NO115026B - - Google Patents
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- Publication number
- NO115026B NO115026B NO16493765A NO16493765A NO115026B NO 115026 B NO115026 B NO 115026B NO 16493765 A NO16493765 A NO 16493765A NO 16493765 A NO16493765 A NO 16493765A NO 115026 B NO115026 B NO 115026B
- Authority
- NO
- Norway
- Prior art keywords
- cyclohepta
- benzo
- dihydro
- general formula
- thiophene
- Prior art date
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- 150000003839 salts Chemical class 0.000 claims description 8
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- JWZOUYNYLGHDKZ-UHFFFAOYSA-N 5,10-dihydro-4h-benzo[1,2]cyclohepta[3,4-b]thiophene Chemical class C1CC2=CC=CC=C2CC2=C1SC=C2 JWZOUYNYLGHDKZ-UHFFFAOYSA-N 0.000 claims description 5
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910000043 hydrogen iodide Inorganic materials 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- LHARTHCFXKDMSZ-UHFFFAOYSA-N CN(CCCC1(C2=C(CCC=3SC=CC31)C=CC=C2)O)C Chemical compound CN(CCCC1(C2=C(CCC=3SC=CC31)C=CC=C2)O)C LHARTHCFXKDMSZ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 206010029333 Neurosis Diseases 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229940071870 hydroiodic acid Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 208000015238 neurotic disease Diseases 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- BQYAIXRTUQAHCK-UHFFFAOYSA-N 2h-benzo[1,2]cyclohepta[3,6-b]thiophene Chemical compound C1=C2C=CC=CC2=CC2=CCSC2=C1 BQYAIXRTUQAHCK-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- NTGDRLLWKDTZRA-UHFFFAOYSA-N CN(CCCC1C2=C(CCC=3SC=CC31)C=CC=C2)C Chemical compound CN(CCCC1C2=C(CCC=3SC=CC31)C=CC=C2)C NTGDRLLWKDTZRA-UHFFFAOYSA-N 0.000 description 1
- 235000007129 Cuminum cyminum Nutrition 0.000 description 1
- 244000304337 Cuminum cyminum Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000012545 Psychophysiologic disease Diseases 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 239000010495 camellia oil Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical class OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000004701 malic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 150000002692 maltoses Chemical class 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-M oxalate(1-) Chemical compound OC(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-M 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
- C07D333/80—Seven-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
Fremgangsmåte for fremstilling av nye, terapeutisk aktive 9,10-dihydro-4H-benzo [4,5] cyklohepta [1,2-b] tiofen-derivater. Process for the preparation of new, therapeutically active 9,10-dihydro-4H-benzo [4,5] cyclohepta [1,2-b] thiophene derivatives.
Foreliggende oppfinnelse angår en fremgangsmåte for fremstilling av nye, terapeutisk The present invention relates to a method for the production of new therapeutic agents
aktive 9,10-dihydro-4H-benzo[4,5]cyklohepta-[l,2-b]tiofen-derivater med den alminnelige formel I active 9,10-dihydro-4H-benzo[4,5]cyclohepta-[1,2-b]thiophene derivatives of the general formula I
og deres syreaddisjonssalter, hvori R3og R4hver and their acid addition salts, wherein R 3 and R 4 each
betyr en lavere alkylgruppe eller R3og R4betyr means a lower alkyl group or R 3 and R 4 mean
sammen med nitrogenatomet en pyrrolidin- eller together with the nitrogen atom a pyrrolidine or
piperidingruppe.piperidine group.
I henhold til oppfinnelsen fremstilles de nye forbindelser med den alminnelige formel I og deres syreaddisjonssalter ved at et 9,10-dihydro-4H-benzo- [4,5] cyklohepta [ 1,2-b] tiof en-derivat med den alminnelige formel II According to the invention, the new compounds with the general formula I and their acid addition salts are prepared by a 9,10-dihydro-4H-benzo-[4,5]cyclohepta[1,2-b]thiophene derivative with the general formula II
hvori R3og R4har den ovennevnte betydning, reduseres under oppvarming med jodhydrogen og rødt fosfor, og reduksjonsproduktet overføres deretter eventuelt ved behandling med uorga- in which R3 and R4 have the above-mentioned meaning, is reduced under heating with hydrogen iodide and red phosphorus, and the reduction product is then transferred, if necessary, by treatment with inorganic
niske eller organiske syrer i sine syreaddisjons-nic or organic acids in their acid addition
salter.salts.
Fremgangsmåten i henhold til oppfinnelsenThe method according to the invention
kan med fordel utføres ved at oppløsningen av en forbindelse med den alminnelige formel II, can advantageously be carried out by the dissolution of a compound of the general formula II,
som f. eks. 4-hydroksy-4-(3-dimetylaminopropyl)-9,10-dihydro-4H-benzo[4,5]-cyklohepta[l,2-b]tiofen oppvarmes i iseddik i 10—15 min. ved 120°C med rødt fosfor og jodhydrogensyre. Etter filtrering av reaksjonsblandingen og inndamp- like for example. 4-Hydroxy-4-(3-dimethylaminopropyl)-9,10-dihydro-4H-benzo[4,5]-cyclohepta[1,2-b]thiophene is heated in glacial acetic acid for 10-15 min. at 120°C with red phosphorus and hydroiodic acid. After filtering the reaction mixture and evaporating
ing av filtratet opptas resten i nærvær av alka-ing of the filtrate, the residue is taken up in the presence of alka-
lier, f. eks. 20 pst. natronlut, i et organisk opp-løsningsmiddel, fortrinnsvis metylenklorid. Fra den organiske fase fjernes jod ved hjelp av na-triumtiosulfat, og det ønskede sluttprodukt iso- scythe, e.g. 20 percent caustic soda in an organic solvent, preferably methylene chloride. Iodine is removed from the organic phase using sodium thiosulphate, and the desired end product iso-
leres på kjent måte og renses fortrinnsvis ved overføring i et egnet salt. is prepared in a known manner and preferably purified by transfer in a suitable salt.
Foretrukne salter er f. eks. hydrokloridene, hydrobromidene, fosfatene, sulfatene, acetatene, malonatene, fumaratene, malemåtene, tartrate- Preferred salts are e.g. the hydrochlorides, hydrobromides, phosphates, sulfates, acetates, malonates, fumarates, maltoses, tartrates
ne, malatene, heksahydrobenzoatene, benzensul-fonatene eller p-toluensulfonatene. ne, the malates, the hexahydrobenzoates, the benzene sulphonates or the p-toluene sulphonates.
Fra Angew. Chem. 75 s. 524—538 (1963) erFrom Angew. Chem. 75 pp. 524-538 (1963) is
det kjent en forbindelse som bare avviker fra de foreliggende forbindelser ved strukturen i side-kjeden. Den nevnte forbindelse har imidlertid en helt annen virkning enn de foreliggende, idet det dreier seg om en forbindelse med histamin-hemmende egenskaper for behandling av migre- a compound is known which only differs from the existing compounds in the structure of the side chain. The aforementioned compound, however, has a completely different effect to the present ones, as it is a compound with histamine-inhibiting properties for the treatment of migraine
ne og allergiske lidelser. I motsetning hertil er de foreliggende forbindelser, som mer utførlig omhandlet i det følgende, spesifikke antidepres- ne and allergic disorders. In contrast, the present compounds, as discussed in more detail below, are specific antidepressants
siva for behandling av nevrotiske og psykotiske forstyrrelser. siva for the treatment of neurotic and psychotic disorders.
De nye forbindelser med formel I har så-The new compounds of formula I have so-
ledes verdifulle farmakodynamiske egenskaper. Således utmerker de seg ved sterke, for anti-depressiva typiske virkninger, som ved dyrefor- led valuable pharmacodynamic properties. Thus, they are characterized by strong, for antidepressants typical effects, as in animal
søk blant annet ytrer vegetative og motoriske symptomer. Forbindelsene potensierer noradre-nalinvirkningen og besitter overveiende sentralt rettede antikolinergiske effekter. De sedativ/ nevroleptiske egenskaper er ved substansene bare måtelig utviklet. Den antidepressive virkning er altså forsåvidt spesifikk, da de dempende egen- search for, among other things, vegetative and motor symptoms. The compounds potentiate the noradrenaline effect and have mainly centrally directed anticholinergic effects. The sedative/neuroleptic properties of the substances are only moderately developed. The antidepressant effect is therefore certainly specific, as the dampening properties
skaper ved forbindelsene trer tidligere tilbake. Toksisiteten av fremgangsmåteproduktene er forholdsvis liten. creates at the connections earlier retreats. The toxicity of the process products is relatively small.
De nye forbindelser kan derfor med fordel anvendes for behandling av nevrotiske og psykotiske forstyrrelser, fremfor alt innenfor det depressive typeområde, likeledes kan de anvendes for terapi av psykosomatiske forstyrrelser. De administreres fortrinnsvis i form av deres fy-siologisk tålbare, vannoppløselige salter. The new compounds can therefore advantageously be used for the treatment of neurotic and psychotic disorders, above all within the depressive type area, they can also be used for the therapy of psychosomatic disorders. They are preferably administered in the form of their physiologically tolerable, water-soluble salts.
Forbindelsene kan anvendes som legemiddelThe compounds can be used as medicine
i seg selv eller i tilsvarende legemiddelstoffer for enteral eller parenteral administrering. For fremstilling av egnede legemiddelformer for-arbeides forbindelsene med uorganiske eller organiske, farmakologisk indifferente hjelpestoffer. Som hjelpestoffer anvendes f. eks. for by itself or in corresponding medicinal substances for enteral or parenteral administration. For the production of suitable medicinal forms, the compounds are prepared with inorganic or organic, pharmacologically indifferent excipients. As excipients, e.g. for
tabletter og dragéer melkesukker, stivelse, tal-tablets and dragées milk sugar, starch, tal-
kum, stearinsyre etc. For injeksjonspreparater anvendes f. eks.: vann, alkoholer, glycerol, plan- cumin, stearic acid, etc. For injection preparations, e.g. water, alcohols, glycerol, plan-
teoljer etc. For suppositorier anvendes f. eks.: naturlige eller herdete oljer og voksarter etc. tea oils, etc. For suppositories, for example: natural or hardened oils and waxes, etc. are used.
Videre kan preparatene inneholde egnede kon-serverings-, fuktemidler, løsningsformidlere, søtnings- og fargestoffer, aromabestanddeler etc. Furthermore, the preparations may contain suitable preservatives, wetting agents, solubilizers, sweeteners and colourings, aroma components etc.
I de etterfølgende eksempler, som skal illu-In the following examples, which shall illus-
strere utførelsen av fremgangsmåten, er alle temperaturangivelser i °C som ikke er korrigert. strer the execution of the procedure, all temperature indications are in °C which have not been corrected.
Eksempel 1.Example 1.
4- (3-dimetylaminopropyl) -9,10-dihydro-4H-benzo [4,5] cyklohepta [ 1,2-b] tiof en. 4-(3-dimethylaminopropyl)-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene.
Oppløsningen av 12,0 g 4-hydroksy-4-(3-dimetylaminopropyl)-9,10-dihydro-4H-benzo-[4,5]cyklohepta-[l,2-b]tiofen i 180 ccm iseddik tilsettes 12,0 g rødt fosfor og 64 ccm 56 pst. hyd-rogensyre, og blandingen oppvarmes under om- The solution of 12.0 g of 4-hydroxy-4-(3-dimethylaminopropyl)-9,10-dihydro-4H-benzo-[4,5]cyclohepta-[1,2-b]thiophene in 180 ccm of glacial acetic acid is added 12, 0 g of red phosphorus and 64 ccm of 56 per cent hydrogen acid, and the mixture is heated under re-
røring i 15 min. ved 120° C. Deretter filtreres reaksjonsblandingen og filtratet inndampes un- stirring for 15 min. at 120° C. The reaction mixture is then filtered and the filtrate is evaporated to
der redusert trykk. Den oljeaktige rest oppløses i 20 pst. natronlut og i metylenklorid, den organiske fase fraskilles og den vandige del ek-straheres ennå to ganger med metylenklorid. De forente metylenklorid-ekstrakter vaskes to ganger med vann, tørres over kaliumkarbonat og inndampes under redusert trykk. Oppløsnin- where reduced pressure. The oily residue is dissolved in 20% caustic soda and in methylene chloride, the organic phase is separated and the aqueous part is extracted twice more with methylene chloride. The combined methylene chloride extracts are washed twice with water, dried over potassium carbonate and evaporated under reduced pressure. Solution-
gen av resten i 35 ccm aceton tilsettes deretter den beregnede mengde hydrogenklorid i aceton og oppløsningen får langsomt avkjøles til rom-temperatur. Det utfelte hydroklorid frafiltreres og krystalliseres fra aceton. Smeltepunkt 158,5— of the residue in 35 cc of acetone, the calculated amount of hydrogen chloride in acetone is then added and the solution is allowed to cool slowly to room temperature. The precipitated hydrochloride is filtered off and crystallized from acetone. Melting point 158.5—
160° C. 160°C.
Eksempel 2.Example 2.
4- (3-piperidin-propyl) -9,10-dihydro-4H-4-(3-piperidine-propyl)-9,10-dihydro-4H-
benzo [4,5] cyklohepta [ 1,2-b] tiof en.benzo[4,5]cyclohepta[1,2-b]thiophene.
Analogt eksempel 1 fås fra 1,0 og 4-hydrok-sy-4-(3-piperidin-propyl-9,10-dihydro-4H-benzo[4,5]cyklohepta[l,2-b]tiofen, 0,75 g rødt fosfor, 5,6 ccm 56 pst. jodhydrogensyre og 16 ccm iseddik ved oppvarming i 10 min. den ønskede forbindelse. Hydrogenoksalatet smelter etter omkrystallisering fra etanol/metanol ved 195— Analogous example 1 is obtained from 1,0 and 4-hydroxy-sy-4-(3-piperidine-propyl-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene, 0, 75 g of red phosphorus, 5.6 ccm of 56% hydroiodic acid and 16 ccm of glacial acetic acid on heating for 10 min. the desired compound. The hydrogen oxalate melts after recrystallization from ethanol/methanol at 195—
196,5° C (spalting). 196.5° C (decomposition).
Claims (1)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1046764A CH444185A (en) | 1964-08-11 | 1964-08-11 | Process for the preparation of new thiophene derivatives |
| CH1046864A CH444186A (en) | 1964-08-11 | 1964-08-11 | Process for the preparation of new thiophene derivatives |
| CH806265 | 1965-06-09 | ||
| CH806365A CH473823A (en) | 1964-08-11 | 1965-06-09 | Process for the preparation of new 4H-Benzo (4,5) cyclohepta (1,2-b) thiophene derivatives |
| CH806465A CH473139A (en) | 1965-06-09 | 1965-06-09 | Process for the preparation of new 9,10-dihydro-4H-benzo (4,5) cyclohepta (1,2-b) thiophene derivatives |
| CH1519265 | 1965-11-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO115026B true NO115026B (en) | 1968-07-08 |
Family
ID=27543810
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO16493765A NO115026B (en) | 1964-08-11 | 1965-08-09 | |
| NO15927765A NO115025B (en) | 1964-08-11 | 1965-08-09 | |
| NO16493865A NO115027B (en) | 1964-08-11 | 1965-08-09 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO15927765A NO115025B (en) | 1964-08-11 | 1965-08-09 | |
| NO16493865A NO115027B (en) | 1964-08-11 | 1965-08-09 |
Country Status (8)
| Country | Link |
|---|---|
| BE (1) | BE668053A (en) |
| CH (1) | CH473823A (en) |
| DE (1) | DE1250449B (en) |
| FR (1) | FR4866M (en) |
| GB (1) | GB1112601A (en) |
| NL (1) | NL6510328A (en) |
| NO (3) | NO115026B (en) |
| SE (3) | SE326453B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8530245D0 (en) * | 1985-12-09 | 1986-01-22 | Sandoz Ltd | Organic compounds |
-
1965
- 1965-06-09 CH CH806365A patent/CH473823A/en unknown
- 1965-08-02 GB GB32955/65A patent/GB1112601A/en not_active Expired
- 1965-08-06 DE DE1965S0098688 patent/DE1250449B/en active Pending
- 1965-08-09 NO NO16493765A patent/NO115026B/no unknown
- 1965-08-09 NO NO15927765A patent/NO115025B/no unknown
- 1965-08-09 BE BE668053D patent/BE668053A/xx unknown
- 1965-08-09 NO NO16493865A patent/NO115027B/no unknown
- 1965-08-09 NL NL6510328A patent/NL6510328A/xx unknown
- 1965-08-10 SE SE10447/65A patent/SE326453B/xx unknown
- 1965-08-10 SE SE10449/65A patent/SE326454B/xx unknown
- 1965-08-10 SE SE10448/65A patent/SE326197B/xx unknown
- 1965-11-09 FR FR37801A patent/FR4866M/fr not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| SE326197B (en) | 1970-07-20 |
| CH473823A (en) | 1969-06-15 |
| SE326454B (en) | 1970-07-27 |
| SE326453B (en) | 1970-07-27 |
| NO115027B (en) | 1968-07-08 |
| NL6510328A (en) | 1966-02-14 |
| NO115025B (en) | 1968-07-08 |
| GB1112601A (en) | 1968-05-08 |
| DE1250449B (en) | 1967-09-21 |
| FR4866M (en) | 1967-02-27 |
| BE668053A (en) | 1966-02-09 |
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