NO792908L - 9,10-dihydro-9.10-metanoantracenderivat egnet som utgangsmaterial for fremstilling av terapeutisk aktive forbindelser, samt fremgangsmaate for fremstilling av dette derivat - Google Patents
9,10-dihydro-9.10-metanoantracenderivat egnet som utgangsmaterial for fremstilling av terapeutisk aktive forbindelser, samt fremgangsmaate for fremstilling av dette derivatInfo
- Publication number
- NO792908L NO792908L NO79792908A NO792908A NO792908L NO 792908 L NO792908 L NO 792908L NO 79792908 A NO79792908 A NO 79792908A NO 792908 A NO792908 A NO 792908A NO 792908 L NO792908 L NO 792908L
- Authority
- NO
- Norway
- Prior art keywords
- dihydro
- preparation
- derivative
- methanoanthracene
- starting material
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 8
- 239000007858 starting material Substances 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title description 4
- 230000001225 therapeutic effect Effects 0.000 title description 2
- YEMCWAQXCZYBBW-UHFFFAOYSA-N tetracyclo[6.6.1.02,7.09,14]pentadeca-2,4,6,9,11,13-hexaene Chemical class C12=CC=CC=C2C2CC1C1=CC=CC=C12 YEMCWAQXCZYBBW-UHFFFAOYSA-N 0.000 claims description 8
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 5
- 229910017604 nitric acid Inorganic materials 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- ZAELYRWEXINIKF-UHFFFAOYSA-N ctk2f1535 Chemical compound C12=CC=CC=C2C2(C=O)C3=CC=CC=C3C1C2 ZAELYRWEXINIKF-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000008707 rearrangement Effects 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 2
- 238000006238 Demjanov rearrangement reaction Methods 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000006462 rearrangement reaction Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- -1 9-formyl-9,10-dihydro-9,10-methanoanthracene compound Chemical class 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical class CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000006680 Reformatsky reaction Methods 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- UYXAWHWODHRRMR-UHFFFAOYSA-N hexobarbital Chemical compound O=C1N(C)C(=O)NC(=O)C1(C)C1=CCCCC1 UYXAWHWODHRRMR-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000012948 isocyanate Chemical class 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000004304 potassium nitrite Substances 0.000 description 1
- 235000010289 potassium nitrite Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 201000003004 ptosis Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229960005333 tetrabenazine Drugs 0.000 description 1
- XVWGGWYDDICSQC-UHFFFAOYSA-N tetracyclo[6.6.1.02,7.09,14]pentadeca-1,3,5,7,9,11,13-heptaene Chemical compound C1=CC=CC2=C3C4=CC=CC=C4C(=C12)C3 XVWGGWYDDICSQC-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
- C07C47/235—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
- C07C47/235—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings
- C07C47/238—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings having unsaturation outside the aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/38—Unsaturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings
- C07C47/453—Unsaturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
- C07C57/50—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid containing condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/16—Unsaturated compounds
- C07C61/39—Unsaturated compounds containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
Description
9,10-dihydro-9,10-metanoantracenderivat egnet
som utgangsmaterial for fremstilling av terapeutisk
aktive forbindelser, samt fremgangsmåte for frem-
stilling av dette derivat.
Foreliggende oppfinnelse vedrører et 9,10-dihydro-9,10-metanoantracederivat egnet som utgangsmaterial for fremstilling av terapeutisk aktive 9-aminoalkyl-metanoantracener, og det særegne ved derivatet i henhold til oppfinnelsen er at det utgjøres av 9-formyl-9,10-dihydro-9,10-metanoantracen med formel 1. Oppfinnelsen vedrører også en fremgangsmåte for fremstilling av det nevnte derivat, og det særegne ved fremgangsmåten i henhold til oppfinnelsen er at 9-amino-12-hydroksy-9,10-dihydro-9,10-etanoantracen med formel 11
behandles med salpetersyrling eller metallnitrit i surt medium.
Disse trekk ved oppfinnelsen fremgår av patentkravene.
Forbindelsen med formel (1) er egnet for fremstilling av nye, terapeutisk aktive 9-aminoalkyl-metanoantracen-derivater med den generelle formel
hvori A er C^-C^alkylen eller C^-C^alkenylen og R. og R-
er hver hydrogen, C^~C4alkyl, C^- C^ alkenyl, C^-C^alkynyl, C3~C6 cykloalkyl (C^-C^) alkyl, ar(C-^-C^)alkyl eller polyhalo (C2_C^)alkyl, eller danner sammen med det tilstøtende nitro-genatom en 5- til 7-leddet nitrogenholdig heterocyklisk ring som kan inneholde ét ytterligere heteroatom, og deres ikke-giftige salter, idet slike forbindelser er nyttige som anti-angstmidler, anti-depressiva, og kan anvendes som et sterkt beroligende middel, anti-histaminmiddel eller anti-allergimiddel.
Slike nye forbindelser kan fordelaktig fremstilles ut fra
det nye utgangsmaterial med formel (1), nemlig 9-formyl-9,10-dihydro-■9,10-metanoantracen ved hjelp av forskjellige metoder, og det vises i sådan forbindelse til de analogifremgangsmåter som er om-handlet i norsk patentansøkning 75.4237.
9,10-dihydro-9,10-metanoantracen-skjelettet har vært kjent siden 1920 og det er foretatt noen kjemiske studier vedrørende 9,10-dihydro-9,10-metanoantracen-derivatene, men det er ikke utgitt noen rapporter hverken om syntesen av 9-aminoalkyl-9,10-dihydro-9,10-metanoantracen-derivatene eller noen farma-kologisk undersøkelse vedrørende 9,10-dihydro-9,10-metanoantracen-derivatene .
Selv om en mengde dibenzotricykliske forbindelser er kjent og enkelte av dem nå anvendes klinisk som medisiner, spesielt som psykotrope stoffer, har ikke hvilke som helst dibenzotricykliske forbindelser med en 9,10-dihydro-9,10-metanoantracen-ring som det dibenzotricykliske skjelett vært anvendt for dette formål. Muligheten for fremstilling av de terapeutisk aktive 9-aminoalkyl-metanoantracenderivatene er til-veiebragt ved syntetisering av det.nøkkel-utgangsmaterial som utgjør den foreliggende oppfinnelse, nemlig 9-formyl-9,10-dihydro-9,10-metanoantracen med formel (1)
9-aminoalkyl-metanoantracenderivatene er nye og fremviser karakteristisk en lang rekke verdifulle farmakologiske virkninger, spesielt på det sentrale nervesystem og det auto-nome nervesystem. Mer spesielt viser 9-aminoalkyl-metanoantracen-derivatene med formel (1) hvori A er metylen som kan være substituert med alkyl med 1 til 3 karbonatomer potensi-erende virkning på heksabarbital-bedøvende middel, hypothermia, ptosis og muskel-relakserende aktivitet og også anti-tetra-benazin-aktivitet. 9-formyl-9,10-dihydro-9,10-metanoantracen-forbindelsen med formel (1) fremstilles i henhold til oppfinnelsen fra 9-amino-12-hydroksy-9,10-dihydro-9,10-etanoantracenet med formel (11)
ved hjelp av omleiring.
Omleiring av aminer og a-amino-alkoholderivater ved behandling med salpetersyrling er kjent som Demjanov-omleiring og Tiffeneu-Demjanov-omleiring (Organic Reactions, bind 11, side 157, John Wiley & Sons, Inc.). Disse omleiringsreaksjoner har vært anvendt for ring-forstørrende reaksjoner i de fleste av de rapporterte eksempler, og bare et fåtall eksempler på anvendelse av omleiringsreaksjonen for ring-sammentrekkende reaksjoner har vært rapportert. Praktisk har omleiring av 9,10-etanoantracen-derivater til 9-formyl-9,10-dihydro-9,lOmetanoan-tracen ikke blitt rapportert og dette er en ny og fordelaktig fremgangsmåte for fremstilling av 9-formyl-9,10-dihydro-9,10-metanoantracen.
Omleiringen av 9-amino-12-hydroksy-9,10-dihydro-9,10-etanoantracen til 9-formyl-9,10-dihydro-9,10-metanoantracen kan gjennomføres ved behandling med salpetersyrling. Dvs. at 9-amino-12-hydroksy-9,10-dihydro-9,10-etanoantracen behandles med salpetersyrling eller metallnitrit som f.eks. natriumnitrit eller kaliumnitrit i et surt medium som f.eks. eddiksyre, maursyre, saltsyre, brom-hydrogensyre, svovelsyre eller fosforsyre eller en blanding av disse syrer. Et inert løsnings-middel som f.eks. vann,' metanol,etanol, aceton, benzen, toluen, kloroform,dikloroetan, diklorometan, dietyleter, etylenglykol-dimetyleter, tetrahydrofuran, etylacetat, dimetylsulfoksyd eller dimetylformamid eller blandinger derav kan anvendes i reaksjonssystemet. Temperaturen for behandlingen i dette til-felle kan varieres fra isavkjøling til tilbakeløpstemperaturen for reduksjonssystemet.
Det 9-formyl-9,10-dihydro-9,10-metanoantracen med formeld)
som fremstilles på denne måte kan separeres fra reaksjonsblandingen og renses ved konvensjonelle metoder.
Forbindelsen (11) (dvs. 9-amino-12-hydroksy-9,10-dihydro-9,10 etanoantracen) kan fordelaktig fremstilles fra en forbindelse med formel (111) hvori R er hydrogen eller en hydroksy1-beskyttende gruppe som f.eks. acetyl, benzoyl eller tetrahydropyranyl ved omleiring som f.eks. Curtius—reaksjonen eller Hoffman-omleiring og hydrolyse. Omleirihgen kan f.eks. gjennomføres ved den generelle fremgangsmåte for Curtius-reaksjonen (Organic Reactions, bind 3, side 337, John Wiley&Sons, Inc.), og hydrolysen kan gjennomføres under de vanlige hydrolysebetingelser for uretan eller isocyanat-derivater.
Utgangsproduktene for syntese av terapeutisk aktive 9-aminoalkyl-metanoantracenforbindelser kan fremstilles fra 9-formyl-9,10-dihydro-9,10-metanoantracen med formel (1) ved anvendelse av konvensjonelle reaksjoner som f.eks. oksydasjon, reduksjon, hydrolyse, karbonkjede-forlengende reaksjon (substitusjon, Wittig-reaksjon, Reformatsky-reaksjon, Grignard reaksjon), etc.
De følgende eksempler illustrerer oppfinnelsen.
Eksempel 1
Til en løsning av 9-amino-12-hydroksy-9,10-dihydro-9,10-etanoantracen (3,0 g) i eddiksyre (240 ml) tilsettes en løsning av natriumnitrit (6,7 g) i vann (120 ml) ved 2 - 5°C, og den resulterende blanding omrøres ved den samme temperatur i 1 time og ved 95 - 105°C i 5 timer. Reaksjonsblandingen fortynnes med vann og ekstraheres med benzen. Benzen-laget vaskes med vann, tørres over natriumsulfat og inndampes til tørrhet til å gi rå krystaller av 9-formyl-9,10-dihydro-9,10-metanoantracen (2,8 g) som ble omkrystallisert til å gi fargeløse krystaller (2,45 g). Smeltepunkt 99 - 100°C. Rensing ved omkrystallisering ga videre analytisk rent 9-formyl-9,10-dihydro-9,10-metanoantracen, smeltepunkt 102,5°C.
Eksempel 2
Til en løsning av 9-amino-12-hydroksy-9,10-dihydro-9,10-etanoantracen (50 mg) i konsentrert saltsyre (2 ml) og vann (2 ml) tilsettes en løsning av natriumnitrit (112 mg) i vann (1,0 ml)
ved 0°C. Den resulterende blanding omrøres ved 0°C i 1 time og ved romtemperatur i 5 timer. Reaksjonsblandingen fortynnes med vann og ekstraheres med benzen. Benzen-laget vaskes med vann, tørres over natfiumsulfat og inndampes til tørrhet og gir rå krystaller av 9-formyl-9,10-dihydro-9,10-metanoantracen (35 mg).
Claims (2)
1. 9 ,10-dihydro-9 ,10-metanoantr-acenderivat egnet som utgangsmaterial for fremstilling av terapeutisk aktive 9-aminoalkyl-metanoantracener,
karakterisert ved at det utgjøres av 9-formyl-, 9,10-dihydro-9,10-metanoantracen med formel 1.
2. Fremgangsmåte for fremstilling av den forbindelse som er angitt i krav 1,
karakterisert ved at 9-amino-12-hydroksy-9,10-dihydro-9,10-etanoantracen med formel 11 behandles med salpetersyrling eller metallnitrit i surt medium.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14373474A JPS5170760A (ja) | 1974-12-13 | 1974-12-13 | Metanooantorasenjudotaino shinkiseizoho |
| JP752909A JPS585182B2 (ja) | 1974-12-27 | 1974-12-27 | シンキナメタノ−アントラセンユウドウタイノ セイゾウホウ |
| JP4145275A JPS5821904B2 (ja) | 1975-04-04 | 1975-04-04 | シンキナメタノ−アントラセンユウドウタイノセイゾウホウホウ |
| JP8387175A JPS5911576B2 (ja) | 1975-07-07 | 1975-07-07 | 新規なメタノ−アントラセン誘導体の製造法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO792908L true NO792908L (no) | 1976-06-15 |
Family
ID=27453741
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO79792908A NO792908L (no) | 1974-12-13 | 1979-09-07 | 9,10-dihydro-9.10-metanoantracenderivat egnet som utgangsmaterial for fremstilling av terapeutisk aktive forbindelser, samt fremgangsmaate for fremstilling av dette derivat |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US4224344A (no) |
| AR (2) | AR212586A1 (no) |
| BE (1) | BE836599A (no) |
| CA (2) | CA1061787A (no) |
| CH (1) | CH617920A5 (no) |
| DE (1) | DE2556143A1 (no) |
| ES (3) | ES443487A1 (no) |
| FR (2) | FR2293940A1 (no) |
| GB (1) | GB1508669A (no) |
| NL (1) | NL7514601A (no) |
| NO (1) | NO792908L (no) |
| NZ (1) | NZ179530A (no) |
| SE (2) | SE429040B (no) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5512575A (en) * | 1991-08-15 | 1996-04-30 | Zeneca Limited | Methanoanthraceneyl methyl piperidinyl compounds |
| GB9216297D0 (en) * | 1991-08-15 | 1992-09-16 | Ici Plc | Therapeutic agents |
| GB9216298D0 (en) * | 1991-08-15 | 1992-09-16 | Ici Plc | Piperidine derivatives |
| GB9117639D0 (en) * | 1991-08-15 | 1991-10-02 | Ici Plc | Therapeutic compounds |
| NZ568694A (en) | 2005-11-09 | 2011-09-30 | Zalicus Inc | Method, compositions, and kits for the treatment of medical conditions |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL127069C (no) * | 1961-10-10 | |||
| US3622630A (en) * | 1968-07-03 | 1971-11-23 | Smith Kline French Lab | 10-aminoalkyl-9,10-dihydroanthracenes |
| US3708525A (en) * | 1969-11-20 | 1973-01-02 | Merck & Co Inc | Chemical compounds and processes for preparing same |
| CA987318A (en) * | 1971-02-23 | 1976-04-13 | Ciba-Geigy Ag | Amines and processes for their manufacture |
-
1975
- 1975-12-11 GB GB42689/77A patent/GB1508669A/en not_active Expired
- 1975-12-11 US US05/639,974 patent/US4224344A/en not_active Expired - Lifetime
- 1975-12-12 AR AR261582A patent/AR212586A1/es active
- 1975-12-12 DE DE19752556143 patent/DE2556143A1/de not_active Withdrawn
- 1975-12-12 NZ NZ179530A patent/NZ179530A/xx unknown
- 1975-12-12 BE BE162715A patent/BE836599A/xx not_active IP Right Cessation
- 1975-12-12 CH CH1615775A patent/CH617920A5/de not_active IP Right Cessation
- 1975-12-12 CA CA241,665A patent/CA1061787A/en not_active Expired
- 1975-12-12 FR FR7538185A patent/FR2293940A1/fr active Granted
- 1975-12-12 SE SE7514077A patent/SE429040B/xx unknown
- 1975-12-13 ES ES75443487A patent/ES443487A1/es not_active Expired
- 1975-12-15 NL NL7514601A patent/NL7514601A/xx not_active Application Discontinuation
-
1976
- 1976-06-04 FR FR7617140A patent/FR2308610A1/fr active Granted
- 1976-09-27 AR AR264868A patent/AR213412A1/es active
-
1977
- 1977-05-02 ES ES77458426A patent/ES458426A1/es not_active Expired
- 1977-05-02 ES ES77458428A patent/ES458428A1/es not_active Expired
-
1978
- 1978-04-18 CA CA301,335A patent/CA1052393A/en not_active Expired
-
1979
- 1979-08-23 SE SE7907050A patent/SE7907050L/sv not_active Application Discontinuation
- 1979-09-07 NO NO79792908A patent/NO792908L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE7514077L (sv) | 1976-06-14 |
| CA1052393A (en) | 1979-04-10 |
| CA1061787A (en) | 1979-09-04 |
| AU8741075A (en) | 1977-06-16 |
| ES458428A1 (es) | 1978-12-16 |
| NZ179530A (en) | 1978-04-28 |
| AR213412A1 (es) | 1979-01-31 |
| AR212586A1 (es) | 1978-08-15 |
| SE429040B (sv) | 1983-08-08 |
| FR2293940B1 (no) | 1981-12-04 |
| FR2308610B1 (no) | 1979-06-29 |
| ES458426A1 (es) | 1978-04-01 |
| ES443487A1 (es) | 1977-11-01 |
| GB1508669A (en) | 1978-04-26 |
| US4224344A (en) | 1980-09-23 |
| CH617920A5 (no) | 1980-06-30 |
| FR2293940A1 (fr) | 1976-07-09 |
| NL7514601A (nl) | 1976-06-15 |
| FR2308610A1 (fr) | 1976-11-19 |
| BE836599A (fr) | 1976-06-14 |
| DE2556143A1 (de) | 1976-06-16 |
| SE7907050L (sv) | 1979-08-23 |
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