971-05-16
NL142415B (en) 1974-06-17
ES395175A2 (en) 1974-01-16
AT293614B (en) 1971-10-25
DE1967030B2 (en) 1977-11-24
DE1966203C3 (en) 1980-10-09
NL6909849A (en) 1969-12-30
HU162644B (en) 1973-03-28
GB1271016A (en) 1972-04-19
BE735127A (en) 1969-12-29

Similar Documents

Publication Publication Date Title
DE1297610B (en) 2- (4-Benzylpiperazino) pyrimidine derivatives
DE1470082B2 (en) Process for the preparation of benzimidazoles substituted in the 2-position
DE1620450C3 (en) 1 - (2-Hydroxybenzyl) -2-piperazinomethylbenzimidazoles, processes for their preparation and pharmaceuticals containing them
DE1445186C3 (en) 3,3&#39;-di-2-imidazolin-2-yl-carbanilide
DE2718405A1 (en) NEW N-NECK CLAMP ON 1- (3-BENZOYLPROPYL) -4-PIPERIDYL NECK CLAMP ON -SULPHONIC ACID AMIDES AND METHOD FOR THE PRODUCTION THEREOF
DE1720019A1 (en) Pyrrylaminoketone derivatives and processes for their preparation
DE2429562A1 (en) BENZOXAZOLINONE DERIVATIVES
DE1966203A1 (en) New 2,3-Dioxo-4- (R &#39;, R &#34;) - aminomethyl-pyrrolidines and their production process
DE1283841B (en) Basically substituted ethers of ethanolamine
DE949232C (en) Process for the production of therapeutically valuable basic substituted acetic acid esters
DE940828C (en) Process for the preparation of esters of penicillin with phenols and thiophenols
DE1670378C (en) Process for the preparation of the salt from 4-n-butyl-3,5-dioxo-1,2-diphenylpyrazolidine and the beta-diethylamino-ethylamide of p-chlorophenoxyacetic acid
DE1670105A1 (en) Process for the preparation of benzofuryl (3) -alkylamines and their salts
AT219020B (en) Process for the preparation of new N-substituted amino-norcamphanderivaten and their acid addition salts and quaternary ammonium compounds
AT273959B (en) Process for the preparation of benzimidazole derivatives
AT278808B (en) Process for the preparation of new 4-acyl-3,4-dihydro-2 (1H) -quinoxalinone derivatives
AT282593B (en) PROCESS FOR THE PREPARATION OF NEW RACEMIC OR OPTICALLY ACTIVE (1-2&#39;-NITRILOPHENOXY) -2-HYDROXY-3-ISOPROPYLAMINOPROPANE AND ITS SALTS
DE1932498C (en) Process for the preparation of the threoisomers of 2- (alpha-carboxy-alpha-tritylamino-methyl) -5-aminomethyl-2,3-dihydro-U-thiazine ^ -carboxylic acid-gamma-lactams
DE1445722C (en) Carboxylic acid epiperazides
CH511842A (en) 3-amino-1 2 3 4-tetrahydrocarbazoles
DE2019719C3 (en) 1,3,4-Substituted 5-dimethylaminouracils and processes for their preparation
AT218518B (en) Process for the preparation of new alkyl-substituted, basic tetralone derivatives
DE1470205C (en) 5-Nitropyrrole derivatives and process for their preparation
AT228199B (en) Process for the preparation of a new imidazoline derivative and its salts
DE1470260C (en) 3,5 Dioxopyrazoiidine derivatives and a process for their preparation

Legal Events

Date Code Title Description
C3 Grant after two publication steps (3rd publication)
8339 Ceased/non-payment of the annual fee