NO762792L - - Google Patents

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Publication number
NO762792L
NO762792L NO762792A NO762792A NO762792L NO 762792 L NO762792 L NO 762792L NO 762792 A NO762792 A NO 762792A NO 762792 A NO762792 A NO 762792A NO 762792 L NO762792 L NO 762792L
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compound
carbon atoms
formula
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hydrogen
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NO762792A
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Norwegian (no)
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G Pifferi
M Pinza
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Isf Spa
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    • 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
    • C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—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 one double bond between ring members or between a ring member and a non-ring member 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
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Neurology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Detergent Compositions (AREA)
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Description

Foreliggende oppfinnelse vedrører en fremgangsmåte til fremstilling av pyrrolinderivater med farmakologisk aktivitet og med den generelle formel: The present invention relates to a method for the production of pyrroline derivatives with pharmacological activity and with the general formula:

hvor R-^og R2er like eller forskjellige og er hydrogen, alkyl med 1-3 karbonatomer, cykloalkyl med 5 eller 6 karbonatomer, where R-^ and R2 are the same or different and are hydrogen, alkyl with 1-3 carbon atoms, cycloalkyl with 5 or 6 carbon atoms,

eller R-^og R2danner sammen med det tilstøtende nitrogenatom en heterocyklisk ring som eventuelt inneholder et ytterligere heteroatom slik som oksygen og nitrogen, og hvor n er et helt tall fra 0-2 inklusive. or R-^ and R2 together with the adjacent nitrogen atom form a heterocyclic ring which possibly contains a further heteroatom such as oxygen and nitrogen, and where n is an integer from 0-2 inclusive.

Betegnelsen alkyl og cykloalkyl omfatter blantThe terms alkyl and cycloalkyl include among others

andre gruppene metyl, etyl, propyl, cyklopentyl og cykloheksyl. Substituentene R-^og R2kan sammen med det tilstøtende nitrogenatom danne en piperidin-, piperazin-, oksazolidin- og oksazin-ring. other groups methyl, ethyl, propyl, cyclopentyl and cyclohexyl. The substituents R 1 and R 2 can together with the adjacent nitrogen atom form a piperidine, piperazine, oxazolidine and oxazine ring.

Ifølge oppfinnelsen fremstilles pyrrolinforbindel-According to the invention, pyrroline compounds are produced

ser med formel I hvor n, R-^og R2har den ovenfor angitte betydning, ved dekarboalkoksylering av forbindelser med formel II for dannelse av 2,4-diketoforbindelsene med formel III som videre hydrogeneres for dannelse av 4-hydroksyforbindelser IV, hvilke deretter behandles med en egnet forbindelse som kan danne en lett fjernbar estergruppe i stilling 4, og suksessiv fjerning av syren med resulterende dannelse av dobbeltbinding, see with formula I where n, R-^ and R 2 have the above-mentioned meaning, by decarbo-alkylation of compounds of formula II to form the 2,4-diketo compounds of formula III which are further hydrogenated to form 4-hydroxy compounds IV, which are then treated with a suitable compound capable of forming an easily removable ester group in position 4, and successive removal of the acid with resulting formation of a double bond,

og endelig ammonolyse for fremstilling av sluttforbindelsen I. and final ammonolysis to produce the final compound I.

hvor R' er et alkylradikal med 1-3 karbonatomer, X er resten av en karboksylsyre eller sulfonsyre og hvor R^, R£og n har den ovenfor angitte betydning. where R' is an alkyl radical with 1-3 carbon atoms, X is the residue of a carboxylic acid or sulphonic acid and where R^, R£ and n have the meaning indicated above.

Dekarboalkoksyleringsreaksjonen a) av den nye forbindelse med formel II, som foreligger i equilibrium med sine keto/enol-former, forløper ved tilbakeløpskoking i et egnet oppløsningsmiddel i nærvær av vann, hvilket er nødvendig for å hydrolysere estergruppen i utgangsproduktet. The decarboalkylation reaction a) of the new compound of formula II, which exists in equilibrium with its keto/enol forms, proceeds by refluxing in a suitable solvent in the presence of water, which is necessary to hydrolyze the ester group in the starting product.

Forbindelsen som dannes og som har formel III underkastes hydrogenering i trinn b) med komplekse hydrider eller alternativt med hydrogen i nærvær av katalysatorer i egnede oppløsningsmidler. The compound which is formed and which has formula III is subjected to hydrogenation in step b) with complex hydrides or alternatively with hydrogen in the presence of catalysts in suitable solvents.

I en foretrukken utførelse av foreliggende fremgangsmåte behandles forbindelse III i et eteroppløsningsmiddel eller tetrahydrofuran med omtrent den støkiometriske mengde av natriumborhydrid. Forestringsreaksjonen c) av forbindelse IV forløper under vannfrie betingelser i et egnet organisk oppløs-ningsmiddel, slik som et halogenert hydrokarbon, ved hjelp av kloridet av en passende syre slik som metansulfonylklorid, p-toluensulfonylklorid, acetylklorid og benzoylklorid, ved en temperatur på fra -10°C til romtemperatur i nærvær av en egnet organisk base som kan binde syren som dannes. Mellomproduktet med formel V som dannes isoleres ikke og tilveiebringelsen av den dobbelte binding mellom karbonatomer 3-4 i trinn c'), oppnås ved oppvarming i nærvær av en egnet organisk base. Ammonolyse-reaksjonen i trinn d) av forbindelse VI forløper på kjent måte med ammoniakk eller et egnet amin med formel HNR^F^ hvor R-^og R2 har den ovenfor angitte betydning, med unntagelse av når R-^og R2 samtidig er hydrogen. In a preferred embodiment of the present process, compound III is treated in an ether solvent or tetrahydrofuran with approximately the stoichiometric amount of sodium borohydride. The esterification reaction c) of compound IV takes place under anhydrous conditions in a suitable organic solvent, such as a halogenated hydrocarbon, using the chloride of a suitable acid such as methanesulfonyl chloride, p-toluenesulfonyl chloride, acetyl chloride and benzoyl chloride, at a temperature of from - 10°C to room temperature in the presence of a suitable organic base which can bind the acid that is formed. The intermediate product of formula V which is formed is not isolated and the provision of the double bond between carbon atoms 3-4 in step c') is achieved by heating in the presence of a suitable organic base. The ammonolysis reaction in step d) of compound VI proceeds in a known manner with ammonia or a suitable amine of the formula HNR^F^ where R-^ and R2 have the above meaning, with the exception of when R-^ and R2 are simultaneously hydrogen .

Forbindelsene som fremstilles ifølge oppfinnelsen utviser aktivitet på CNS; og de ble testet i sammenligning med kontrollprøver og med det kjente produkt som har den nærmest beslektede struktur og lignende farmakologiske egenskaper, nemlig pyrazetan, dvs. 2-(pyrrolidin-2-on-l-yl)acetamid. Forbindelsene ble testet med hensyn til læring og hukommelse hvilket ble utført på følgende måte. The compounds produced according to the invention exhibit activity on the CNS; and they were tested in comparison with control samples and with the known product having the most closely related structure and similar pharmacological properties, namely pyrazetane, i.e. 2-(pyrrolidin-2-on-1-yl)acetamide. The compounds were tested with regard to learning and memory which was carried out in the following way.

a) Stolpeklatreforsøka) Pole climbing attempt

Det ble benyttet Wistar han-albinorotter som varMale albino Wistar rats were used

60 dager gamle ved forsøkenes begynnelse. Den benyttede metode er beskrevet av Cook L., Weidley E.F. (Ann.N.Y. Acad.Sci., 66, 740, 1957). Den forventede betingede respons (CR2) som er beskrevet av Maffii G. (J.Pharm.Pharmacol., 11, 129, 1959) ble også studert. Etter at rottene var anbragt i kondisjonerings-rommet ble følgende forsøksrekke benyttet: 15 sek. uten stimu-lering, 15 sek. med akustisk stimulus og 30 sek. med akustisk stimulus pluss elektrisk sjokk i poten (1,3 m A). Klatring av stolpen i løpet av de første 15 sek. uten stimulus er forventet betinget respons CR2, mens klatring av stolpen under akustisk stimulus er betinget respons CR-, . 60 days old at the start of the experiments. The method used is described by Cook L., Weidley E.F. (Ann. N. Y. Acad. Sci., 66, 740, 1957). The expected conditioned response (CR2) described by Maffii G. (J.Pharm.Pharmacol., 11, 129, 1959) was also studied. After the rats had been placed in the conditioning room, the following test sequence was used: 15 sec. without stimulation, 15 sec. with acoustic stimulus and 30 sec. with acoustic stimulus plus electric shock in the paw (1.3 m A). Climbing the pole during the first 15 sec. without stimulus the expected conditioned response CR2, while climbing the pole under acoustic stimulus is conditioned response CR-, .

Forsøksdyrene ble behandlet intraperitonealt eller oralt hver dag i 3 etterfølgende dager, en time før hver forsøksrekke.. Hver dag ble to forsøksrekker utført, nemlig kl. 9 og kl. 16. Lærehastigheten for både CR2og CR-^ble studert. The experimental animals were treated intraperitoneally or orally every day for 3 consecutive days, one hour before each experimental series. Each day, two experimental series were carried out, namely at 9 and at 16. The learning rate of both CR2 and CR-^ was studied.

b) Passiv unngåelse fulgt av maksimalt elektrosjokkb) Passive avoidance followed by maximum electroshock

Det ble benyttet sveitsiske han-albinomus som varMale Swiss albino mice were used

25 dager gamle. Den benyttede metode og apparat er i det vesentlige som beskrevet av Essman W.B. i Psychopharmacologia (Berl.) 9, 426, 1966. Passasje fra et lyst rom til et mørkt rom ble straffet med elektrisk sjokk i poten. (1,3 m A - 5 sek.). 25 days old. The method and apparatus used are essentially as described by Essman W.B. in Psychopharmacologia (Berl.) 9, 426, 1966. Passage from a light room to a dark room was punished with an electric shock to the paw. (1.3 m A - 5 sec.).

Umiddelbart etter forsøket ble et maksimalt elektro-konvulsivt sjokk (E.C.S.) 30 m A - 150 msek., 50 Hz, gitt til musene gjennom cornea-elektroder. Forbindelsene ble administrert intraperitonealt eller oralt 1 time før forsøket. Et nytt forsøk ble foretatt 24 timer etter E.C.S. Musene som ikke forflyttet seg fra det lyse rom til det mørke rom i løpet av 30 sek. ble betraktet som ikke-påvirket av den tilbakeholdende amnesiske effekt til E.C.S. Kontrolldyrene ble underkastet E.C.S, eller "shame E.C.S." Immediately after the experiment, a maximal electro-convulsive shock (E.C.S.) 30 mA - 150 msec., 50 Hz, was given to the mice through corneal electrodes. The compounds were administered intraperitoneally or orally 1 hour before the experiment. A second attempt was made 24 hours after the E.C.S. The mice that did not move from the light room to the dark room within 30 sec. was considered unaffected by the restraining amnesic effect of E.C.S. The control animals were subjected to E.C.S, or "sham E.C.S."

Følgende eksempler illustrerer oppfinnelsen. The following examples illustrate the invention.

Eksempel 1Example 1

2,( Å 3- pyrrolin- 2- on- l- yl) acetamid2,( Å 3-pyrrolin-2-on-1-yl)acetamide

Til en blanding ved 0°C av 648 g etyliminodiacetat i 3600 ml vannfritt metylenklorid og 572 ml trietylamin, ble det dråpevis og under omrøring tilsatt en oppløsning av 619 g 2-karbetoksyacetylklorid i 1100 ml metylenklorid mens det ble sørget for at reaksjonstemperaturen ikke overskred 10-15°C. To a mixture at 0°C of 648 g of ethyl iminodiacetate in 3600 ml of anhydrous methylene chloride and 572 ml of triethylamine, a solution of 619 g of 2-carbethoxyacetyl chloride in 1100 ml of methylene chloride was added dropwise and with stirring while ensuring that the reaction temperature did not exceed 10 -15°C.

Den resulterende blanding ble rystet i 2 timer ved romtemperatur, hensatt natten over, vasket med vann, tørket og inndampet i vakuum. N-(2-karbetoksyacetyl)-etyliminodiazetatet som ble oppnådd i form av en olje, ble oppløst i vannfri benzen og tilsatt ved romtemperatur til en oppløsning av 7 5,6 g natrium i 2700 ml absolutt etanol. Produktet ble oppvarmet under tilbake-løp og omrøring i 6 timer, avkjølt til romtemperatur, ekstrahert gjentatte ganger med vann og de oppsamlede vandige ekstrakter ble surgjort til pH 1 med konsentrert saltsyre, hvilket ga et bunnfall av 2-(3-karbetoksy-4-hydroksy-^ -pyrrolin-2-on-l-yl)-etylacetat,"som etter rensing ved krystallisering smeltet ved 175-179°C. The resulting mixture was shaken for 2 hours at room temperature, allowed to stand overnight, washed with water, dried and evaporated in vacuo. The N-(2-carbethoxyacetyl)-ethyliminodiacetate obtained as an oil was dissolved in anhydrous benzene and added at room temperature to a solution of 75.6 g of sodium in 2700 ml of absolute ethanol. The product was heated under reflux and stirring for 6 hours, cooled to room temperature, extracted repeatedly with water and the collected aqueous extracts were acidified to pH 1 with concentrated hydrochloric acid, yielding a precipitate of 2-(3-carbethoxy-4- hydroxy-^-pyrrolin-2-on-1-yl)-ethyl acetate," which after purification by crystallization melted at 175-179°C.

20 g 2-(3-karbetoksy-4-hydroksy-A -pyrrolin-2-on-l-yl)-etylacetat ble tilsatt i varm tilstand til 200 ml vannfri acetonitril og 1,8 ml vann. Blandingen ble oppvarmet under tilbakeløp i omtrent 20 min. og deretter avkjølt på et isbad og 20 g of 2-(3-carbethoxy-4-hydroxy-A-pyrrolin-2-on-1-yl)-ethyl acetate was added hot to 200 ml of anhydrous acetonitrile and 1.8 ml of water. The mixture was heated under reflux for about 20 min. and then cooled in an ice bath and

inndampet i vakuum, hvilket ga 2-(pyrrolidino-2,4-dion-l-yl)-etylacetat, smp. 87-91°C. evaporated in vacuo to give 2-(pyrrolidino-2,4-dion-1-yl)-ethyl acetate, m.p. 87-91°C.

Til 22,25 g 2-(pyrrolidin-2,4-dion-l-yl)-etylacetat i 44 5 ml vannfri dimetoksyetan avkjølt til 0°C, ble det tilsatt 1,52 g natriumborhydrid. Blandingen ble hensatt i 10 min. i et isbad og deretter 30 min. ved romtemperatur. Oppløsningen ble surgjort med 20 % saltsyre, filtrert i vakuum, inndampet i vakuum, opptatt i metylenklorid og tørket over magnesiumsulfat. Etter filtrering og inndampning i vakuum og suksessiv kromato-grafi ble forbindelsen 2-(4-hydroksypyrrolidin-2-on-l-yl)-etylacetat med kokepunkt på 180°C (under dekomponering) utskilt. To 22.25 g of 2-(pyrrolidin-2,4-dion-1-yl)-ethyl acetate in 44 5 ml of anhydrous dimethoxyethane cooled to 0°C, 1.52 g of sodium borohydride was added. The mixture was left for 10 min. in an ice bath and then 30 min. at room temperature. The solution was acidified with 20% hydrochloric acid, filtered in vacuo, evaporated in vacuo, taken up in methylene chloride and dried over magnesium sulfate. After filtration and evaporation in vacuo and successive chromatography, the compound 2-(4-hydroxypyrrolidin-2-on-1-yl)-ethyl acetate with a boiling point of 180°C (during decomposition) was separated.

En oppløsning av 15,82 g 2-(4-hydroksypyrrolidin-2-on-l-yl)-etylacetat i 306 ml vannfritt metylenklorid og 6,65 ml trietylamin ble behandlet ved -10°C med en oppløsning, som ble tilsatt dråpevis, av 6,65 ml metansulfonylklorid i 81 ml metylenklorid. Etter tilsetningen ble oppløsningen rystet i 1 time, hvoretter 6,65 ml trietylamin ble tilsatt, og det hele ble oppvarmet under tilbakeløp natten over og deretter ble ytterligere 3,82 ml trietylamin tilsatt og tilbakeløpskoking foretatt i 4 timer. Den oppnådde oppløsning ble deretter avkjølt, vasket med mettet natriumklorid, tørket, filtrert med trekull og deretter inndampet i vakuum. Resten ble opptatt i 500 ml metylalkohol og behandlet med gassformig ammoniakk ved 0°C i 3 timer. Etter henstand natten over, ble oppløsningsmidlet inndampet i vakuum og resten ga ved omkrystallisering 2-(A ■' 3-pyrrolin-2-on-l-yl)-acetamid, smp.- 149-151°C. A solution of 15.82 g of 2-(4-hydroxypyrrolidin-2-on-1-yl)-ethyl acetate in 306 ml of anhydrous methylene chloride and 6.65 ml of triethylamine was treated at -10°C with a solution, which was added dropwise , of 6.65 ml of methanesulfonyl chloride in 81 ml of methylene chloride. After the addition, the solution was shaken for 1 hour, after which 6.65 ml of triethylamine was added, and the whole was heated under reflux overnight and then another 3.82 ml of triethylamine was added and refluxed for 4 hours. The resulting solution was then cooled, washed with saturated sodium chloride, dried, filtered with charcoal and then evaporated in vacuo. The residue was taken up in 500 ml of methyl alcohol and treated with gaseous ammonia at 0°C for 3 hours. After standing overnight, the solvent was evaporated in vacuo and the residue yielded on recrystallization 2-(Δ 3-pyrrolin-2-on-1-yl)-acetamide, mp 149-151°C.

Eksempel 2Example 2

På samme måte som beskrevet ovenfor ble N-etyl-(A - pyrrolin-2-on-l-yl)-karboksyamid fremstilt, smp. 85-86°C. In the same way as described above, N-ethyl-(A-pyrrolin-2-on-1-yl)-carboxamide was prepared, m.p. 85-86°C.

Claims (1)

i Fremgangsmåte til fremstilling av pyrrolin-2-on-derivater med den generelle formel:i Process for the preparation of pyrrolin-2-one derivatives of the general formula: hvor R1 og R2 er like eller forskjellige og er hydrogen, alkyl med 1-3 karbonatomer, cykloalkyl med 5 eller 6 karbonatomer, eller R^ og R2 danner sammen med det tilstøtende nitrogenatom en heterocyklisk ring som eventuelt inneholder et ytterligere heteroatom slik som oksygen og nitrogen, og hvor n er et helt tall fra 0-2 inklusive, karakterisert ved at en forbindelse med den generelle formel: where R1 and R2 are the same or different and are hydrogen, alkyl with 1-3 carbon atoms, cycloalkyl with 5 or 6 carbon atoms, or R^ and R2 together with the adjacent nitrogen atom form a heterocyclic ring which optionally contains a further heteroatom such as oxygen and nitrogen, and where n is an integer from 0-2 inclusive, characterized in that a compound with the general formula: hvor R <1> er et alkylradikal med 1-3 karbonatomer og n har den ovenfor angitte betydning, oppvarmes i et egnet oppløsnings-middel inneholdende passende mengder vann og at den tilsvarende dekarboalkoksylatforbindelse som dermed oppnås og som har formelen: where R <1> is an alkyl radical with 1-3 carbon atoms and n has the above-mentioned meaning, is heated in a suitable solvent containing suitable amounts of water and that the corresponding decarboalkoxylate compound thus obtained and which has the formula: hvor R <1> og n har den ovenfor angitte betydning, hydrogeneres med komplekse hydrider i et egnet oppløsningsmiddel, den således oppnådde tilsvarende 4-hydroksyforbindelse med formelen: where R <1> and n has the above meaning, is hydrogenated with complex hydrides in a suitable solvent, the thus obtained corresponding 4-hydroxy compound with the formula: hvor R' og n har den ovenfor angitte betydning, behandles under passende betingelser med et egnet acyleringsmiddel i nærvær av en egnet organisk base, det oppnådde tilsvarende 4-acyloksy-derivat omdannes til den umettede A 3-forbindelse ved oppvarming i nærvær av en egnet organisk base, og ved at denne forbindelse behandles med ammoniakk eller et mono- eller di-substituert amin, HNR-^ F^ hvor R-^ og R2 har den ovenfor angitte betydning, med unntagelse av det tilfelle hvor både R-^ og R2 er hydrogen, for oppnåelse av den ønskede forbindelse.where R' and n have the meaning given above, is treated under suitable conditions with a suitable acylating agent in the presence of a suitable organic base, the corresponding 4-acyloxy derivative obtained is converted into the unsaturated A 3 compound by heating in the presence of a suitable organic base, and by this compound being treated with ammonia or a mono- or di-substituted amine, HNR-^ F^ where R-^ and R 2 have the meaning given above, with the exception of the case where both R-^ and R 2 is hydrogen, to obtain the desired compound.
NO762792A 1975-08-13 1976-08-11 NO762792L (en)

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Publication number Priority date Publication date Assignee Title
IT1075280B (en) 1977-02-11 1985-04-22 Isf Spa PROCEDURE FOR THE PREPARATION OF PYROLIDINE DERIVATIVES
IT1075564B (en) 1977-02-11 1985-04-22 Isf Spa PROCEDURE FOR THE PREPARATION OF PYROLIDINE DERIVATIVES
HU195773B (en) * 1985-09-24 1988-07-28 Lonza Ag Process for preparing alkyl esters of 4-alkoxy-3-pyrrolin-2-on-1-yl-acetic acid
IL80071A0 (en) * 1985-09-24 1986-12-31 Lonza Ag Pyrrolidine acetamide derivatives
CH668067A5 (en) * 1986-05-14 1988-11-30 Lonza Ag 4-ALKOXY-3-pyrroline-2-ON-1-YL-ESSIGSAEUREAMIDE, PRODUCTION AND USE THEREOF.
ITUA20161346A1 (en) * 2016-03-04 2017-09-04 Univ Degli Studi Di Parma USE OF 2-OXO-2H-PYRROL-1 (5H) DERIVATIVES -CARBOSSAMIDS AS ANTI-HIV AGENTS AND PROCESS FOR THEIR PRODUCTION
CN112876397B (en) * 2021-01-19 2022-03-18 江苏诚信药业有限公司 Preparation method of 2, 5-dihydro-2-oxo-1H-pyrrole-1-acetamide

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SE7608939L (en) 1977-02-14
CH602637A5 (en) 1978-07-31
DE2635854A1 (en) 1977-02-24
PT65459A (en) 1976-09-01
IN141326B (en) 1977-02-12
AU1679876A (en) 1978-02-16
PT65459B (en) 1978-07-03
JPS5223071A (en) 1977-02-21
FI762313A (en) 1977-02-14
BE845100A (en) 1977-02-11
DD126509A5 (en) 1977-07-20
YU196576A (en) 1982-05-31
NL7608947A (en) 1977-02-15
FR2320742A1 (en) 1977-03-11
AR211398Q (en) 1977-12-15
PT65460B (en) 1978-07-03
DK365276A (en) 1977-02-14
ES450644A1 (en) 1977-07-16

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