NO753690L - - Google Patents
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- Publication number
- NO753690L NO753690L NO753690A NO753690A NO753690L NO 753690 L NO753690 L NO 753690L NO 753690 A NO753690 A NO 753690A NO 753690 A NO753690 A NO 753690A NO 753690 L NO753690 L NO 753690L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compounds
- stands
- group
- pyridyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- BYLPZVAKOZYZPH-UHFFFAOYSA-N imidazo[2,1-a]isoquinoline Chemical class C1=CC=C2C3=NC=CN3C=CC2=C1 BYLPZVAKOZYZPH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- CSNXUYRHPXGSJD-UHFFFAOYSA-N isoquinolin-5-ol Chemical compound N1=CC=C2C(O)=CC=CC2=C1 CSNXUYRHPXGSJD-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical class [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- -1 β-pyridine carboxylic acid methyl ester Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
Foreliggende oppfinnelse vedrorer en fremgangsmåte for fremstilling av nye imidazo(2,1-a)isochinolin-derivater med formel I The present invention relates to a process for the production of new imidazo(2,1-a)isoquinoline derivatives of formula I
hvori R står for hydrogen, fluor, klor eller metyl og R^ står for grupper med formler in which R stands for hydrogen, fluorine, chlorine or methyl and R^ stands for groups with formulas
Det særegne ved fremgangsmåten i henhold til oppfinnelsen er at forbindelser med formel II The peculiarity of the method according to the invention is that compounds of formula II
hvori R har den ovennevnte betydning, omsettes med forbindelser med formel III hvori R.j har den ovennevnte betydning og X står for klor, brom eller en gruppe -QRg?hvori R^betyr en rettkjedet alkylgruppe med 1 - h karbonatomer, med den betingelse at X står for en gruppe -OR2hvis R^betyr gruppen med formel in which R has the above-mentioned meaning, is reacted with compounds of formula III in which R.j has the above-mentioned meaning and X stands for chlorine, bromine or a group -QRg?in which R^means a straight-chain alkyl group with 1 - h carbon atoms, with the condition that X stands for a group -OR2if R^means the group of formula
og reaksjonsproduktet deretter hydrolyseres. and the reaction product is then hydrolyzed.
Fremgangsmåten kan gjennomfores som beskrevet i det folgende. The procedure can be carried out as described below.
Omsetningen mellom forbindelsene med formel III og forbindelsene med formel II skjer hensiktsmessig i et inert organisk løsnings-middel, f.eks. et hydrokarbon, som heksan eller heptan eller en eter som dietyleter eller tetrahydrofuran, og i nærvær av en inert atmosfære, f.eks. en nitrogenatmosfære. Omsetningen skjer hensikts messig ved temperaturer på - 30 til + 50°C, foretrukket - 20 til 0°G. Foretrukket anvendte forbindelser med formel III er den hvori X står for -OR2 ©g R2står for metyl eller etyl. The reaction between the compounds of formula III and the compounds of formula II conveniently takes place in an inert organic solvent, e.g. a hydrocarbon, such as hexane or heptane or an ether such as diethyl ether or tetrahydrofuran, and in the presence of an inert atmosphere, e.g. a nitrogen atmosphere. The conversion conveniently takes place at temperatures of - 30 to + 50°C, preferably - 20 to 0°G. Preferred used compounds of formula III are those in which X stands for -OR 2 and R 2 stands for methyl or ethyl.
Den etterfølgende hydrolyse av reaksjonsproduktet skjer på i og for seg kjent måte, f.eks. i vann, en fortynnet mineralsyre eller i en vanndig ammoniumkloridlosning. The subsequent hydrolysis of the reaction product takes place in a manner known per se, e.g. in water, a dilute mineral acid or in an aqueous ammonium chloride solution.
De erholdte forbindelser med formel I kan isoleres og renses påThe obtained compounds of formula I can be isolated and purified
i og for seg kjent måte. Om onsket kan de-fri baser på i©g for seg kjent måte overfores i sine syreaddisjonssalter og omvendt. in and of itself known manner. If desired, free bases can be converted in a manner known per se into their acid addition salts and vice versa.
De ved- den ovennevnte fremgangsmåte som utgangsforbindelser anvendte forbindelser med formel II kan fremstilles ved at forbindelser med formel IV The compounds of formula II used as starting compounds in the above-mentioned method can be prepared by compounds of formula IV
hvori R har den ovennevnte betydning, i et inert organisk løs-ningsmiddel og i inert gass-atmosfære omsettes med forbindelser med formel V in which R has the above-mentioned meaning, in an inert organic solvent and in an inert gas atmosphere is reacted with compounds of formula V
hvori R^står for en alkylgruppe med 1-^f karbonatomer. in which R^ stands for an alkyl group with 1-4 carbon atoms.
Fremstillingen av forbindelsene med formel II skjer hensiktsmessig under de samme betingelser som fremstillingen av•forbindelsene med formel I gjennom omsetning av forbindelser med formel II med forbindelser med formel III. En unntagelse danner den anvendte temperatur, som ved omsetningen mellom forbindelsene med formel IV og forbindelsene med formel V skal utgjore fra 25 - 75°C, spesielt fra 30 til ^-0°C. The preparation of the compounds of formula II conveniently takes place under the same conditions as the preparation of the compounds of formula I through reaction of compounds of formula II with compounds of formula III. An exception is the temperature used, which in the reaction between the compounds of formula IV and the compounds of formula V should be from 25 to 75°C, in particular from 30 to ^-0°C.
De således erholdte forbindelser med formel II kan isoleres og renses på i og for seg kjent måte. Foretrukket isoleres dog ikke forbindelsene med formel II, men anvendes videre direkte uten isolering for fremstilling av -forbindelsene med formel I. The thus obtained compounds of formula II can be isolated and purified in a manner known per se. Preferably, however, the compounds of formula II are not isolated, but are further used directly without isolation for the preparation of the compounds of formula I.
Forbindelsene med formler III og IV er enten kjén,te eller kan fremstilles på i og for seg kjent måte fra kjente utgangsforbindelser. The compounds of formulas III and IV are either known or can be prepared in a manner known per se from known starting compounds.
Forbindelsene med formel I kan likeledes opptre i deres tautomere form, som er gjengitt ved formel Ia The compounds of formula I can also appear in their tautomeric form, which is represented by formula Ia
hvori R og R^har den ovennevnte betydnig. Den form hvori for-bindelsen med formel I i sin helhet eller for den overveiende del som vedkommende befinner seg i avhenger av de aktuelle betingelser, spesielt av pH-verdien. Forbindelsene med formel I kan for den overveiende del opptre i den ved formel Ia gjengitte form, hvis forbindelsene befinner seg i form av deres syreaddisjonssalter. Selv om de ved fremgangsmåten i henhold til oppfinnelsen fremstill-bare forbindelser betegnes ved formel I og den overensstemmende wherein R and R^ have the above meaning. The form in which the compound of formula I in its entirety or for the predominant part in which it is found depends on the relevant conditions, especially on the pH value. The compounds of formula I can for the most part appear in the form represented by formula Ia, if the compounds are in the form of their acid addition salts. Although the compounds that can be produced by the method according to the invention are denoted by formula I and the corresponding
nomenklatur, er det selvfølgelig at oppfinnelsen ikke er begrenset til fremstilling av en bestemt tautomer form av disse forbindelser. nomenclature, it is of course that the invention is not limited to the preparation of a specific tautomeric form of these compounds.
Forbindelsene med formel I har en gunstig farmakodynamisk virkning. De utmerker seg spesielt ved en stimulerende virkning på sentral- nervesystemet. Dette viser seg i en av P.S.J. Spencer (Antagonism of Hypothermia in the Mouse by Anti-Depressants, in Anti-depressant drugs, sidene 19^-20^-, Eds. S. Garattini og M.N.G. Dukes, Excerpta Medica Foundation, 1967) beskrevet prove. The compounds of formula I have a favorable pharmacodynamic effect. They are particularly distinguished by a stimulating effect on the central nervous system. This is evident in one of P.S.J. Spencer (Antagonism of Hypothermia in the Mouse by Anti-Depressants, in Anti-depressant drugs, pages 19^-20^-, Eds. S. Garattini and M.N.G. Dukes, Excerpta Medica Foundation, 1967) described sample.
Forbindelsene med formel I har ut over dette en appetittdempende virkning. Den for anvendelse - som antidepressiva indikerte daglige dose bruker 50 - 300 mg som fortrinnsvis tilfores i mindre -doser på 1,5 til 150 mg-, 2 - h ganger daglig eller i retardform. For anvendelsen som appetittdemper utgjor den daglig tilforte dose fra 5 - 50 mg, som foretrukket tilfores i mindre doser på 1,5 til 25 mg 2 - h ganger daglig eller i retardform. The compounds of formula I also have an appetite-suppressing effect. The daily dose indicated for use - as an antidepressant - uses 50 - 300 mg, which is preferably administered in smaller - doses of 1.5 to 150 mg -, 2 - h times a day or in slow-release form. For use as an appetite suppressant, the daily administered dose is from 5 - 50 mg, which is preferably administered in smaller doses of 1.5 to 25 mg 2 - h times a day or in slow-release form.
Forbindelsene med formel I kan anvendes i form av de fri baser eller i form av deres farmasøytiske tålbare syreaddisjonssalter, idet saltene har den samme grad av aktivitet som de fri baser. The compounds of formula I can be used in the form of the free bases or in the form of their pharmaceutically acceptable acid addition salts, the salts having the same degree of activity as the free bases.
De syrer som er egnet for saltdannelse er spesielt uorganiske syrer som f.eks. saltsyre, eller organiske syrer som f.eks. rav-syre. The acids which are suitable for salt formation are particularly inorganic acids such as e.g. hydrochloric acid, or organic acids such as succinic acid.
For den ovennevnte anvendelse blandes forbindelsene med formelFor the above application, the compounds of formula are mixed
I hensiktsmessig med farmasøytisk tålbare fortynningsmidler eller bærestoffer og eventuelt andre tilsetninger og tilfores i form av In appropriate with pharmaceutically acceptable diluents or carriers and possibly other additives and administered in the form of
tabletter eller kapsler.tablets or capsules.
Foretrukne forbindelser med formel I er dem hvori R står for hydrogen. En ytterligere foretrukket gruppe av forbindelser er dem hvori R^betyr pyridyl. En ytterligere foretrukket gruppe er den hvori R^står for thienyl. Spesielt foretrukket er forbindelser med formel I hvori R står for hydrogen og R^står for pyridyl. Den helt spesielt foretrukket forbindelse med formel Preferred compounds of formula I are those in which R stands for hydrogen. A further preferred group of compounds are those in which R 1 is pyridyl. A further preferred group is that in which R 1 stands for thienyl. Particularly preferred are compounds of formula I in which R stands for hydrogen and R^ stands for pyridyl. The most particularly preferred compound of formula
I er 5-(<!>+-pyi'idyl)-2,3,5,6-tetrahydroimidazo(2,1-a)isochinolin-5-ol. I is 5-(<!>+-pyridyl)-2,3,5,6-tetrahydroimidazo(2,1-a)isoquinolin-5-ol.
EKSEMPEL 1 : 5-(^-pyridyl)-2,3,5,6-tetrahydromidazo EXAMPLE 1: 5-(^-pyridyl)-2,3,5,6-tetrahydromidazo
(2,1-a)isochinolin-5-ol(2,1-a)isoquinolin-5-ol
I en kolbe utstyrt med rorverk, tilbakelopskjoler, termometer og dråpetrakt tilsettes 8,0 g 2-(o-tolyl)-2(1H)-imidazolin og 200 ml vannfritt tetrahydrofuran. Blandingen gjennomspyles med nitrogen-gass og tilsettes - deretter dråpevis ved romtemperatur en losning av 105 ml (0,15 mol) n-butyllitium) av en 1,6 molar n-butyllitium-losning i heksan. Blandingen omrores deretter og oppvarmes i ca. 5 timer ved 35°C. Deretter avbrytes oppvarmingen og kolben neddykkes i et kullsyreis-acetonbad. Kolben avkjoles til den indre temperatur er falt til ca. -20°C. Deretter bringes dråpevis en losning bestående av 15g ^f-pyridin-karboksylsyre-metylester i et 100 ml vannfritt tetrahydrofuran til tildrypping med en slik hastighet at den indre temperatur ikke overstiger -20°C. Etter av-sluttet tilsetning holdes blandingen videre i ytterligere 3 timer på ca. -20°C. Deretter fjernes kullsyreisbadet, minustemperatur får stige til ca 0°C og tilsettes dråpevis 30 ml av en mettet vanndig ammoniakklosning, idet temperaturen holdes under 20°C. Deretter settes reaksjonsblandingen bort i 12 timer ved romtemperatur og inndampes deretter i vacuum. Resten tilsettes ca. 200 ml metylenklorid og deretter 100 ml vann. Den organiske fase fra-skilles og vaskes med vann, tones over vannfritt magnesiumsulfat, filtreres og inndampes i vacuum til ca. 70 ml totalvolum. Etter ca. 1 time foretas frafiltrering hvorved det erholdes et fast stoff. Dette loses deretter i et minimum av varm 95% etanol.- Losningen inndampes idet 5~(^-pyridyl)-2,3,5,6-tetrahydroimidazo(2,1-a)iso-chinolin-5-ol med smeltepunkt 162 -16<I>+<0>C. 8.0 g of 2-(o-tolyl)-2(1H)-imidazoline and 200 ml of anhydrous tetrahydrofuran are added to a flask equipped with a stirrer, reflux condenser, thermometer and dropping funnel. The mixture is purged with nitrogen gas and - then a solution of 105 ml (0.15 mol) n-butyllithium) of a 1.6 molar n-butyllithium solution in hexane is added dropwise at room temperature. The mixture is then stirred and heated for approx. 5 hours at 35°C. The heating is then interrupted and the flask is immersed in a carbonated ice-acetone bath. The flask is cooled until the internal temperature has fallen to approx. -20°C. A solution consisting of 15 g of β-pyridine carboxylic acid methyl ester in 100 ml of anhydrous tetrahydrofuran is then added drop by drop at such a rate that the internal temperature does not exceed -20°C. After the addition has been completed, the mixture is continued for a further 3 hours of approx. -20°C. The carbonated ice bath is then removed, the minus temperature is allowed to rise to about 0°C and 30 ml of a saturated aqueous ammonia solution is added dropwise, keeping the temperature below 20°C. The reaction mixture is then set aside for 12 hours at room temperature and then evaporated under vacuum. The rest is added approx. 200 ml of methylene chloride and then 100 ml of water. The organic phase is separated and washed with water, diluted over anhydrous magnesium sulfate, filtered and evaporated in vacuum to approx. 70 ml total volume. After approx. Filtration is carried out for 1 hour, whereby a solid substance is obtained. This is then dissolved in a minimum of hot 95% ethanol.- The solution is evaporated to give 5~(^-pyridyl)-2,3,5,6-tetrahydroimidazo(2,1-a)iso-quinolin-5-ol with melting point 162 -16<I>+<0>C.
EKSEMPEL 2:EXAMPLE 2:
Under anvendelse av den i eksempel 1 beskrevne fremgangsmåte,Using the method described in example 1,
men under anvendelse av egnede utgangsforbindelser i omtrent eqviva-lente mengder fremstilles folgende forbindelser med formel I: but using suitable starting compounds in roughly equivalent amounts, the following compounds of formula I are prepared:
a) 8-klor-5-(^-pyridyl)-2,3,5?6-tetrahydroimidazo-(2,1-a)iso-chinolin-5-ol, b) 8-me tyl-5- (^-pyridyl-)-2,3,5,6-tetrahydroimidazo- (2,1-a)isochino-lin-5-ol, c) ,5-(2-thienyl)-2,3,556-tetrahydroimidazo(2,1-a)-isochinolin-5-ol, med smeltepunkt 19k - 196°C, d) 5- (3-pyi'idyl)-2,3,55 6-tetrahydrolmidazo(2,1-a)-isochinolin-5-ol, med smeltepunkt 162 - 163°C, og e) 5-(2-pyridyl)-2,3,5)6-tetrahydroimidazo(2,1-a)-isochinolin-5-ol. a) 8-chloro-5-(^-pyridyl)-2,3,5?6-tetrahydroimidazo-(2,1-a)iso-quinolin-5-ol, b) 8-methyl-5-(^ -pyridyl-)-2,3,5,6-tetrahydroimidazo-(2,1-a)isoquino-lin-5-ol, c) ,5-(2-thienyl)-2,3,556-tetrahydroimidazo(2,1 -a)-isoquinolin-5-ol, with melting point 19k - 196°C, d) 5-(3-pyridyl)-2,3,55 6-tetrahydrolmidazo(2,1-a)-isoquinoline-5- ol, with melting point 162 - 163°C, and e) 5-(2-pyridyl)-2,3,5)6-tetrahydroimidazo(2,1-a)-isoquinolin-5-ol.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52314174A | 1974-11-12 | 1974-11-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO753690L true NO753690L (en) | 1976-05-13 |
Family
ID=24083820
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO753690A NO753690L (en) | 1974-11-12 | 1975-11-04 |
Country Status (13)
| Country | Link |
|---|---|
| JP (1) | JPS5170799A (en) |
| AU (1) | AU8656175A (en) |
| BE (1) | BE835446A (en) |
| DD (1) | DD122682A5 (en) |
| DE (1) | DE2549088A1 (en) |
| DK (1) | DK494275A (en) |
| ES (1) | ES442490A1 (en) |
| FI (1) | FI753070A7 (en) |
| FR (1) | FR2290901A1 (en) |
| NL (1) | NL7513061A (en) |
| NO (1) | NO753690L (en) |
| SE (1) | SE7512323L (en) |
| ZA (1) | ZA757124B (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1258946A (en) * | 1969-05-06 | 1971-12-30 | ||
| US3624093A (en) * | 1970-03-10 | 1971-11-30 | American Home Prod | 5,6-disubstituted-2,3,5,6-tetrahydroimidazo-{8 2,1-{60 {9 isoquinolin-6-ols |
| DE2460527A1 (en) * | 1974-01-02 | 1975-07-10 | Sandoz Ag | NEW ORGANIC COMPOUNDS AND PROCEDURES FOR THEIR PRODUCTION |
-
1975
- 1975-11-03 DK DK494275A patent/DK494275A/en unknown
- 1975-11-03 DE DE19752549088 patent/DE2549088A1/en active Pending
- 1975-11-03 FI FI753070A patent/FI753070A7/fi not_active Application Discontinuation
- 1975-11-04 SE SE7512323A patent/SE7512323L/en unknown
- 1975-11-04 NO NO753690A patent/NO753690L/no unknown
- 1975-11-07 NL NL7513061A patent/NL7513061A/en unknown
- 1975-11-10 JP JP50134194A patent/JPS5170799A/en active Pending
- 1975-11-10 BE BE161757A patent/BE835446A/en unknown
- 1975-11-10 ES ES442490A patent/ES442490A1/en not_active Expired
- 1975-11-11 DD DD189396A patent/DD122682A5/xx unknown
- 1975-11-12 AU AU86561/75A patent/AU8656175A/en not_active Expired
- 1975-11-12 ZA ZA757124A patent/ZA757124B/en unknown
- 1975-11-12 FR FR7534456A patent/FR2290901A1/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| ES442490A1 (en) | 1977-05-16 |
| ZA757124B (en) | 1977-06-29 |
| DD122682A5 (en) | 1976-10-20 |
| NL7513061A (en) | 1976-05-14 |
| FR2290901A1 (en) | 1976-06-11 |
| FI753070A7 (en) | 1976-05-13 |
| DE2549088A1 (en) | 1976-05-13 |
| DK494275A (en) | 1976-05-13 |
| JPS5170799A (en) | 1976-06-18 |
| AU8656175A (en) | 1977-05-19 |
| FR2290901B1 (en) | 1978-07-28 |
| BE835446A (en) | 1976-05-10 |
| SE7512323L (en) | 1976-05-13 |
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