NO144548B - Elastisk mellomledd for akselkoblinger. - Google Patents
Elastisk mellomledd for akselkoblinger. Download PDFInfo
- Publication number
- NO144548B NO144548B NO760444A NO760444A NO144548B NO 144548 B NO144548 B NO 144548B NO 760444 A NO760444 A NO 760444A NO 760444 A NO760444 A NO 760444A NO 144548 B NO144548 B NO 144548B
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- general formula
- dihydroisoquinolinium
- tetrahydroisoquinoline
- group
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- BUZYGTVTZYSBCU-UHFFFAOYSA-N 1-(4-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C=C1 BUZYGTVTZYSBCU-UHFFFAOYSA-N 0.000 claims description 4
- 150000003526 tetrahydroisoquinolines Chemical class 0.000 claims description 4
- YQYGPGKTNQNXMH-UHFFFAOYSA-N 4-nitroacetophenone Chemical compound CC(=O)C1=CC=C([N+]([O-])=O)C=C1 YQYGPGKTNQNXMH-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- WBPAOUHWPONFEQ-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C(Cl)=C1 WBPAOUHWPONFEQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims 2
- AWOUIWVQSFMVNU-UHFFFAOYSA-N 6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium Chemical class C1C[N+](C)=CC2=C1C=C(OC)C(OC)=C2 AWOUIWVQSFMVNU-UHFFFAOYSA-N 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 230000008018 melting Effects 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 7
- -1 methylenedioxy group Chemical group 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000009833 condensation Methods 0.000 description 5
- 230000005494 condensation Effects 0.000 description 5
- NKSZCPBUWGZONP-UHFFFAOYSA-N 3,4-dihydroisoquinoline Chemical class C1=CC=C2C=NCCC2=C1 NKSZCPBUWGZONP-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 2
- NSLJVQUDZCZJLK-UHFFFAOYSA-N 6,7-dimethoxy-3,4-dihydroisoquinoline Chemical compound C1CN=CC2=C1C=C(OC)C(OC)=C2 NSLJVQUDZCZJLK-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- DQYCYCFBDDBXSA-UHFFFAOYSA-M S(=O)(=O)(OC)[O-].C[N+]1=CC2=CC(=C(C=C2CC1)OC)OC Chemical compound S(=O)(=O)(OC)[O-].C[N+]1=CC2=CC(=C(C=C2CC1)OC)OC DQYCYCFBDDBXSA-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 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
- 239000002253 acid Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000005956 quaternization reaction Methods 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MBYDROYCUIVSIZ-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-(4-methoxy-6-methyl-7,8-dihydro-5h-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)ethanone Chemical compound C1=2C(OC)=C3OCOC3=CC=2CCN(C)C1CC(=O)C1=CC=C(Cl)C=C1 MBYDROYCUIVSIZ-UHFFFAOYSA-N 0.000 description 1
- PIPWSBOFSUJCCO-UHFFFAOYSA-N 2,2-dimethylpiperazine Chemical compound CC1(C)CNCCN1 PIPWSBOFSUJCCO-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
- NITZINGOACXSIR-UHFFFAOYSA-M 6,7,8-trimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium;iodide Chemical compound [I-].C1C[N+](C)=CC2=C1C=C(OC)C(OC)=C2OC NITZINGOACXSIR-UHFFFAOYSA-M 0.000 description 1
- DMOMXUSXIBJYED-UHFFFAOYSA-M 6,7-dimethoxy-2-methyl-3,4-dihydroisoquinolin-2-ium;iodide Chemical compound [I-].C1C[N+](C)=CC2=C1C=C(OC)C(OC)=C2 DMOMXUSXIBJYED-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- KIWBPDUYBMNFTB-UHFFFAOYSA-N Ethyl hydrogen sulfate Chemical compound CCOS(O)(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241001342522 Vampyrum spectrum Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- BWQAGVANIBSWBW-UHFFFAOYSA-M cotarnine chloride Chemical compound [Cl-].C1C[N+](C)=CC2=C1C=C1OCOC1=C2OC BWQAGVANIBSWBW-UHFFFAOYSA-M 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16D—COUPLINGS FOR TRANSMITTING ROTATION; CLUTCHES; BRAKES
- F16D3/00—Yielding couplings, i.e. with means permitting movement between the connected parts during the drive
- F16D3/50—Yielding couplings, i.e. with means permitting movement between the connected parts during the drive with the coupling parts connected by one or more intermediate members
- F16D3/60—Yielding couplings, i.e. with means permitting movement between the connected parts during the drive with the coupling parts connected by one or more intermediate members comprising pushing or pulling links attached to both parts
- F16D3/62—Yielding couplings, i.e. with means permitting movement between the connected parts during the drive with the coupling parts connected by one or more intermediate members comprising pushing or pulling links attached to both parts the links or their attachments being elastic
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T74/00—Machine element or mechanism
- Y10T74/21—Elements
- Y10T74/2142—Pitmans and connecting rods
- Y10T74/2144—Yieldable
Landscapes
- General Engineering & Computer Science (AREA)
- Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Springs (AREA)
- Shafts, Cranks, Connecting Bars, And Related Bearings (AREA)
- Moulding By Coating Moulds (AREA)
- Actuator (AREA)
- Joints Allowing Movement (AREA)
- Mechanical Coupling Of Light Guides (AREA)
- Snaps, Bayonet Connections, Set Pins, And Snap Rings (AREA)
- Exhaust Silencers (AREA)
- Braking Arrangements (AREA)
- Pivots And Pivotal Connections (AREA)
- Vehicle Body Suspensions (AREA)
Description
Fremgangsmåte for fremstilling av terapeutisk virksomme tetrahydroisokinolin-derivater.
Nærværende oppfinnelse vedrører en fremgangsmåte for fremstilling av terapeutisk virksomme tetrahydroisokinolinderiva-ter med den generelle formel
hvor R, er halogen, en hydroxy- eller en nitrogruppe, R2 en lavere alkylgruppe, R;1 er en lavere alkoxygruppe, henholdsvis er 2 hosliggende R.r substituenter en lavere alkylendioxygruppe, m er verdien 1, 2 eller 3, og n verdien 2 eller 3, og salt av disse forbindelser. Fremgangsmåten er karakterisert ved at man kondenserer en dihydroisokinolinium-forbindelse med den generelle formel hvor A- er et anion og R2, R8 og n har ovenfor nevnte betydning, med et keton med den generelle formel
hvor R, og m har ovenfor nevnte betydning,
i nærvær av et basisk kondensasjonsmiddel og overfører det dannede tetrahydroisokinolin-derivat, hvis ønsket, til et salt.
En foretrukken lavere alkylrest R2 er methylenresten, en foretrukken lavere alk-oxyrest er methoxyresten og en foretrukken alkylendioxygruppe er methylendioxy-gruppen. Som halogenatom er klor fore-trukket. Anionet A- i formel II er for-trinnsvis et halogenanion, som klor-, brom-, jod-anion, eller et alkylsulfat-anion som methyl- eller ethylsulfat-anion.
Dihydroisokinolinium-forbindelsene med den generelle formel II kan lett opp-nås fra de tilsvarende 3,4-dihydroisokinoliner ved behandling med et egnet kvaterni-seringsmiddel. Slike er f. eks. alkylhaloge-nid, som methyljodid, methylbromid, ethyl-jodid, eller dialkylsulfat som dimethylsulfat eller diethylsulfat.
Kvaterniseringen gjennomføres hensiktsmessig i et organisk oppløsningsmiddel som eddiksyre. En egnet utførelsesform består i at man lar 3,4-dihydroisokinoliner henstå med en ekvivalent mengde av kva-terniseringsmiddel i eddikesteroppløsning ved værelsetemperatur eller svak forhøyet temperatur. De kvaternære i 2-stilling med en alkylgruppe substituert 3,4-dihydroiso-kinoliniumforbindelser faller da som regel ut og er for det meste krystallinske stoffer som er oppløselige i vann.
De til kvaternisering anvendte 3,4-di-hydroisokinolinforbindelser er på sin side delvis kjente forbindelser, som kan frem-stilles efter kjente fremgangsmåter. En slik består f. eks. i at man omdanner et tilsvarende substituert |3-fenylethylamin til formamid, og sykliderer dette efter Bischler-Naperalski. Videre kan også alke-nylbenzol, hvis ethylenbinding står i kon-jugasjon til den aromatiske kjerne, om-setter ved imidhalogenider, eller 2-(|3-bromalkyl)-benzaldehyder bringes til reaksjon med ammoniakk eller hydroxylamin under efterfølgende reduksjon av N-oxyd.
Omsetningen ifølge oppfinnelsen fore-tas i nærvær av et basisk kondensasjonsmiddel. Slike kondensasjonsmidler er f. eks. alkalier som alkalimetallhydroxyder, f. eks. natrium- eller kaliumhydroxyd eller alkali-metallalkoholater, f. eks. natriummethylat. Også organiske baser som dimethylamin, triethylamin, piperidin, pyridin, kan an-vendes som kondensasjonsmidler. Det er hensiktsmessig å foreta reaksjoner under tilsetning av et organisk oppløsningsmid-del, f. eks. i et alkohol som methanol, etha-nol eller cyklisk eter som dioxan eller tet-rahydrofuran, eller i blanding av et slikt med vann.
En foretrukken utførelsesform består i at man bringer sammen ekvivalente mengder av forbindelsene med formlene II og III oppløst i en lavere alkohol, f. eks. methanol og tilsetter oppløsningen omtrent en ekvivalent vandig, fortynnet, f. eks. 3 n natronlut. Oppløsningen får derpå henstå flere timer ved romtemperatur. For å frem-skynde kondensasjonen, kan også arbeides ved svak, forhøyet temperatur, f. eks. inntil 50°. Efter avdampning av oppløsnings-midler opparbeides kondensasjonsmidler på vanlig måte.
Fremgangsmåteproduktene er basiske, for det meste krystallinske stoffer, som danner krystalliserbare vannoppløselige salter ved de vanlige uorganiske syrer, f. eks. svovelsyre, fosforsyre, halogenhydro-gensyrer, som saltsyre, bromhydrogensyre, og med de vanlige organiske syrer, f. eks. vinsyre, eplesyre, sitronsyre, ravsyre. Disse salter krystalliseres som regel med varie-rende mengder krystallvann.
Såvel basene med den generelle formel I såvel deres syreaddisjonssalter innehar verdifulle farmakologiske, f. eks. analge-tiske og hostestillende egenskaper og kan derfor finne anvendelse som legemiddel.
Fremgangsmåteproduktene er videre verdifulle mellomprodukter for syntesen av andre terapeutisk virksomme forbindelser.
Eksempel.
18 g 2-methyl-6,7-dimethoxy-3,4-dihydroisokinolinium-methylsulfat (smeltepunkt 157°; fremstilt fra 6,7-dimethoxy-3,4-dihydroisokinolin og dimethylsulfat i eddikester-oppløsning) og 10 g p-kloraceto-f enon oppløses i 200 ml methanol. Til denne oppløsning tilsetter man 17 ml 3n natronlut og lar henstå i 24 timer ved romtemperatur. Efter å ha vært innestengt i vann-strålevakuum, tilsettes fortynnet saltsyre inntil kongesur reaksjon og rystes ut med eter for å fjerne nøytrale deler. Den salt-sure, vandige oppløsning innstilles derpå alkalisk ved tilsetning av sodaoppløsning. Det utfallende produkt filtreres, tørkes over fosforpentoxyd ved romtemperatur og gjenoppløses derpå i eddikester-petroleter. Man får 17 g l-(p-klorfenacyl)-2-methyl-6,7-dimethoxy-l,2,3,4-tetrahydroisokinolin med smeltepunkt 106—107°. Det i aceton ved tilsetning av alkoholisk saltsyre fremstilt hydroklorid, smelter ved 151—152°. U.V.-spektret viser maksima ved 256 og 283 (Schulter) mp.; e = 18,550 og 5,860
(i etanol).
På tilsvarende måte ble fremstilt: Fra 2-methyl-6,7-dimethoxy-3,4-dihydroisokinolinium-jodid (smeltepunkt 210— 211°) og p-nitroacetophenon: l-(p-nitrof enacyl)-2-methyl-6,7-dimeth-oxy-1,2,3,4-tetrahy dr oisokinolin. Smelte - punkt for basen 120°, smeltepunkt for hydroklorid: 173—174°. Fra 2-methyl-6,7,8-trimethoxy-3,4-dihydroisokinolinium-jodid (smeltepunkt 184 —185°) og p-kloracetophenon: 1- (p-klorf enacyl) -2-methyl-6,7,8-trimeth-oxy-l,2,3,4-tetrahydroisokinolin. Smeltepunkt for hydroklorid: 120—121°.
Fra 2-methyl-6,7-methylendioxy-8-methoxy-3,4-dihydroisokinolinium-klorid (cotarninklorid) og p-nitroacetophenon: l-(p-nitrof enacyl) -2-methyl-6,7-methylen-dioxy-8-methoxy-l,2,3,4-tetrahydroisokinolin med smeltepunkt 155—156°.
Fra 2-methyll-6,7-methy]lendioxy-8-methoxy-3,4-dihydroisokinolinium-klorid og p-kloracetophenon: 1- (p-klorf enacyl) -2-methyl-6,7-methy-lendioxy- 8-methoxy -1,2,3,4-tetrahy dro - isokinolin med smeltepunkt 113°; Smeltepunkt for hydroklorid: 184°.
Fra 2-methyl-6,7-dimethoxy-3,4-dihydroisokinolinium-methylsulfat og 3,4-dikloracetophenon: 1- (3,4-diklorf enacyl) -2-methyl-6,7-di-methoxy-l,2,3,4-tetrahydroisokinolin med
smeltepunkt 147—149°.
Fra 2-methyl-6,7-dimethoxy-3,4-di-hydroisokinblinium-methylsulfat og p-hydroxyacetophenon: 1-(p-hydroxyf enacyl)-2-methyl-6,7-di-methoxy-1,2,3,4-tetrahydroisokinolin med
smeltepunkt 147—148°.
Claims (2)
1. Fremgangsmåte for fremstilling av terapeutisk virksomme tetrahydroisokino-linderviater med den generelle formel
hvor R, er halogen, en hydroxy- eller nitrogruppe, R2 en lavere alkylgruppe, R3 er en lavere alkoxygruppe, henholdsvis er to hosliggende R3-substituenter en lavere alkylendioxygruppe, m er verdien 1, 2 eller 3 og n verdien 2 eller 3,
og av salter av disse forbindelser, karakterisert ved at man kondenserer en dihydroisokinolinium-forbindelse med den generelle formel
hvor R2, R3 og n har ovenfor angitte betydning og A— er et anion, med et keton med den generelle formel
hvor R1 og m har ovenfor angitte betydning,
i nærvær av et basisk kondensasjonsmiddel, og overfører det dannede tetrahydroisokinolin-derivat, hvis ønsket, til et salt.
2. Fremgangsmåte efter påstand 1, karakterisert ved at man kondenserer et 2-methyl-6,7-dimethoxy-3,4-di-hydroisokinoliniumsalt med p-kloraceto-fenon, 3,4-dikloracetofenon eller p-nitro-acetofenon.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2510197A DE2510197C3 (de) | 1975-03-08 | 1975-03-08 | Elastisches Zwischenglied für Wellenkupplungen |
| DE19752516238 DE2516238B2 (de) | 1975-04-14 | 1975-04-14 | Zwischenglied fur elastische Kupplungen |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO760444L NO760444L (no) | 1976-09-09 |
| NO144548B true NO144548B (no) | 1981-06-09 |
| NO144548C NO144548C (no) | 1981-09-16 |
Family
ID=25768603
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO760444A NO144548C (no) | 1975-03-08 | 1976-02-12 | Elastisk mellomledd for akselkoblinger. |
| NO803733A NO144579C (no) | 1975-03-08 | 1980-12-11 | Mellomledd for elastiske koblinger. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO803733A NO144579C (no) | 1975-03-08 | 1980-12-11 | Mellomledd for elastiske koblinger. |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US4031714A (no) |
| JP (1) | JPS5840053B2 (no) |
| AR (1) | AR211334A1 (no) |
| AT (1) | AT363738B (no) |
| BR (1) | BR7601367A (no) |
| CA (1) | CA1025227A (no) |
| CS (1) | CS205017B2 (no) |
| DD (1) | DD123220A5 (no) |
| DK (1) | DK152941C (no) |
| ES (1) | ES445051A1 (no) |
| FI (1) | FI65653C (no) |
| FR (1) | FR2303990A1 (no) |
| GB (1) | GB1533883A (no) |
| IT (1) | IT1056932B (no) |
| NL (1) | NL180452C (no) |
| NO (2) | NO144548C (no) |
| PL (1) | PL121002B1 (no) |
| PT (1) | PT64858B (no) |
| SE (1) | SE417746B (no) |
| YU (1) | YU39171B (no) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2734279A1 (de) * | 1977-07-29 | 1979-02-08 | Hackforth Gmbh & Co Kg | Elastische wellenkupplung |
| GB8502838D0 (en) * | 1985-02-05 | 1985-03-06 | Flexibox Ltd | Centrifugal couplings |
| US5954552A (en) * | 1998-03-13 | 1999-09-21 | Lauterbach; Joachim | Combined clutch and torsion damper for water jet propulsion |
| AU773599B2 (en) * | 1999-08-11 | 2004-05-27 | Joachim Lauterbach | Combined clutch and torsion damper for water jet propulsion |
| DE10112260C1 (de) * | 2001-03-14 | 2003-01-16 | Sgf Gmbh & Co Kg | Drehelastische Wellenkupplung |
| CN101495769A (zh) * | 2006-06-27 | 2009-07-29 | 洛德公司 | 多级扭转联轴器 |
| DE102011012922A1 (de) * | 2011-03-03 | 2012-09-06 | SGF SüDDEUTSCHE GELENKSCHEIBENFABRIK GMBH & CO. KG | Verfahren zum Herstellen eines elastischen Kraftübertragungsglieds und elastisches Kraftübertragungsglied |
| DE102011013332A1 (de) * | 2011-03-08 | 2012-09-13 | SFG Süddeutsche Gelenkscheibenfabrik | Elastischer Gelenkkörper |
| DE102011119936A1 (de) * | 2011-12-01 | 2013-06-06 | SGF SüDDEUTSCHE GELENKSCHEIBENFABRIK GMBH & CO. KG | Elastisches Kraftübertragungsglied und Kupplungsvorrichtung |
| DE202013008117U1 (de) | 2013-09-12 | 2013-09-24 | SGF SüDDEUTSCHE GELENKSCHEIBENFABRIK GMBH & CO. KG | Elastischer Gelenkkörper |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1759356A (en) * | 1926-03-09 | 1930-05-20 | Kattwinkel Hans | Power-transmitting means |
| GB321999A (en) * | 1928-08-29 | 1929-11-28 | Christian Hamilton Gray | Improvements in or relating to universal joints |
| US2073852A (en) * | 1935-05-31 | 1937-03-16 | Caterpillar Tractor Co | Drive connecting link |
| FR837975A (fr) * | 1937-05-19 | 1939-02-23 | Perfectionnements apportés aux joints flexibles ou élastiques notamment pour des arbres de transmission | |
| DE814364C (de) * | 1949-01-16 | 1951-09-20 | Adam Pleines | Gelenkscheibe, insbesondere fuer Kraftfahrzeugwellen, aus Gummi mit Verstaerkungseinlagen |
| GB696719A (en) * | 1950-07-07 | 1953-09-09 | Pirelli | Improvements relating to flexible transmission couplings |
| CH303013A (de) * | 1952-04-24 | 1954-11-15 | Jordi Gottfried Otto | Elastische Kupplung. |
| DE1040854B (de) * | 1953-02-24 | 1958-10-09 | Eduard Erhardt Fa | Elastische Wellengelenkscheibe |
| DE1041309B (de) * | 1955-11-15 | 1958-10-16 | Daimler Benz Ag | Elastische Kupplungsscheibe |
| US3362252A (en) * | 1965-10-21 | 1968-01-09 | Bendix Corp | Redundant connecting link |
-
1976
- 1976-01-28 AT AT0058476A patent/AT363738B/de not_active IP Right Cessation
- 1976-02-10 ES ES445051A patent/ES445051A1/es not_active Expired
- 1976-02-11 SE SE7601477A patent/SE417746B/xx not_active IP Right Cessation
- 1976-02-12 NO NO760444A patent/NO144548C/no unknown
- 1976-02-17 FR FR7604534A patent/FR2303990A1/fr active Granted
- 1976-02-17 GB GB6257/76A patent/GB1533883A/en not_active Expired
- 1976-02-19 YU YU00419/76A patent/YU39171B/xx unknown
- 1976-02-23 DK DK073876A patent/DK152941C/da not_active IP Right Cessation
- 1976-02-23 AR AR262341A patent/AR211334A1/es active
- 1976-02-24 US US05/661,451 patent/US4031714A/en not_active Expired - Lifetime
- 1976-02-25 FI FI760496A patent/FI65653C/fi not_active IP Right Cessation
- 1976-02-27 DD DD191598A patent/DD123220A5/xx unknown
- 1976-03-01 PT PT64858A patent/PT64858B/pt unknown
- 1976-03-03 PL PL1976187676A patent/PL121002B1/pl unknown
- 1976-03-04 CS CS761334A patent/CS205017B2/cs unknown
- 1976-03-05 BR BR7601367A patent/BR7601367A/pt unknown
- 1976-03-05 CA CA247,233A patent/CA1025227A/en not_active Expired
- 1976-03-08 JP JP51024958A patent/JPS5840053B2/ja not_active Expired
- 1976-03-08 NL NLAANVRAGE7602428,A patent/NL180452C/xx not_active IP Right Cessation
- 1976-03-08 IT IT20945/76A patent/IT1056932B/it active
-
1980
- 1980-12-11 NO NO803733A patent/NO144579C/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK152941C (da) | 1988-10-17 |
| FI65653B (fi) | 1984-02-29 |
| NO760444L (no) | 1976-09-09 |
| FI65653C (fi) | 1984-06-11 |
| SE7601477L (sv) | 1976-09-09 |
| FI760496A (no) | 1976-09-09 |
| AR211334A1 (es) | 1977-11-30 |
| FR2303990A1 (fr) | 1976-10-08 |
| DD123220A5 (no) | 1976-12-05 |
| JPS51143159A (en) | 1976-12-09 |
| NO144579C (no) | 1981-09-23 |
| US4031714A (en) | 1977-06-28 |
| DK73876A (da) | 1976-09-09 |
| NO803733L (no) | 1976-09-09 |
| IT1056932B (it) | 1982-02-20 |
| NL180452C (nl) | 1987-02-16 |
| CS205017B2 (en) | 1981-04-30 |
| AT363738B (de) | 1981-08-25 |
| CA1025227A (en) | 1978-01-31 |
| NO144579B (no) | 1981-06-15 |
| NL7602428A (nl) | 1976-09-10 |
| DK152941B (da) | 1988-05-30 |
| BR7601367A (pt) | 1976-09-14 |
| PL121002B1 (en) | 1982-04-30 |
| FR2303990B3 (no) | 1978-11-10 |
| GB1533883A (en) | 1978-11-29 |
| JPS5840053B2 (ja) | 1983-09-02 |
| PT64858B (de) | 1977-07-20 |
| SE417746B (sv) | 1981-04-06 |
| YU39171B (en) | 1984-08-31 |
| YU41976A (en) | 1982-05-31 |
| NL180452B (nl) | 1986-09-16 |
| PT64858A (de) | 1976-04-01 |
| ES445051A1 (es) | 1977-08-01 |
| NO144548C (no) | 1981-09-16 |
| ATA58476A (de) | 1981-01-15 |
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