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DE2157040A1 - 4-amino-3,5-dihalophenylethanolamines prepn - by hydrolysis of 5-(4-amino-3,5-dihalo-phenyl)-2-oxazolidones - Google Patents

4-amino-3,5-dihalophenylethanolamines prepn - by hydrolysis of 5-(4-amino-3,5-dihalo-phenyl)-2-oxazolidones

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Publication number
DE2157040A1
DE2157040A1 DE2157040A DE2157040A DE2157040A1 DE 2157040 A1 DE2157040 A1 DE 2157040A1 DE 2157040 A DE2157040 A DE 2157040A DE 2157040 A DE2157040 A DE 2157040A DE 2157040 A1 DE2157040 A1 DE 2157040A1
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Prior art keywords
amino
formula
solvent
oxazolidones
oxazolidone
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Pending
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DE2157040A
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German (de)
Inventor
Johannes Dr Dipl Chem Keck
Axel Dipl Chem Dr Prox
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.)
Boehringer Ingelheim Pharma GmbH and Co KG
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Dr Karl Thomae GmbH
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Priority to DE2157040A priority Critical patent/DE2157040A1/en
Priority to JP10453671A priority patent/JPS5512893B2/ja
Priority to AT943572A priority patent/AT320618B/en
Priority to AT1038373A priority patent/AT320642B/en
Priority to CH1654972A priority patent/CH574903A5/xx
Priority to YU2815/72A priority patent/YU35870B/en
Priority to SU1847357A priority patent/SU468398A3/en
Priority to DD174171*A priority patent/DD108297A5/xx
Priority to ES408615A priority patent/ES408615A1/en
Priority to HUTO936A priority patent/HU166034B/hu
Priority to DD166875A priority patent/DD103640A5/xx
Priority to HUTO893A priority patent/HU164697B/hu
Priority to BG021865A priority patent/BG20337A3/en
Priority to RO7272820A priority patent/RO68219A/en
Priority to CS7736A priority patent/CS170454B2/cs
Priority to CA156,600A priority patent/CA987685A/en
Priority to PL1972158883A priority patent/PL79757B1/pl
Publication of DE2157040A1 publication Critical patent/DE2157040A1/en
Priority to DK086574AA priority patent/DK150851B/en
Priority to SE7505550A priority patent/SE405854B/en
Priority to JP12337176A priority patent/JPS5293767A/en
Priority to FI792528A priority patent/FI792528A/en
Priority to YU2525/79A priority patent/YU40763B/en
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings 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
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Cpds. of formula (I): (where Hal is Cl or Br and R is H or 1-5C alkyl) and their physiologically tolerable acid addn. salts, which have pharmacological (e.g. analgesic or broncholytic) props., are prepd. by subjecting novel oxazolidones of formula (II): (obtd. by chlorination or bromination of corresp. cpds. lacking Hal) to acidic or alkaline hydrolysis and opt. converting the product into an acid addn. salt with an organic or inorganic acid.

Description

Neues Verfahren zur Herstellung von 4-Amino-3,5-dihalogenphenyl-äthanolantinen im Belgischen Patent 704.213 werden mehrere Verfahren zur 11erstellung von )I-Amino-3,5-dihalogen-phenyl-äthanolaminen der allgemeinen Formel I, in der Hal ein Chlor- oder Bromatom und R ein Wasserstoffatom oder einen Alkylrest mit 1 - 5 Kohlenstoffatomen, vorzugsweise jedoch die Methyl-, Xthyl-, Propyl-, tert.New process for the preparation of 4-amino-3,5-dihalogenophenylethanolamines in Belgian patent 704.213 describe several processes for the preparation of) I-amino-3,5-dihalogenophenylethanolamines of the general formula I, in which Hal is a chlorine or bromine atom and R is a hydrogen atom or an alkyl radical with 1-5 carbon atoms, but preferably the methyl, ethyl, propyl, tert.

Butyl- oder iso-Pentylgruppe, bedeuten, beschrieben.Butyl or iso-pentyl group, are described.

Die Verbindungen der obigen allgemeinen Formel I besitzen wertvolle pharmakologische Eigenschaften; die Verbindungen, in denen R ein Wasserstoffatom,die Methyl- oder Xthylgruppe darstellt, insbesondere analgetische, und Verbindungen, in denen R die tert. Butyl- oder iso- Pentylgruppe darstellt, broncholytische Eigenschaften.The compounds of the above general formula I have valuable pharmacological properties; the compounds in which R is a hydrogen atom, the Represents methyl or ethyl group, especially analgesic, and compounds, in which R is the tert. Represents butyl or iso-pentyl group, broncholytic properties.

Nach den in der obengenannten Patentschrift beschriebenen Verfahren lassen sich diese Verbindungen der obigen allgemeinen Formel 1 lediglich in einer maximalen Ausbeute von ca. 65 der Theorie herstellen. Überraschenderweise wurde nun festgestellt, daß sich diese Verbindungen ausgehend von neuen Verbindungen der allgemeinen Formel II, Hal und R wie eingangs definiert sind, oder von deren Säureadditionssalzen mittels Hydrolyse in Ausbeuten bis zu ca. 90 % der Theorie herstellen lassen.According to the processes described in the above-mentioned patent, these compounds of the above general formula 1 can only be prepared in a maximum yield of about 65% of theory. Surprisingly, it has now been found that these compounds, starting from new compounds of the general formula II, Hal and R are as defined at the outset, or can be prepared from their acid addition salts by hydrolysis in yields of up to about 90% of theory.

Gegenstand der vorliegenden Anmeldung ist somit ein verbessertes Verfahren zur Herstellung der Verbindungen der obigen allgemeinen Formel I sowie die neuen Zwischenprodukte der allgemeinen Formel II.The present application therefore relates to an improved process for the preparation of the compounds of the above general formula I and the new ones Intermediate products of the general formula II.

Die Hydrolyse einer Verbindung der allgemeinen Formel II bzw.The hydrolysis of a compound of the general formula II or

deren Säureadditionssalzen kann sowohl sauer als auch alkalisch erfolgen, sie wird jedoch vorzugsweise in Gegenwart einer Base, zum Beispiel einem Alkalihydroxid wie-Natriumhydroxid oder Kaliumhydroxid, zweckmäßigerweise in einem Lösungsmittel wie thylenglykolmonomethYläther oder in einem Alkohol wie Isopropanol und unter Zusatz von etwas Wasser, bei erhöhten Temperaturen, beispielsweise bei Temperaturen zwischen 80 und 100 0C oder bei der Siedetemperatur des verwendeten Lösungsmittels, durchgeführt.their acid addition salts can be acidic or alkaline, however, it is preferably used in the presence of a base such as an alkali hydroxide such as sodium hydroxide or potassium hydroxide, conveniently in a solvent such as ethylene glycol monomethyl ether or in an alcohol such as isopropanol and below Addition of some water at elevated temperatures, for example at temperatures between 80 and 100 0C or at the boiling point of the solvent used, carried out.

Die neuen Zwischenprodukte der allgemeinen Formel II erhält man durch Halogenierung eines Oxazolidons der allgemeinen Formel III, in der R wie eingangs definiert ist, oder deren Säureadditionssalzen in einem Lösungsmittel mit mindestens 2 Mol Brom oder Chlor.The new intermediates of the general formula II are obtained by halogenation of an oxazolidone of the general formula III, in which R is as defined at the outset, or its acid addition salts in a solvent with at least 2 moles of bromine or chlorine.

Die Halogenierung wird in einem Lösungsmittel wie 50-100 einer Essigsäure oder in einem halogenierten Kohlenwasserstoff wie Chloroform oder in einem Alkohol wie äthanol und vorzugsweise bei Temperaturen zwischen 0 und 50°C durchgefilhrt.The halogenation is carried out in a solvent such as 50-100 of an acetic acid or in a halogenated hydrocarbon such as chloroform or in an alcohol like ethanol and preferably carried out at temperatures between 0 and 50 ° C.

Die als Ausgangs stoffe verwendeten Verbindungen der allgemeinen Formel III können beispielsweise aus den entsprechenden 4-Nitro phenyl-äthanolaminen durch Umsetzung mit Phosgen und anschließende Reduktion der Nitrogruppe erhalten werden.The compounds of the general formula used as starting materials III can, for example, from the corresponding 4-nitro phenylethanolamines Reaction with phosgene and subsequent reduction of the nitro group can be obtained.

Die erhaltenen Verbindungen der allgemeinen Formel I können mit beliebigen anorganischen oder organischen Säuren in ihre physiologisch verträglichen Säureadditionssalze übergeführt werden, beispielsweise durch Umsetzung mit einer alkoholischen Lösung der betreffenden Säuren. Als Säuren haben sich beispielsweise Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Phosphorsäure, Milchsäure, Zitronensäure, Weinsäure, Maleinsäure oder Fumarsäure als geeignet erwiesen. Die erhaltenen Salze sind.wasserlöslich, außerdem lassen sich Salze mit einem oder zwei Aquivalenten der betreffenden Säure herstellen.The compounds of general formula I obtained can with any inorganic or organic acids into their physiologically compatible acid addition salts be transferred, for example by reaction with an alcoholic solution of the acids in question. As acids, for example, hydrochloric acid, hydrobromic acid, Sulfuric acid, phosphoric acid, lactic acid, citric acid, tartaric acid, maleic acid or fumaric acid proved to be suitable. The salts obtained are soluble in water, in addition, salts with one or two equivalents of the acid in question can be used produce.

Die nachfolgenden Beispiele sollen die Erfindung näher erläutern: 1.) Herstellung der neuen Oxazolidone: a) 5-(11-Amino-3'5-dibrom-phenyl)-3-tert.-butyl-oxazolidon-(2) 2,8 g 5-(4-Amino-phenyl)-3-tert.-butyl-oxazolidon-(2) (Schmelzpunkt: 102-1040C) werden in 50 ccm Fisessig und 2 cem Wasser gelöst und unter Rühren innerhalb weniger Minuten mit einer Lösung von 3,9 g Brom in 1o ccm Eisessig tropfenweise versetzt. Nach 15 Minuten wird das Reaktionsgemisch mit 250 ccm Wasser verdünnt, zweimal mit Chloroform extrahiert, die organische Phase mit Wasser ausgeschüttelt, mit Natriumsulfat getrocknet und eingeengt. Den Rückstand löst man in wenig Essigester und bringt das 5-(11-Amino-3,5-dibrom-phenyl)-3-tert .-butyl-oxazolidon-(2) durch Zusatz von Petroläther zur Kristallisation.The following examples are intended to explain the invention in more detail: 1.) Production of the new oxazolidones: a) 5- (11-Amino-3'5-dibromophenyl) -3-tert-butyl-oxazolidone- (2) 2.8 g of 5- (4-aminophenyl) -3-tert-butyl-oxazolidone- (2) (melting point: 102-1040C) are dissolved in 50 cc of fish vinegar and 2 cem of water and stirred for less Minutes with a solution of 3.9 g of bromine in 10 cc of glacial acetic acid added dropwise. After 15 minutes, the reaction mixture is diluted with 250 ccm of water, twice with Chloroform extracted, the organic phase extracted with water, with sodium sulfate dried and concentrated. The residue is dissolved in a little ethyl acetate and brought 5- (11-Amino-3,5-dibromophenyl) -3-tert-butyl-oxazolidone- (2) by adding Petroleum ether for crystallization.

Schmelzpunkt: 118,5-1200C. Melting point: 118.5-1200C.

Auf die gleiche Weise wurden durch Chlorierung oder Bromierung folgende weitere neuen Verbindungen erhalten: b) 5-(4-Amino-3,5-dichlor-phenyl)-3-tert.-butyl-oxazolidon-(2) Hergestellt durch Chlorierung von 5-(4-Amino-phenyl)-3-tert.-butyl-oxazolidon-(2). In the same way, chlorination or bromination became the following received further new compounds: b) 5- (4-Amino-3,5-dichloro-phenyl) -3-tert-butyl-oxazolidone- (2) Manufactured by chlorination of 5- (4-aminophenyl) -3-tert-butyl-oxazolidone- (2).

Schmelzpunkt: 109-111°C. Melting point: 109-111 ° C.

c) 3-Athyl-5-(4-amino-3,5-dibrom-phenyl)-oxazolidon-(2) Hergestellt durch Bromierung von 3-Athyl-5-(4-amino-phenyl)-oxazolidon-(2). c) 3-Ethyl-5- (4-amino-3,5-dibromophenyl) -oxazolidone- (2) Prepared by bromination of 3-ethyl-5- (4-aminophenyl) -oxazolidone- (2).

0 Schmelzpunkt: 112-113°C. 0 Melting point: 112-113 ° C.

d) 5-(4-Amino-3,5-dibrom-phenyl)-3-methyl-oxazolidon-(2) Hergestellt durch Bromierung von 5-(4-Amino-phenyl)-3-methyl-oxazolidon-(2). d) 5- (4-Amino-3,5-dibromophenyl) -3-methyl-oxazolidone- (2) Prepared by bromination of 5- (4-aminophenyl) -3-methyl-oxazolidone- (2).

Schmelzpunkt: 95-97 0C. Melting point: 95-97 ° C.

e) 5-(4-Amino-3,5-dibrom-phenyl)-oxazolidon-(2) Hergestellt durch Bromierung von 5-(4 Amino-phenyl)-oxazolidon-(2). e) 5- (4-Amino-3,5-dibromophenyl) -oxazolidone- (2) Manufactured by Bromination of 5- (4 aminophenyl) -oxazolidone- (2).

Schmelzpunkt: 167-169,5 0C. Melting point: 167-169.5 ° C.

f) 5-(4-Amino-3,5-dichlor-phenyl)-oxazolidon-(2) Hergestellt durch Chlorierung von 5-(4-Amino-phenyl)-oxazolidon-(2). f) 5- (4-Amino-3,5-dichloro-phenyl) -oxazolidone- (2) Manufactured by Chlorination of 5- (4-aminophenyl) -oxazolidone- (2).

Schmelzpunkt: 157-159°C. Melting point: 157-159 ° C.

2.) Hergestellung der Endprodukte der Formel I: a) 1-(4-Amino-315-dichlor-phenyl)-2-tert.-butylamino-athanol 1 g (0,0033 Mol) 5-(4-Amino-3,5-dichlor-phenyl)-3-tert.-butyl-oxazolidon-(2) werden in 20 ccm Isopropanol gelöst und mit 2 ccm Wasser und 2 g Kaliumhydroxid versetzt. Die entstehende zweiphasige Lösung kocht man 24 Stunden am Rückfluß und bringt anschließend das 1-(4-Amino-3,5-dichlorphenyl)-2-tert.-butylamino-äthanol durch Zusatz von etwas Äthanol und Wasser zur Kristallisation.2.) Preparation of the end products of the formula I: a) 1- (4-Amino-315-dichloro-phenyl) -2-tert-butylamino-ethanol 1 g (0.0033 mol) of 5- (4-amino-3,5-dichloro-phenyl) -3-tert-butyl-oxazolidone- (2) dissolved in 20 cc of isopropanol and treated with 2 cc of water and 2 g of potassium hydroxide. The resulting two-phase solution is refluxed for 24 hours and then brought the 1- (4-amino-3,5-dichlorophenyl) -2-tert-butylamino-ethanol by adding something Ethanol and water for crystallization.

Ausbeute: 0,80 g (87,4 % d. Th.); 0 Schmelzpunkt: 116-119°C. Yield: 0.80 g (87.4% of theory); 0 Melting point: 116-119 ° C.

M.G.: 277,20 (C121118C12N20) Der.: C 52,01 H 6,55 N 10,10 Cl 25,57 Gef.: 51,70 6,110 9,85 25,00 Auf die gleiche Weise wurden durch saure oder alkalische Verseifung der entsprechenden Oxazolidone folgende Verbintlungen der allgemeinen Formel I hergestellt: a) 1-(4-Amino-3,5-dibrom-phenyl)-2-tert.-butylamino-äthanol Schmelzpunkt des Hydrochlorids: 219,5-2200C (Zers.) Hergestellt durch alkalische Verseifung von 5-(4-Amino-3,5-dibrom-phenyl)-3-tert.-butyl-oxazolidon-(2).M.G .: 277.20 (C121118C12N20) Der .: C 52.01 H 6.55 N 10.10 Cl 25.57 Found: 51.70 6.110 9.85 25.00 Were acidic or alkaline in the same way Saponification of the corresponding oxazolidones following the general compounds Formula I made: a) 1- (4-Amino-3,5-dibromophenyl) -2-tert-butylamino-ethanol Melting point of the hydrochloride: 219.5-2200C (dec.) Produced by alkaline Saponification of 5- (4-amino-3,5-dibromophenyl) -3-tert-butyl-oxazolidone- (2).

b) 2-Athylamino-1-(4-amino-3,5-dibrom-phenyl)-Sthanol Schmelzpunkt des Hydrochlorids: 174-175°C (Zers.) Hergestellt durch saure Verseifung von 3-Äthyl-5-(4-amino-3,5-dibrom-phenyl)-oxazolidon-(2).b) 2-Ethylamino-1- (4-amino-3,5-dibromophenyl) -thanol Melting point of the hydrochloride: 174-175 ° C (dec.) Prepared by acidic saponification of 3-ethyl-5- (4-amino-3,5-dibromophenyl) -oxazolidone- (2).

c) 1-(4-Amino-3s5-dibrom-phenyl)-2-methylamino-Sthanol Schmelzpunkt des Hydrochlorids: 210-216°C (Zers.) Ilergestellt durch saure Verseifung von 5-(4-Amino-3,5-dibromphenyl)-3-methyl-oxazolidon-(2).c) 1- (4-Amino-3s5-dibromophenyl) -2-methylamino-ethanol, melting point of the hydrochloride: 210-216 ° C. (decomp.) Produced by acidic saponification of 5- (4-amino-3,5-dibromophenyl) -3-methyl-oxazolidone- (2).

d) 2-Amino-1-(4-amino-3,5-dibrom-phenyl)-äthanol Schmelzpunkt des Hydrochlorids:214-216°C (Zers.) Hergestellt durch alkalische Verseifung von 5-(4-Amino-3,5-dibrom-phenyl)-oxazolidon-(2).d) 2-Amino-1- (4-amino-3,5-dibromophenyl) ethanol, melting point of Hydrochloride: 214-216 ° C (dec.) Prepared by alkaline saponification of 5- (4-amino-3,5-dibromophenyl) -oxazolidone- (2).

e) 2-Amino-1-(4-amino-3,5-dichlor-phenyl)-äthanol Schmelzpunkt des Ilydrochlorids: 199-204°C (Zers.) Hergestellt durch alkalische Verseifung von 5-(4-Amino-3,5-dichlor-phenyl)-oxazolidon-(2).e) 2-Amino-1- (4-amino-3,5-dichloro-phenyl) -ethanol melting point of the Ilydrochlorids: 199-204 ° C (dec.) Manufactured by alkaline saponification of 5- (4-amino-3,5-dichloro-phenyl) -oxazolidone- (2).

Claims (9)

Patentansprüche Claims W 3 Verfahren zur Herstellung von 11-Amino-3,5-dihalogenphenyl-Ethanolaminen der Formel I, in der Hal ein Chlor- oder Bromatom und R ein Wasserstoffatom oder einen Alkylrest mit 1 - 5 Kohlenstoffatomen bedeuten, sowie von deren physiologisch verträglichen Säureadditionssalzen mit anorganischen oder organischen Säuren, dadurch gekennzeichnet, daß ein Oxazolidon der Formel die Reste Final und R die oben erwähnten Bedeutungen auSweisen, sauer oder alkalisch hydrolysiert wird und die erhaltene Verbindung der Formel I gewünschtenfalls mit einer anorganischen oder organischen Säure in ihr Säureadditionssalz übergeführt wird.W 3 process for the preparation of 11-amino-3,5-dihalophenyl-ethanolamines of the formula I, in which Hal denotes a chlorine or bromine atom and R denotes a hydrogen atom or an alkyl radical having 1-5 carbon atoms, as well as their physiologically acceptable acid addition salts with inorganic or organic acids, characterized in that an oxazolidone of the formula the radicals Final and R have the abovementioned meanings, is hydrolyzed under acidic or alkaline conditions and the compound of the formula I obtained is, if desired, converted into its acid addition salt using an inorganic or organic acid. 2.) Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß die Hydrolyse mittels eines Alkalihydroxids in einem Lösungsmittel durchgeführt wird.2.) The method according to claim 1, characterized in that the hydrolysis is carried out by means of an alkali hydroxide in a solvent. 3.) Verfahren nach den Ansprüchen 1 wld 2, dadurch gekennzeichnet, daß als Lösungsmittel ein A"thylenglykoiäther oder ein Alkanol unter Zusatz von Wasser verwendet wird.3.) Process according to claims 1 wld 2, characterized in that that as a solvent an A "ethylene glycol ether or an alkanol with the addition of Water is used. 4.) Verfahren nach den Ansprüchen 1-3, dadurch gekennzeichnet, daß die Umsetzung bei der Siedetemperatur des verwendeten Lösungsmittels durchgeführt wird.4.) Process according to claims 1-3, characterized in that the reaction is carried out at the boiling point of the solvent used will. 5.) Neue Oxazolidone der Formel II, in der die Reste R und Hal wie im Anspruch 1 definiert sind.5.) New oxazolidones of the formula II, in which the radicals R and Hal are like are defined in claim 1. 6.) Neue Oxazolidone gemäß Anspruch 5, in denen R ein Wasserstoffatom, die Methyl-, Athyl- oder tert.-Butylgruppe bedeutet.6.) New oxazolidones according to claim 5, in which R is a hydrogen atom, denotes the methyl, ethyl or tert-butyl group. Verfahren zur Herstellung der neuen Oxazolidone de im Anspruch 5 angeführten allgemeinen Formel II, dadurch gekennzeichnet, daß ein Oxazolidon der allgemeinen Formel III, in der R die oben erwähnten Bedeutungen besitzt, chloriert oder bromiert wird.Process for the preparation of the new oxazolidones de general formula II given in claim 5, characterized in that an oxazolidone of the general formula III, in which R has the meanings mentioned above, is chlorinated or brominated. 8.) Verfahren nach Anspruch 7, dadurch gekennzeichnet, daß die Halogenierung mit mindestens 2 Mol Brom oder Chlor in einem Lösungsmittel durchgeführt wird.8.) The method according to claim 7, characterized in that the halogenation is carried out with at least 2 moles of bromine or chlorine in a solvent. 9.) Verfahren nach den Ansprüchen 7 und 8, dadurch gekennzeichnet, daß als Lösungmittel 50 bis 100%ige F.ssigsaure, Äthanol oder ein halogenierter Kohlenwasserstoff verwendet wird.9.) Process according to claims 7 and 8, characterized in that that as a solvent 50 to 100% F.ssigsaure, ethanol or a halogenated Hydrocarbon is used. 10,) Verfahren nach den Anspri5chen 7-9, d<:durcii gekennzeichnet, daß die Halogenierung bei Temperaturen zwischen 0 und 500C durchgefilhrt wird.10,) method according to claims 7-9, d <: characterized by, that the halogenation is carried out at temperatures between 0 and 500C.
DE2157040A 1971-11-17 1971-11-17 4-amino-3,5-dihalophenylethanolamines prepn - by hydrolysis of 5-(4-amino-3,5-dihalo-phenyl)-2-oxazolidones Pending DE2157040A1 (en)

Priority Applications (22)

Application Number Priority Date Filing Date Title
DE2157040A DE2157040A1 (en) 1971-11-17 1971-11-17 4-amino-3,5-dihalophenylethanolamines prepn - by hydrolysis of 5-(4-amino-3,5-dihalo-phenyl)-2-oxazolidones
JP10453671A JPS5512893B2 (en) 1971-11-17 1971-12-22
AT943572A AT320618B (en) 1971-11-17 1972-11-07 Process for the preparation of 4-amino-3,5-dihalophenyl-ethanolamines and their acid addition salts
AT1038373A AT320642B (en) 1971-11-17 1972-11-07 Process for the preparation of new oxazolidones
CH1654972A CH574903A5 (en) 1971-11-17 1972-11-14
YU2815/72A YU35870B (en) 1971-11-17 1972-11-14 Process for preparing 4-amino-3,5-dihalo-phenyl-ethanolamines
SU1847357A SU468398A3 (en) 1971-11-17 1972-11-14 The method of obtaining 4-amino-3,5-dihalophenylethanolamines
HUTO893A HU164697B (en) 1971-11-17 1972-11-15
ES408615A ES408615A1 (en) 1971-11-17 1972-11-15 Novel oxazolidone derivatives and preparation thereof
HUTO936A HU166034B (en) 1971-11-17 1972-11-15
DD166875A DD103640A5 (en) 1971-11-17 1972-11-15
DD174171*A DD108297A5 (en) 1971-11-17 1972-11-15
BG021865A BG20337A3 (en) 1971-11-17 1972-11-15 METHOD FOR OBTAINING 4-AMINO-3,5-DIHALOGEN-PHENYL-ETHANOLAMINE
RO7272820A RO68219A (en) 1971-11-17 1972-11-15 PROCEDURE FOR THE PREPARATION OF 4-AMINO-3,5-DIHALOGENE-PHENYL-ETANOLAMINE
CS7736A CS170454B2 (en) 1971-11-17 1972-11-15
PL1972158883A PL79757B1 (en) 1971-11-17 1972-11-16
CA156,600A CA987685A (en) 1971-11-17 1972-11-16 Process for the preparation of 4-amino-3,5-dihalogen-phenyl-ethanolamines
DK086574AA DK150851B (en) 1971-11-17 1974-02-18 OXAZOLIDON- (2) COMPOUNDS FOR USING INTERMEDIATES FOR THE PREPARATION OF 4-AMINO-3,5-DIHALOGEN-PHENYLETHANOLAMINES
SE7505550A SE405854B (en) 1971-11-17 1975-05-14 NEW OXAZOLIDONES
JP12337176A JPS5293767A (en) 1971-11-17 1976-10-14 Novel oxazolidone derivatives and preparation thereof
FI792528A FI792528A (en) 1971-11-17 1979-08-15 MOWER PROCESSING OIL FOR FARING
YU2525/79A YU40763B (en) 1971-11-17 1979-10-17 Process for preparing new oxazolidines

Applications Claiming Priority (1)

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DE2157040A DE2157040A1 (en) 1971-11-17 1971-11-17 4-amino-3,5-dihalophenylethanolamines prepn - by hydrolysis of 5-(4-amino-3,5-dihalo-phenyl)-2-oxazolidones

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DE2157040A1 true DE2157040A1 (en) 1973-05-24

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JP (2) JPS5512893B2 (en)
AT (2) AT320642B (en)
BG (1) BG20337A3 (en)
CA (1) CA987685A (en)
CH (1) CH574903A5 (en)
CS (1) CS170454B2 (en)
DD (2) DD103640A5 (en)
DE (1) DE2157040A1 (en)
DK (1) DK150851B (en)
ES (1) ES408615A1 (en)
HU (2) HU164697B (en)
PL (1) PL79757B1 (en)
RO (1) RO68219A (en)
SE (1) SE405854B (en)
SU (1) SU468398A3 (en)
YU (2) YU35870B (en)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2354961A1 (en) * 1973-11-02 1975-06-05 Thomae Gmbh Dr K Aminophenylethanolamines and oxazolidines - beta-2-mimetics, beta-1-inhibitors, analgesics, uterospasmolytics, and antispastics
US5059422A (en) * 1985-07-29 1991-10-22 American Cyanamid Company Continuous release phenylethanolamine derivative compositions
US5169633A (en) * 1985-07-29 1992-12-08 American Cyanamid Company Continuous release phenylethanolamine derivative compositions
US10288602B2 (en) 2013-01-08 2019-05-14 Atrogi Ab Screening method, a kit, a method of treatment and a compound for use in a method of treatement
US11357757B2 (en) 2017-09-13 2022-06-14 Atrogi Ab Heteroaryl substituted beta-hydroxyethylamines for use in treating hyperglycaemia
US11427539B2 (en) 2017-09-13 2022-08-30 Atrogi Ab Beta-hydroxy heterocyclic amines and their use in the treatment of hyperglycaemia
US11648216B2 (en) 2017-09-13 2023-05-16 Atrogi Ab Fluorophenyl beta-hydroxyethylamines and their use in the treatment of hyperglycaemia
US11793774B2 (en) 2017-09-13 2023-10-24 Atrogi Ab Chiral beta-hydroxyethylamines and their use in the treatment of hyperglycemia
WO2023203223A1 (en) 2022-04-22 2023-10-26 Atrogi Ab Combinations of beta 2-adrenergic receptor agonists and beta 3-adrenergic receptor agonists, and medical uses thereof
WO2024153813A1 (en) 2023-01-20 2024-07-25 Atrogi Ab Beta 2-adrenergic receptor agonists for treatment or prevention of muscle wasting
WO2024170727A1 (en) 2023-02-16 2024-08-22 Atrogi Ab Combinations of beta 2-adrenergic receptor agonists and metformin for use in treating obesity and reducing body fat
WO2024184408A1 (en) 2023-03-06 2024-09-12 Atrogi Ab Combination of beta-2-adrenergic receptor agonists and glp-1 receptor agonists for use in treating hyperglycaemia

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1618005A1 (en) * 1966-09-22 1971-09-09 Thomae Gmbh Dr K Process for the preparation of new amino-dihalogen-phenyl-ethylamines

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2354961A1 (en) * 1973-11-02 1975-06-05 Thomae Gmbh Dr K Aminophenylethanolamines and oxazolidines - beta-2-mimetics, beta-1-inhibitors, analgesics, uterospasmolytics, and antispastics
US5059422A (en) * 1985-07-29 1991-10-22 American Cyanamid Company Continuous release phenylethanolamine derivative compositions
US5169633A (en) * 1985-07-29 1992-12-08 American Cyanamid Company Continuous release phenylethanolamine derivative compositions
US10288602B2 (en) 2013-01-08 2019-05-14 Atrogi Ab Screening method, a kit, a method of treatment and a compound for use in a method of treatement
US11648216B2 (en) 2017-09-13 2023-05-16 Atrogi Ab Fluorophenyl beta-hydroxyethylamines and their use in the treatment of hyperglycaemia
US11427539B2 (en) 2017-09-13 2022-08-30 Atrogi Ab Beta-hydroxy heterocyclic amines and their use in the treatment of hyperglycaemia
US11357757B2 (en) 2017-09-13 2022-06-14 Atrogi Ab Heteroaryl substituted beta-hydroxyethylamines for use in treating hyperglycaemia
US11793774B2 (en) 2017-09-13 2023-10-24 Atrogi Ab Chiral beta-hydroxyethylamines and their use in the treatment of hyperglycemia
US12036210B2 (en) 2017-09-13 2024-07-16 Atrogi Ab Heteroaryl substituted beta-hydroxyethylamines for use in treating hyperglycaemia
WO2023203223A1 (en) 2022-04-22 2023-10-26 Atrogi Ab Combinations of beta 2-adrenergic receptor agonists and beta 3-adrenergic receptor agonists, and medical uses thereof
WO2024153813A1 (en) 2023-01-20 2024-07-25 Atrogi Ab Beta 2-adrenergic receptor agonists for treatment or prevention of muscle wasting
WO2024170727A1 (en) 2023-02-16 2024-08-22 Atrogi Ab Combinations of beta 2-adrenergic receptor agonists and metformin for use in treating obesity and reducing body fat
WO2024184408A1 (en) 2023-03-06 2024-09-12 Atrogi Ab Combination of beta-2-adrenergic receptor agonists and glp-1 receptor agonists for use in treating hyperglycaemia

Also Published As

Publication number Publication date
HU164697B (en) 1974-03-28
ES408615A1 (en) 1975-10-01
HU166034B (en) 1974-12-28
YU281572A (en) 1981-02-28
AT320642B (en) 1975-02-25
CH574903A5 (en) 1976-04-30
CS170454B2 (en) 1976-08-27
YU40763B (en) 1986-06-30
PL79757B1 (en) 1975-06-30
JPS4857941A (en) 1973-08-14
SE7505550L (en) 1975-05-14
AT320618B (en) 1975-02-25
SE405854B (en) 1979-01-08
DD108297A5 (en) 1974-09-12
JPS5293767A (en) 1977-08-06
SU468398A3 (en) 1975-04-25
YU252579A (en) 1983-01-21
RO68219A (en) 1980-03-15
YU35870B (en) 1981-08-31
BG20337A3 (en) 1975-11-05
JPS5422977B2 (en) 1979-08-10
DD103640A5 (en) 1974-02-05
JPS5512893B2 (en) 1980-04-04
DK150851B (en) 1987-07-06
CA987685A (en) 1976-04-20

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