NO127351B - - Google Patents

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Publication number
NO127351B
NO127351B NO03755/71*[A NO375571A NO127351B NO 127351 B NO127351 B NO 127351B NO 375571 A NO375571 A NO 375571A NO 127351 B NO127351 B NO 127351B
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Norway
Prior art keywords
formula
acid
compounds
phenyl
imidazoline
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NO03755/71*[A
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Norwegian (no)
Inventor
Werner Metlesics
Leo Henryk Sternbach
Original Assignee
Hoffmann La Roche
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Priority claimed from US639315A external-priority patent/US3888846A/en
Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of NO127351B publication Critical patent/NO127351B/no

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D233/22—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Structures Of Non-Positive Displacement Pumps (AREA)

Description

Analogifremgangsmåte for fremstilling av Analogy method for the production of

terapeutisk aktive, aromatiske forbindelser. therapeutically active, aromatic compounds.

Nærværende oppfinnelse vedrorer en analogifremgangsmåte for fremstilling av nye, terapeutisk aktive, aromatiske forbindelser med den generelle formel i hvilke formler B betyr en alkylengruppe med 2-4 karbonatomer, The present invention relates to an analogous method for the production of new, therapeutically active, aromatic compounds with the general formula in which formulas B means an alkylene group with 2-4 carbon atoms,

R^ halogen eller hydrogen, og R^ halogen or hydrogen, and

og R^ hydrogen, halogen, lavere alkyl, lavere alkoksy eller trifluormetyl. and R 1 is hydrogen, halogen, lower alkyl, lower alkoxy or trifluoromethyl.

De to tautomere isomere kan ved protohvandring gå over i hver-andre, hvilket kan fremstilles skjematisk som folger: The two tautomeric isomers can change into each other by protomigration, which can be represented schematically as follows:

Den foreliggende oppfinnelse vedrorer også fremstillingen av syreaddisjonssalter av de nevnte forbindelser. The present invention also relates to the production of acid addition salts of the aforementioned compounds.

Egnede salter av forbindelser med formlene I og II er slike med ikke-giftige, organiske og uorganiske syrer. Egnede organiske syrer er f.eks. maleinsyre, fumarsyre, askorbinsyre, vinsyre, salicylsyre, ravsyre, sitronsyre og lignende. Egnede uorganiske syrer er f.eks. halogenhydronsyrer, som klorhydrogensyre og bromhydrogensyre, svovelsyre, sulfaminsyre, fosforsyre og lignende. Syreaddisjonssaltene fremstilles efter kjente, for fag-mannen vanlige metoder. Suitable salts of compounds of formulas I and II are those with non-toxic organic and inorganic acids. Suitable organic acids are e.g. maleic acid, fumaric acid, ascorbic acid, tartaric acid, salicylic acid, succinic acid, citric acid and the like. Suitable inorganic acids are e.g. halohydronic acids, such as hydrochloric acid and hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid and the like. The acid addition salts are produced according to known methods common to those skilled in the art.

Fremgangsmåten ifolge oppfinnelsen for fremstilling av aromatiske forbindelser med formlene I og II er karakterisert ved at man behandler en forbindelse med formel The process according to the invention for producing aromatic compounds with formulas I and II is characterized by treating a compound with formula

hvor B, R-^, og R^ har foran angitte betydning, med et oksydasjonsmiddel, hvis onsket overforer en oppnådd forbindelse til et syreaddisjonssalt. where B, R-^, and R^ have the meanings indicated above, with an oxidizing agent, if desired, converts an obtained compound into an acid addition salt.

Fremgangsmåten ifolge oppfinnelsen for fremstilling av forbindelser med formlene I og II er anskueliggjort i det folgende reaksjonsskjema: hvor X betyr halogen, fortrinnsvis klor, jod eller brom eller en lignende avspaltbar gruppe, som en mesyloksy-, tosyloksygruppe og lignende. The process according to the invention for producing compounds with the formulas I and II is visualized in the following reaction scheme: where X means halogen, preferably chlorine, iodine or bromine or a similar cleavable group, such as a mesyloxy, tosyloxy group and the like.

Oksydasjonen kan f.eks. skje ved behandling med gassformet oksy-gen eller ved hjelp av kromtrioksyd i eddiksyre og lignende. The oxidation can e.g. take place by treatment with gaseous oxygen or by means of chromium trioxide in acetic acid and the like.

Reaksjonen gjennomfores fortrinnsvis i nærvær av et organisk opplosningsmiddel, f.eks. hydrokarboner, som benzen, toluen eller lignende, alkankarboksylsyrer, som eddiksyre, propionsyre og lignende, etere, alkoholer og opplosningsmidler, som dimetyl-formamid og lignende. På egnet måte arbeider man ved romtemperatur eller ved forhoyede temperaturer, fortrinnsvir ved en tempe-ratur mellom 20° og 100°C. 1-fenyl-2-aminoalkylisoindolinene fremstilles fra dioler med formel IV over en diester med formel V. Diesteren oppnås efter vanlige forestringsmetoder, f.eks. ved behandling av diolet med et vanlig forestringsmiddel, som fosforhalogenid, tionylhalogenid, tosylhalogenid og lignende. Diesteren med formel V kan igjen overfores til 1-fenyl-2-amino-alkylisoindolinet med formel III ved kondensasjon med et diamin med formel VI. The reaction is preferably carried out in the presence of an organic solvent, e.g. hydrocarbons, such as benzene, toluene or the like, alkanecarboxylic acids, such as acetic acid, propionic acid and the like, ethers, alcohols and solvents, such as dimethylformamide and the like. It is suitable to work at room temperature or at elevated temperatures, preferably at a temperature between 20° and 100°C. The 1-phenyl-2-aminoalkylisoindolines are prepared from diols of formula IV over a diester of formula V. The diester is obtained by usual esterification methods, e.g. by treating the diol with a common esterification agent, such as phosphorus halide, thionyl halide, tosyl halide and the like. The diester of formula V can again be transferred to the 1-phenyl-2-amino-alkylisoindoline of formula III by condensation with a diamine of formula VI.

Reaksjonen med diaminet skjer vanligvis ved tilsetning av diesteren med formel V til diaminet ved romtemperatur. Fortrinnsvis anvender man et stort molart overskudd av diaminet. Reaksjonen kan imidlertid også gjennomfores ved temperaturer over eller under romtemperatur, av praktiske grunner er det dog fore-trukket å arbeide ved temperaturer mellom 0° og 100°C. Fortrinnsvis arbeider man i nærvær av et organisk opplosningsmiddel f.eks. benzen, metylenklorid, eter, tetrahydrofuran og lignende. I tilfelle av en eller begge av reaksjonskomponentene er flyten-de ved de anvendte betingelser, kan man imidlertid også arbeide uten opplosningsmiddel. The reaction with the diamine usually takes place by adding the diester of formula V to the diamine at room temperature. A large molar excess of the diamine is preferably used. However, the reaction can also be carried out at temperatures above or below room temperature, for practical reasons it is however preferred to work at temperatures between 0° and 100°C. Preferably, you work in the presence of an organic solvent, e.g. benzene, methylene chloride, ether, tetrahydrofuran and the like. In the case of one or both of the reaction components being liquid under the conditions used, however, one can also work without a solvent.

Forbindelsene med formel I og II som oppnås efter oppfinnelsen og deres farmasoytisk anvendelige syreaddisjonssalter har psy-ko stimulerende virkning. Efter f.eks. oral administrasjon til dyr, som mus, forårsaker de en direkte stimulerende, langvarig virkning. Eksempler på forbindelser med formel I og II, som er provet og ved provene vedrorende psykostimulerende virkning fun- The compounds of formula I and II which are obtained according to the invention and their pharmaceutically usable acid addition salts have a psychostimulant effect. After e.g. oral administration to animals, such as mice, they cause a direct stimulatory, long-lasting effect. Examples of compounds with formula I and II, which have been tested and, when tested, regarding psychostimulant effects

net hoyaktive, er f.eks. net highly active, are e.g.

2-(2-benzoylfenyl)-2-imidazolin; 2-(2-benzoylphenyl)-2-imidazoline;

5-(4-klorfenyl)-2,3-dihydro-5-hydroksy-5H-imidazo-[2,l-a]-isoindol; 5-(4-chlorophenyl)-2,3-dihydro-5-hydroxy-5H-imidazo-[2,1-a]-isoindole;

2,3-dihydro-5-hydroksy-5-(4-metoksyfenyl)-5H-imidazo-[2,l-a]-isoindol; 2,3-dihydro-5-hydroxy-5-(4-methoxyphenyl)-5H-imidazo-[2,1-a]-isoindole;

2,3,4,5-tetrahydro-7-hydroksy-7-fenyl-7H-diazepino-[2,l-a]-isoindol; 2,3,4,5-tetrahydro-7-hydroxy-7-phenyl-7H-diazepino-[2,1-a]-isoindole;

2,3-dihydro-5-metoksy-5-fenyl-5H-imidazo[2,1-a]- 2,3-dihydro-5-methoxy-5-phenyl-5H-imidazo[2,1-a]-

isoindol. isoindole.

Forbindelsene med formlene I og II egner seg derfor som psyko-stimulantia for behandling ved depressjoner, f.eks. ved tilfel- The compounds with formulas I and II are therefore suitable as psycho-stimulants for treatment of depression, e.g. in case of

ler av enkle depresjoner eller ved "kronisk-nervos utmattelse. laughs at simple depressions or at "chronic-nervous exhaustion.

Dessuten egner forbindelser med formel II seg som analgetika. Dessuten viser de anti-inflammatorisk, anti-odem- og muskel-relakserende virkning. F.eks. viser 2-(2-benzoylfenyl)-2-imida-zolin i standardprover for analgetisk virkning utpreget aktivi- Furthermore, compounds of formula II are suitable as analgesics. In addition, they show anti-inflammatory, anti-edema and muscle-relaxing effects. E.g. shows 2-(2-benzoylphenyl)-2-imidazoline in standard samples for analgesic effect markedly active

tet. Forbindelser med formel II er videre virksomme som appe-titthemmere. Dessuten har de kardiovaskulære egenskaper. tight. Compounds of formula II are further effective as appetite inhibitors. Moreover, they have cardiovascular properties.

Forbindelser med formel II er dessuten virksomme fungicider. Det Compounds of formula II are also effective fungicides. The

ble f.eks. funnet at de er virksomme in vitro mot Candida albi- was e.g. found to be active in vitro against Candida albi-

cans, Microsporum audouini og Trichophyton mentagrophytes. Dis- cans, Microsporum audouini and Trichophyton mentagrophytes. Haze-

se forbindelser kan derfor anvendes som fungicider for behand- se compounds can therefore be used as fungicides for treat-

ling av patogene sykdommer, som fremkalles av disse organismer. F.eks. kan man anvende dem for behandling av infektiose sopp-sykdommer, som f.eks. Moniliasis og Dermatocycosis. For behand- ling of pathogenic diseases, which are caused by these organisms. E.g. can they be used for the treatment of infectious fungal diseases, such as e.g. Moniliasis and Dermatocycosis. For treat-

ling av soppinfeksjoner kan forbindelser med formel I eller far-masøytisk anvendelige salter av disse anvendes i et vanlig bære-middel for maksimal administrasjon. ling fungal infections, compounds of formula I or pharmaceutically usable salts thereof can be used in a conventional carrier for maximum administration.

De nye sluttprodukter som oppnås ifolge oppfinnelsen er for det meste hvite, luktfrie krystaller med smeltepunkter omkring 200°C. The new end products obtained according to the invention are mostly white, odorless crystals with melting points around 200°C.

De har basiske egenskaper og kan derfor lett fremstilles i form They have basic properties and can therefore be easily produced in shape

av deres syreaddisjonssalter. Disse salter er karakteristiske hvite luktfrie krystaller, som er opploselige i vann og som under normale betingelser viser god stabilitet. of their acid addition salts. These salts are characteristic white odorless crystals, which are soluble in water and which under normal conditions show good stability.

Sluttproduktene ved fremgangsmåten ifolge oppfinnelsen og fortrinnsvis deres syreaddisjonssalter kan administreres i form av farmasoytiske preparater enteralt eller parenteralt. Parenterale adminstrasjonsformer inneholder vanligvis mindre aktiv substans enn preparater for enteral, d.v.s. for oral anvendelse. For oral administrasjon fremstilles fortrinnsvis tabletter, kapsler og lignende. Denne orale administrasjon kan enten be-virke en umiddelbar eller en langvarig frigjoring av den aktive substans. Gener^-t anvender man for disses fremstilling farma-søytisk anvendbare ledsagermaterialer i en mengde på 60-98 vekts% av preparatet for den orale dosering. The end products of the method according to the invention and preferably their acid addition salts can be administered in the form of pharmaceutical preparations enterally or parenterally. Parenteral forms of administration usually contain less active substance than preparations for enteral use, i.e. for oral use. For oral administration, tablets, capsules and the like are preferably prepared. This oral administration can either cause an immediate or a prolonged release of the active substance. Generally, for their production, pharmaceutically usable companion materials are used in an amount of 60-98% by weight of the preparation for the oral dosage.

Generelt bringes de ifolge oppfinnelsen fremstilte forbindelser med vanlige inerte ledsagerstoffer til en for den enterale og parenterale administrasjon egnet doseringsform efter vanlige metoder. Disse kan inneholde konserveringsmiddel, stabilise-ring smiddel, fuktnings- eller emulgeringsmiddel, salter til for-andring av det osmotiske trykk, puffer og liknende. Hvis onsket kan de også inneholde ytterligere andre terapeutisk verdifulle stoffer. In general, the compounds produced according to the invention are brought to a dosage form suitable for enteral and parenteral administration with usual inert accompanying substances according to usual methods. These may contain preservatives, stabilizers, wetting or emulsifying agents, salts to change the osmotic pressure, buffers and the like. If desired, they can also contain further other therapeutically valuable substances.

I det folgende eksempel er alle smeltepunkter angitt i Celsius-grader . In the following example, all melting points are given in degrees Celsius.

Smeltepunkter ved hvilke spaltning inntrer, kan variere med ca. Melting points at which cleavage occurs can vary by approx.

- 10° avhengig av oppvarmningen. - 10° depending on the heating.

Eksempel 1 Example 1

En opplosning av 127 g (0,59 mol) 2-hydroksymetylbenzhydrol opploses i 900 ml benzen, 80 g vannfritt magnesiumsulfat til-fores, og blandingen avkjoles i et isbad. Hydrogenbromid innle-des inntil metning gjennom den rorte opplosning, noe som varer i ca. 30 minutter. I lopet av denne tid holdes temperaturen i opplosningen på 15 - 18°. Isbadet fjernes og temperaturen sti-ger i lopet av 1 time til 35°. Blandingen holdes i 1 time ved 40-45° på vannbadet. I lopet av hele denne tid ledes hydrogenbromid gjennom opplosningen for å holde den mettet. Blandingen filtreres, og opplosningen inndampes i vakuum, idet man oppnår en rod olje, som opploses i 200 ml benzen og i lopet av 15 minutter tilsettes til 342 g (5,7 mol) etylendiamin. I lopet av tilsetningen rores blandingen og avkjoles for å holde temperaturen på 40°. Blandingen rores i 70 minutter ved 25°. Man oppnår to skikt, som skilles fra. Benzenfasen vaskes med vann og inndampes i vakuum. Den tilbakeblivende olje opploses i 250 ml eter. Opplosningen ekstraheres to ganger med 300 ml kald l-n saltsyre. Den sure fase innstilles alkalisk med vandig natrium-hydroksydopplosning og ekstraheres med 350 ml eter. Den eteriske opplosning vaskes med 250 ml vann, torkes og inndampes. Man. oppnår en ravfarget olje, som krystalliserer ved kratsing. Denne substans, 2-(2-aminoetyl)-1-fenylisoindolin, smelter ved 45°. A solution of 127 g (0.59 mol) of 2-hydroxymethylbenzhydrol is dissolved in 900 ml of benzene, 80 g of anhydrous magnesium sulfate are added, and the mixture is cooled in an ice bath. Hydrogen bromide is introduced through the stirred solution until saturation, which lasts for approx. 30 minutes. During this time, the temperature in the solution is kept at 15 - 18°. The ice bath is removed and the temperature rises over the course of 1 hour to 35°. The mixture is kept for 1 hour at 40-45° in the water bath. Throughout this time, hydrogen bromide is passed through the solution to keep it saturated. The mixture is filtered, and the solution is evaporated in vacuo, obtaining a red oil, which is dissolved in 200 ml of benzene and added to 342 g (5.7 mol) of ethylenediamine over the course of 15 minutes. During the addition, the mixture is stirred and cooled to keep the temperature at 40°. The mixture is stirred for 70 minutes at 25°. Two layers are obtained, which are separated. The benzene phase is washed with water and evaporated in vacuo. The remaining oil is dissolved in 250 ml of ether. The solution is extracted twice with 300 ml of cold 1-n hydrochloric acid. The acidic phase is made alkaline with aqueous sodium hydroxide solution and extracted with 350 ml of ether. The ethereal solution is washed with 250 ml of water, dried and evaporated. Mon. obtains an amber colored oil, which crystallizes on scratching. This substance, 2-(2-aminoethyl)-1-phenylisoindoline, melts at 45°.

En opplosning av 3,3 g kromtrioksyd og 5,9 g ( 2-( 2-aminoetyl )-l-fenylisoindolin i 250 ml eddiksyre rores i 18 timer ved 55-60°. Opplosningen avkjoles, helles på is og innstilles alkalisk. Et-ter ekstraksjon med metylenklorid og fjerning av opplosnings-midlet oppnår man en brun olje, som krystalliserer delvis. Et-ter omkrystallisasjon fra en blanding av kloroform og etylåce-tat oppnår man 2-(2-benzoylfenyl)-2-imidazolin som hvite pris-mer med smeltepunkt 194-196° (spaltning). A solution of 3.3 g of chromium trioxide and 5.9 g of (2-(2-aminoethyl)-l-phenylisoindoline in 250 ml of acetic acid is stirred for 18 hours at 55-60°. The solution is cooled, poured onto ice and made alkaline. A After extraction with methylene chloride and removal of the solvent, a brown oil is obtained, which partially crystallizes. After recrystallization from a mixture of chloroform and ethyl acetate, 2-(2-benzoylphenyl)-2-imidazoline is obtained as a white product -mer with melting point 194-196° (decomposition).

Eksempel 2 Example 2

På analog måte til eksempel 1 kan de folgende forbindelser fremstilles: 2-[2'-(4-klorbenzoyl)fenyl]-2-imidazolin, s.p. 178-180° In an analogous manner to example 1, the following compounds can be prepared: 2-[2'-(4-chlorobenzoyl)phenyl]-2-imidazoline, m.p. 178-180°

(spaltning) (fission)

2-[2'-(4-brombenzoyl)fenylJ-2-imidazolin, s.p. 187-189° 2-[2'-(4-bromobenzoyl)phenyl J-2-imidazoline, m.p. 187-189°

(spaltning) (fission)

2-[2'-(4-metoksybenzoyl)fenylJ-2-imidazolin, s.p. 171-174° 2-[2'-(4-Methoxybenzoyl)phenyl J-2-imidazoline, m.p. 171-174°

(spaltning) (fission)

2-[2'-(2-klorbenzoyl)fenyl]-2-imidazolin, s.p. 180-181° 2-[2'-(2-chlorobenzoyl)phenyl]-2-imidazoline, m.p. 180-181°

(spaltning) (fission)

2-[4'-klor-2<1->benzoylfenyl]-2-imidazolin, s.p. 200-202° 2-[4'-chloro-2<1->benzoylphenyl]-2-imidazoline, m.p. 200-202°

(spaltning) (fission)

2,3,4,5-tetrahydro-7-hydroksy-7-fenyl-7H-diazepino[2,l-a]iso-indol, s.p. 216-220 (spaltning) 2-[21-(3-trifluormetylbenzoyl)fenylJ-2-imidazolin, s.p. 199-20 2° (spaltning). 2,3,4,5-tetrahydro-7-hydroxy-7-phenyl-7H-diazepino[2,1-a]iso-indole, m.p. 216-220 (cleavage) 2-[21-(3-trifluoromethylbenzoyl)phenyl J-2-imidazoline, m.p. 199-20 2° (cleavage).

Claims (1)

Analogifremgangsmåte for fremstilling av terapeutisk aktive, aromatiske forbindelser med formelAnalogy method for the preparation of therapeutically active, aromatic compounds of formula henholdsvis av disses tautomere isomerer med formel i hvilke formler B betyr en alkylengruppe med 2-4 karbonatomer,R^ halogen eller hydrogen, og R 3 og R. hydrogen, halogen, lavere alkyl, lavere alkoksy eller trifluormetyl, karakterisert ved at man behandler en forbindelse med formel hvor B, R^, R^ og R^ har foran angitte betyd-ninger, med et oksydasjonsmiddel, og hvis onsket overforer en oppnådd forbindelse til et syreaddisjonssalt.respectively of their tautomeric isomers with formula in which formulas B means an alkylene group with 2-4 carbon atoms, R^ halogen or hydrogen, and R 3 and R. hydrogen, halogen, lower alkyl, lower alkoxy or trifluoromethyl, characterized by treating a compound with a formula where B, R^, R^ and R^ have the above meanings, with an oxidizing agent, and if desired, converts an obtained compound into an acid addition salt.
NO03755/71*[A 1967-03-30 1971-10-12 NO127351B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US62696567A 1967-03-30 1967-03-30
US639315A US3888846A (en) 1967-03-30 1967-05-18 Process for 2(2-(1,3-diazacycloalk-2-enyl))benzophenone derivatives and 1,3-diazacycloalkenyl(2,1-a)isoindole derivatives

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NO127351B true NO127351B (en) 1973-06-12

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NO1212/68A NO124111B (en) 1967-03-30 1968-03-29
NO03753/71*[A NO127239B (en) 1967-03-30 1971-10-12
NO03754/71*[A NO127350B (en) 1967-03-30 1971-10-12
NO03752/71*[A NO127238B (en) 1967-03-30 1971-10-12
NO03755/71*[A NO127351B (en) 1967-03-30 1971-10-12

Family Applications Before (4)

Application Number Title Priority Date Filing Date
NO1212/68A NO124111B (en) 1967-03-30 1968-03-29
NO03753/71*[A NO127239B (en) 1967-03-30 1971-10-12
NO03754/71*[A NO127350B (en) 1967-03-30 1971-10-12
NO03752/71*[A NO127238B (en) 1967-03-30 1971-10-12

Country Status (8)

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JP (2) JPS4843360B1 (en)
ES (1) ES352173A1 (en)
IE (1) IE31999B1 (en)
IL (1) IL29651A (en)
MY (1) MY7300459A (en)
NO (5) NO124111B (en)
SE (1) SE346318B (en)
YU (1) YU33929B (en)

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Publication number Priority date Publication date Assignee Title
JPS50125392U (en) * 1974-03-30 1975-10-14

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IE31999B1 (en) 1973-03-07
YU33929B (en) 1978-09-08
NO127238B (en) 1973-05-28
IE31999L (en) 1968-09-30
SE346318B (en) 1972-07-03
NO127239B (en) 1973-05-28
YU71768A (en) 1978-02-28
IL29651A (en) 1972-07-26
JPS4843360B1 (en) 1973-12-18
NO127350B (en) 1973-06-12
MY7300459A (en) 1973-12-31
ES352173A1 (en) 1969-10-01
NO124111B (en) 1972-03-06
JPS5017479B1 (en) 1975-06-20

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