CH615423A5 - Process for the preparation of novel acid amides - Google Patents

Process for the preparation of novel acid amides Download PDF

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Publication number
CH615423A5
CH615423A5 CH498678A CH498678A CH615423A5 CH 615423 A5 CH615423 A5 CH 615423A5 CH 498678 A CH498678 A CH 498678A CH 498678 A CH498678 A CH 498678A CH 615423 A5 CH615423 A5 CH 615423A5
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dioxo
tetrahydro
dimethyl
formula
acid amides
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CH498678A
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German (de)
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Eberhard Dr Kutter
Volkhard Dr Austel
Joachim Dr Kaehling
Harald Dr Ziegler
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Thomae Gmbh Dr K
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C63/00—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings
    • C07C63/14—Monocyclic dicarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P9/06—Antiarrhythmics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • C07D217/24—Oxygen atoms

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  • Pharmacology & Pharmacy (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract

Novel acid amides of the accompanying formula I, in which R1 to R3, which are identical or different, denote hydrogen or alkyl having 1 to 3 carbon atoms, are prepared by desulphurising salts of appropriately substituted thioacetamides or acetamide acid methyl esters [sic] by means of oxidising agents. The novel compounds are distinguished by useful pharmacological properties, in particular by muscle relaxant, sedative, antiarrhythmic and anticonvulsive actions. <IMAGE>

Description

Die Erfindung betrifft ein Verfahren zur Herstellung neuer Säureamide der Formel I The invention relates to a process for the preparation of new acid amides of the formula I.

(I) (I)

- CO - N. - CO - N.

R. R.

R- R-

wonn bliss

Rj bis R3, die gleich oder verschieden sind, Wasserstoff oder Alkyl mit 1 bis 3 Kohlenstoffatomen bedeuten. Rj to R3, which are the same or different, denote hydrogen or alkyl having 1 to 3 carbon atoms.

Die ähnlichste vorbekannte Verbindung, nämlich a-Homo-phthalimidopropionamid, wird in CA. 64 (1966) 19480g beschrieben. Diese Verbindung weist eine antidepressive Wirkung auf. Demgegenüber zeichnen sich die erfindungsgemäss erhältlichen neuen Verbindungen, die sich von der in der obengenannten Literaturstelle beschriebenen Verbindung durch die beiden Methylgruppen in 4-Stellung unterscheiden, durch muskelrelaxierende, sedierende, antiarrhythmische und antikonvulsive Wirkung aus. The most similar previously known compound, namely a-homophthalimidopropionamide, is described in CA. 64 (1966) 19480g. This compound has an antidepressant effect. In contrast, the novel compounds obtainable according to the invention, which differ from the compound described in the abovementioned reference by the two methyl groups in the 4-position, are distinguished by muscle-relaxing, sedating, antiarrhythmic and anticonvulsant activity.

Die Verbindungen der Formel I werden erfindungsgemäss hergestellt, indem man eine Verbindung der Formel II The compounds of formula I are prepared according to the invention by using a compound of formula II

(II) (II)

„0 "0

worin wherein

20 R4 Wasserstoff oder einen Alkyl-, Aralkyl- oder Arylrest und 20 R4 is hydrogen or an alkyl, aralkyl or aryl radical and

X ein Säureanion oder, falls eines der Symbole R2 bis R4 ein Wasserstoffatom darstellt, den Rest einer Base bedeuten, entschwefelt, indem man die Verbindung der For-25 mei II mit einem Oxydationsmittel, z. B. Wasserstoffperoxyd, Kaliumpermanganat oder Jod, in einem Lösungsmittel, wie Eisessig, behandelt. X is an acid anion or, if one of the symbols R2 to R4 represents a hydrogen atom, the rest of a base, desulfurized by combining the compound of formula 25 with II with an oxidizing agent, e.g. As hydrogen peroxide, potassium permanganate or iodine, treated in a solvent such as glacial acetic acid.

Die als Ausgangsmaterialien dienenden Verbindungen der Formel II sind grösstenteils literaturbekannt oder lassen sich 30 nach literaturbekannten Verfahren (siehe Beispiele) herstellen. Most of the compounds of formula II which serve as starting materials are known from the literature or can be prepared by processes known from the literature (see examples).

Wie bereits erwähnt, weisen die neuen Verbindungen der Formel I wertvolle pharmakologische Eigenschaften bei langanhaltender Wirksamkeit auf. Sie zeichnen sich insbesondere 35 durch muskelrelaxierende, sedierende, antiarrhythmische und antikonvulsive Wirkungen aus. As already mentioned, the new compounds of the formula I have valuable pharmacological properties with long-lasting activity. They are characterized in particular by muscle relaxant, sedative, antiarrhythmic and anticonvulsant effects.

Auf ihre biologische Wirkung wurden folgende Verbindungen untersucht: The following compounds were examined for their biological effect:

40 A = 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-iso-chinolyl-(2)l-acetamid, B = 2-[ 1,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-iso- 40 A = 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-iso-quinolyl- (2) l-acetamide, B = 2- [1,2,3, 4-tetrahydro-4,4-dimethyl-l, 3-dioxo-iso-

chinolyl-(2)]-essigsäure-methylamid, C = 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-iso-45 chinolyl-(2)]-propionamid, quinolyl- (2)] - acetic acid-methylamide, C = 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-iso-45 quinolyl- (2)] - propionamide,

D = 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-iso- D = 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-iso-

chinolyl-(2)]-essigsäure-äthylamid, E = 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-iso-chinolyl-(2)]-essigsäure-propylamid, 50 F = 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-iso-chinolyl-(2)]-essigsäure-isopropylamid, und G = 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-iso-chinolyl-(2)]-essigsäure-dimethylamid. quinolyl- (2)] - acetic acid-ethylamide, E = 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-iso-quinolyl- (2)] - acetic acid-propylamide , 50 F = 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-iso-quinolyl- (2)] - acetic acid-isopropylamide, and G = 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-1,3-dioxo-iso-quinolyl- (2)] - acetic acid-dimethylamide.

55 1. Muskelrelaxierende und sedierende Wirkung bei Mäusen Diese wurde nach der Methode von Young and Lewis [Science 105, (1947) 368] an weiblichen NMRI-Mäusen eigener Zucht mit einem Körpergewicht zwischen 20 und 26 g mittels sich langsam drehender, um 30° gegen die Vertikale 60 geneigter Drahtzylinder (Länge: 43 cm; Durchmesser: 22 cm; Maschenweite des Drahtgeflechtes: 0,6 cm) untersucht. Nach peroraler Applikation der zu prüfenden Substanz in 1 <% iger Tylosesuspension an Gruppen von 10 Mäusen/Dosis wurde deren Haltefähigkeit in den langsam rotierenden Zylindern es (2 Drehungen/Minute) gegenüber einer Kontrollgruppe geprüft. Es wurde die Dosis (ED50) graphisch ermittelt, bei welcher nach den verschiedenen Zeiten 50% der Tiere herausgefallen waren: 55 1. Muscle relaxant and sedative effect in mice This was determined by the method of Young and Lewis [Science 105, (1947) 368] on female NMRI mice of their own breeding with a body weight between 20 and 26 g by means of slowly rotating by 30 ° 60 inclined wire cylinders against the vertical (length: 43 cm; diameter: 22 cm; mesh size of the wire mesh: 0.6 cm) were examined. After oral administration of the substance to be tested in 1% tylose suspension to groups of 10 mice / dose, its holding capacity in the slowly rotating cylinders (2 rotations / minute) was checked against a control group. The dose (ED50) at which 50% of the animals had dropped out after the different times was determined graphically:

615 423 615 423

Substanz substance

EDjo mg/kg p.o. 30-60 120-150 EDjo mg / kg p.o. 30-60 120-150

210-240 210-240

270-300 Minuten 270-300 minutes

A A

40 40

34 34

52 52

32 32

B B

48 48

71 71

100 100

— -

D D

70 70

110 110

— -

— -

E E

95 95

140 140

— -

— -

F F

75 75

110 110

— -

— -

G G

34 34

67 67

71 71

100 100

2. Antikonvulsive Wirkung bei Mäusen Die antikonvulsive Wirkung wurde als Schutzwirkung gegen den maximalen Elektroschock-Krampf bei männlichen NMRI-Mäusen eigener Zucht mit einem Körpergewicht zwischen 20 und 26 g in Anlehnung an die Methode von Swinyard, Brown and Goodman [J. Pharmacol. exp. Therap. 106 (1952) 319] untersucht. Hierbei wurden die Tiere einem Wechselstrom von 50 Hz und 50 mA bei einer Reizdauer von 0,2 Sekunden ausgesetzt, wobei das Auftreten des tonischen Streckkrampfes als positiv gewertet wurde. Nach peroraler Applikation der zu prüfenden Substanzen in 1 %iger Tylose-suspension wurde die Dosis (EDS0) graphisch ermittelt, bei welcher nach verschiedenen Zeiten 50% der Tiere gegen die tonische Extensorkomponente der Hinterextremitäten beim Krampf geschützt waren: 2. Anticonvulsive effect in mice The anticonvulsive effect was used as a protective action against the maximum electroshock spasm in male NMRI mice of our own breed with a body weight between 20 and 26 g based on the method of Swinyard, Brown and Goodman [J. Pharmacol. exp. Therapist 106 (1952) 319]. The animals were exposed to an alternating current of 50 Hz and 50 mA with a stimulus duration of 0.2 seconds, the occurrence of the tonic stretching spasm being rated as positive. After oral administration of the substances to be tested in a 1% tylose suspension, the dose (EDS0) was determined graphically, at which 50% of the animals were protected against the tonic extensor component of the hind limbs during the cramp after various times:

Substanz substance

EDsomg/kg p.o. 30 EDsomg / kg p.o. 30th

150 150

300 Minuten 300 minutes

A B C D F G A B C D F G

21 21st

22 36 31 26 25 22 36 31 26 25

21 25 32 69 42 52 21 25 32 69 42 52

23 28 39 23 28 39

io io

20 20th

30 30th

35 35

3. Antiarrhythmische Wirkung an Meerschweinchen Die antiarrhythmische Wirkung wurde als Antagonismus gegenüber digitalisbedingter Arrhythmien bestimmt: 3. Antiarrhythmic effect on guinea pigs The antiarrhythmic effect was determined as an antagonism against digitalis-related arrhythmias:

In die obere Hohlvene von 11 narkotisierten Meerschweinchen (1,5 g/kg i. p. Urethan) mit einem Gewicht von 335 bis 385 g wurde ein Katheter zur Infusion von Digoxin und Injektion der Substanz A eingebunden. Digoxin wurde mit 20 y/Min. so lange intravenös infundiert, bis ventrikuläre Arrhythmien auftraten. Nach Beendigung der Infusion wurde bei 5 Tieren 40 mg/kg Substanz A (2%ig in 40% Polydiol) innerhalb 1 bis 2 Minuten intravenös gegeben. A catheter for the infusion of digoxin and injection of substance A was integrated into the upper vena cava of 11 anesthetized guinea pigs (1.5 g / kg i.p. urethane) weighing 335 to 385 g. Digoxin was at 20 y / min. infused intravenously until ventricular arrhythmias occurred. After the infusion had ended, 40 mg / kg of substance A (2% in 40% polydiol) were administered intravenously to 5 animals within 1 to 2 minutes.

Ergebnis Result

Die glykosidbedingten Arrhythmien dauerten bei der Kontrollgruppe (6 Tiere) nach Beendigung der Digoxin-In-fusion noch weitere 13 bis 20 Minuten, während bei der Substanzgruppe (5 Tiere) diese sofort nach Injektion der Substanz A beseitigt waren. In the control group (6 animals), the glycoside-related arrhythmias continued for a further 13 to 20 minutes after the digoxin-in-fusion had ended, while in the substance group (5 animals) these were eliminated immediately after the injection of substance A.

Die Verbindungen der Formel I weisen überdies eine geringe akute Toxizität auf, so beträgt beispielsweise die LDS0 für die Verbindung A an der Maus 1136 mg/kg p. o. (Beobachtungszeit: 14 Tage). The compounds of the formula I also have a low acute toxicity, for example the LDS0 for the compound A on the mouse is 1136 mg / kg p. o. (observation period: 14 days).

Zur pharmazeutischen Anwendung können die Verbindungen der Formel I in die üblichen pharmazeutischen Zubereitungen eingearbeitet werden. Die Einzeldosis beträgt hierbei 50 bis 300 mg, vorzugsweise jedoch 50 bis 200 mg. For pharmaceutical use, the compounds of the formula I can be incorporated into the customary pharmaceutical preparations. The single dose is 50 to 300 mg, but preferably 50 to 200 mg.

Die nachfolgenden Beispiele sollen die Erfindung näher erläutern: The following examples are intended to explain the invention in more detail:

Beispiel 1 example 1

a) 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-iso- a) 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-iso-

chinolyl-(2)]-thioacetamid In eine Lösung von 10 g 2-[l,2,3,4-Tetrahydro-4,4-di-methyl-l,3-dioxo-isochinolyl-(2)]-acetonitril in 12 ml Pyridin und 5 ml Triäthylamin wird unter Rühren während einer Stunde Schwefelwasserstoff eingeleitet, dann Wasser zugesetzt, das ausgefallene Produkt abgesaugt und aus Methanol und dann Essigester umkristallisiert. quinolyl- (2)] - thioacetamide In a solution of 10 g of 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-isoquinolyl- (2)] - acetonitrile in 12 ml of pyridine and 5 ml of triethylamine are introduced with stirring for one hour, hydrogen sulfide, then water is added, the precipitated product is filtered off and recrystallized from methanol and then ethyl acetate.

Schmelzpunkt: 206 bis 208° C. Melting point: 206 to 208 ° C.

b) 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-iso- b) 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-iso-

chinolyl-(2)]-acetamid 0,5 g 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-iso-chinolyl-(2)]-thioacetamid, gelöst in Eisessig, werden mit 0,5 ml 30%igem Wasserstoffperoxyd versetzt. Nach Stehen über Nacht wird das Lösungsmittel entfernt und der Rückstand aus Isopropanol umkristallisiert. quinolyl- (2)] - acetamide 0.5 g 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-iso-quinolyl- (2)] - thioacetamide, dissolved in Glacial acetic acid is mixed with 0.5 ml of 30% hydrogen peroxide. After standing overnight, the solvent is removed and the residue is recrystallized from isopropanol.

Schmelzpunkt: 182 bis 184° C. Melting point: 182 to 184 ° C.

Beispiel 2 Example 2

a) 2-[ 1,2,3,4-Tetrahydro-4,4-dimethyl-1,3-dioxo-iso-chinolyI-(2)]-acetimidsäure-thiomethylester-hydrojodid 1 g 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-isochi-nolyl-(2)]-thioacetamid wird mit 10 ml Aceton und 1 ml Methyljodid 3 Stunden unter Rückfluss erhitzt, anschliessend 100 ml Äther zugesetzt und nach Eiskühlung die ausgefallenen Kristalle abgesaugt. a) 2- [1,2,3,4-tetrahydro-4,4-dimethyl-1,3-dioxo-iso-quinolyI- (2)] - acetimidic acid thiomethyl ester hydroiodide 1 g of 2- [l, 2, 3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-isochinolyl- (2)] - thioacetamide is heated under reflux with 10 ml of acetone and 1 ml of methyl iodide for 3 hours, then 100 ml of ether are added and then Ice cooling the precipitated crystals are suctioned off.

Schmelzpunkt: ab 185° C (Zers.). Melting point: from 185 ° C (decomp.).

b) 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-iso-chinolyl-(2)]-acetamid Hergestellt aus 0,5 g 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-isochinolyl-(2)]-acetimidsäure-thiomethylester-hydrojodid und 30%igem Wasserstoffoxyd in Eisessig analog 40 Beispiel lb. b) 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-iso-quinolyl- (2)] - acetamide Made from 0.5 g of 2- [l, 2, 3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-isoquinolyl- (2)] - acetimidic acid thiomethyl ester hydroiodide and 30% hydrogen oxide in glacial acetic acid analogous to 40 Example lb.

Schmelzpunkt: 182 bis 184° C. Melting point: 182 to 184 ° C.

Analog den Beispielen 1 und 2 wurden folgende Verbindungen hergestellt: The following compounds were prepared analogously to Examples 1 and 2:

2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-isochinolyl-45 (2)]-essigsäure-methylamid 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-isoquinolyl-45 (2)] acetic acid methyl amide

Schmelzpunkt: 182 bis 184° C 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-isochinolyl-(2) ]-essigsäure-propionamid Schmelzpunkt: 184 bis 186° C 50 2-[ 1,2,3,4-Tetrahydro-4,4-dimethyl- 1,3-dioxo-isochinolyl-(2)]-essigsäure- äthylamid Schmelzpunkt: 143 bis 145° C 2-[l ,2,3,4-Tetrahydro-4,4-dimethyl-1,3-dioxo-isochinolyl-(2)]-essigsäure-propylamid 55 Schmelzpunkt: 116 bis 118° C Melting point: 182 to 184 ° C 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-isoquinolyl- (2)] -acetic acid propionamide Melting point: 184 to 186 ° C 50 2- [1,2,3,4-tetrahydro-4,4-dimethyl-1,3-dioxo-isoquinolyl- (2)] - acetic acid-ethylamide Melting point: 143 to 145 ° C 2- [1,2,3 , 4-tetrahydro-4,4-dimethyl-1,3-dioxo-isoquinolyl- (2)] - acetic acid propylamide 55 Melting point: 116 to 118 ° C

2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-isochinolyl-(2)]-essigsäure-isopropylamid Schmelzpunkt: 125 bis 128° C 2-[l,2,3,4-Tetrahydro-4,4-dimethyl-l,3-dioxo-isochinolyl-60 (2)]-essigsäure-dimethylamid Schmelzpunkt: 183 bis 185° C 2- [l, 2,3,4-tetrahydro-4,4-dimethyl-l, 3-dioxo-isoquinolyl- (2)] - acetic acid-isopropylamide melting point: 125 to 128 ° C 2- [l, 2,3 , 4-tetrahydro-4,4-dimethyl-l, 3-dioxo-isoquinolyl-60 (2)] - acetic acid-dimethylamide melting point: 183 to 185 ° C

Claims (3)

615 423 615 423 2. Verfahren nach Patentanspruch 1, dadurch gekennzeichnet, dass man als Oxydationsmittel Wasserstoffperoxyd, Kaliumpermanganat oder Jod verwendet. 2. The method according to claim 1, characterized in that hydrogen peroxide, potassium permanganate or iodine is used as the oxidizing agent. 2 2nd PATENTANSPRÜCHE 1. Verfahren zur Herstellung neuer Säureamide der Formel I „„ PATENT CLAIMS 1. Process for the preparation of new acid amides of the formula I "" en en .o (I) .o (I) worin wherein Rj bis R3, die gleich oder verschieden sind, Wasserstoff oder Alkyl mit 1 bis 3 Kohlenstoffatomen bedeuten, dadurch gekennzeichnet, dass man eine Verbindung der Formel II Rj to R3, which are the same or different, denote hydrogen or alkyl having 1 to 3 carbon atoms, characterized in that a compound of formula II (II) (II) /SRH / SRH CH ' V®/R2 CH 'V® / R2 X X \ \ R. R. worin wherein R4 Wasserstoff oder einen Alkyl-, Aralkyl- oder Aryl-rest und R4 is hydrogen or an alkyl, aralkyl or aryl radical and X ein Säureanion oder, falls eines der Symbole R2 bis R4 ein Wasserstoffatom darstellt, den Rest einer Base bedeuten, entschwefelt, indem man die Verbindung der Formel II in einem Lösungsmittel mit einem Oxydationsmittel behandelt. X is an acid anion or, if one of the symbols R2 to R4 represents a hydrogen atom, the rest of a base, is desulfurized by treating the compound of the formula II in a solvent with an oxidizing agent. 3. Verfahren nach Patentanspruch 1, dadurch gekennzeichnet, dass man die Entschwefelung bei einer Temperatur von 0 bis 160° C durchführt. 3. The method according to claim 1, characterized in that one carries out the desulfurization at a temperature of 0 to 160 ° C.
CH498678A 1972-08-01 1978-05-08 Process for the preparation of novel acid amides CH615423A5 (en)

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CH498578A CH611887A5 (en) 1972-08-01 1978-05-07 Process for the preparation of novel acid amides
CH498678A CH615423A5 (en) 1972-08-01 1978-05-08 Process for the preparation of novel acid amides
CH638878A CH612184A5 (en) 1972-08-01 1978-06-12 Process for the preparation of novel acid amides
CH639078A CH611280A5 (en) 1972-08-01 1978-06-12 Process for the preparation of novel acid amides
CH638978A CH611888A5 (en) 1972-08-01 1978-06-12 Process for the preparation of novel acid amides

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CH638978A CH611888A5 (en) 1972-08-01 1978-06-12 Process for the preparation of novel acid amides

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FR (1) FR2194435A1 (en)
GB (1) GB1450793A (en)
NL (1) NL7310562A (en)

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Publication number Publication date
CH611887A5 (en) 1979-06-29
ES422932A1 (en) 1976-06-16
ES422933A1 (en) 1976-06-16
JPS558973B2 (en) 1980-03-07
ES422929A1 (en) 1976-06-16
ATA673773A (en) 1975-07-15
CH612184A5 (en) 1979-07-13
DK137008C (en) 1978-05-22
DK137008B (en) 1978-01-02
AU476552B2 (en) 1976-09-30
GB1450793A (en) 1976-09-29
FI52218C (en) 1977-07-11
JPS4980080A (en) 1974-08-02
FI52218B (en) 1977-03-31
CH615918A5 (en) 1980-02-29
AT329059B (en) 1976-04-26
AU5873573A (en) 1975-02-06
ATA225975A (en) 1975-07-15
ES422931A1 (en) 1976-06-16
ES422930A1 (en) 1976-06-16
AT329060B (en) 1976-04-26
CH611888A5 (en) 1979-06-29
FR2194435A1 (en) 1974-03-01
CH611280A5 (en) 1979-05-31
NL7310562A (en) 1974-02-05
ES417443A1 (en) 1976-03-16
DE2237770A1 (en) 1974-02-14
BE803086A (en) 1974-01-31

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