NO129042B - - Google Patents
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- NO129042B NO129042B NO294470A NO294470A NO129042B NO 129042 B NO129042 B NO 129042B NO 294470 A NO294470 A NO 294470A NO 294470 A NO294470 A NO 294470A NO 129042 B NO129042 B NO 129042B
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- compound
- general formula
- defined above
- yloxy
- formula
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- 150000001875 compounds Chemical class 0.000 claims description 23
- 150000001412 amines Chemical class 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 125000000468 ketone group Chemical group 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 239000002904 solvent Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 229940039009 isoproterenol Drugs 0.000 description 4
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- 230000000747 cardiac effect Effects 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
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N sodium methoxide Substances [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 2
- BNRANURXPKRRKP-UHFFFAOYSA-N 1-[tert-butyl-[(4-methylphenyl)methyl]amino]-3-(1H-indol-4-yloxy)propan-2-ol Chemical compound Cc1ccc(CN(CC(O)COc2cccc3[nH]ccc23)C(C)(C)C)cc1 BNRANURXPKRRKP-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 230000003288 anthiarrhythmic effect Effects 0.000 description 2
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960003712 propranolol Drugs 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QWXUJPJVNKCDKJ-UHFFFAOYSA-N 1-(tert-butylamino)-3-chloropropan-2-ol;hydrochloride Chemical compound Cl.CC(C)(C)NCC(O)CCl QWXUJPJVNKCDKJ-UHFFFAOYSA-N 0.000 description 1
- -1 3-amino-2-hydroxy-propoxy group Chemical group 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010067598 Neurogenic hypertension Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002959 anti-hypotensive effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910001626 barium chloride Inorganic materials 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/22—Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
hvor R betegner en rett eller forgrenet alkylgruppe med 1-4 karbonatomer, where R denotes a straight or branched alkyl group with 1-4 carbon atoms,
eller et farmakologisk aksepterbart syreaddisjonssalt av denne. or a pharmacologically acceptable acid addition salt thereof.
3-amino-2-hydroksy-propoksygruppen ér foretrukket i 5-stilling. The 3-amino-2-hydroxy-propoxy group is preferred in the 5-position.
Eksempler på egnede salter er de av både uorganiske (f.eks. saltsyre) og organiske (f.eks. fumarsyre og sitronsyre) syrer. Examples of suitable salts are those of both inorganic (eg hydrochloric acid) and organic (eg fumaric and citric) acids.
Aminene fremstilles ved fremgangsmåter som består i The amines are produced by methods that consist of
a) å omsette en forbindelse av formel (II) eller a) to react a compound of formula (II) or
(III) (III)
hvor X er et halogenatom, where X is a halogen atom,
med et amin av den generelle formel I^NR, hvor R er som foran definert, eller with an amine of the general formula I^NR, where R is as defined above, or
b) omsette forbindelsen av formel (IV) b) reacting the compound of formula (IV)
med en forbindelse av den generelle formel (V) with a compound of the general formula (V)
XCH2CH(OH)CH2NHR (V) XCH2CH(OH)CH2NHR (V)
hvor X og R er som foran definert, eller where X and R are as defined above, or
c) omsette en forbindelse av den generelle formel (VI) c) reacting a compound of the general formula (VI)
hvor X er et halogenatom, where X is a halogen atom,
med et amin med den generelle formel I^NR, hvor R er som foran definert, hvoretter ketogruppen reduseres med et egnet reduksjonsmiddel, with an amine of the general formula I^NR, where R is as defined above, after which the keto group is reduced with a suitable reducing agent,
hvoretter den således fremstilte forbindelse av den generelle formel (I), om onsket, omdannes til salter med enten organiske eller uorganiske syrer som er terapeutisk aksepterbare. after which the thus prepared compound of the general formula (I) is, if desired, converted into salts with either organic or inorganic acids which are therapeutically acceptable.
Reaksjon a) kan utfores eventuelt i nærvær av et opplosnings-middel, f.eks. toluen eller dioksan. Reaction a) can optionally be carried out in the presence of a solvent, e.g. toluene or dioxane.
Forbindelsene av den generelle formel (III) kan fremstilles ved å omsette forbindelsen av formel (IV) med en forbindelse av den generelle formel (VII). The compounds of the general formula (III) can be prepared by reacting the compound of the formula (IV) with a compound of the general formula (VII).
hvor X er som definert foran. where X is as defined above.
Forbindelsen med formel (II) kan oppnås fra forbindelsen med den generelle formel (III) ved behandling med en base, f.eks. natriumhydroksyd, -bikarbonat eller -metoksyd. The compound of formula (II) can be obtained from the compound of general formula (III) by treatment with a base, e.g. sodium hydroxide, bicarbonate or methoxide.
Forbindelsene med den generelle formel (I) ble undersokt på deres virkning på det kardiovaskulære system og særlig på aktiviteten av p-adrenergiske reseptorer. The compounds of the general formula (I) were examined for their effect on the cardiovascular system and in particular on the activity of β-adrenergic receptors.
Det folgende ble studert: The following were studied:
(1) Deres virkning i å antagonisere den systemiske og kardio-hemodynamiske respons indusert ved injeksjon av isoproterenol (som stimulerer (3-adr energi ske reseptorer) hos katter (1) Their action in antagonizing the systemic and cardio-haemodynamic response induced by injection of isoproterenol (which stimulates (3-adrenergic receptors) in cats
under generell anestesi. under general anesthesia.
(2) Deres virkning i å antagonisere okningen i hjertevirksomheten indusert ved injisering av isoproterenol i ikke-anestetiserte hunder. (3) Deres anti-arrytmiske virkning på ikke-anestetiserte kaniner behandlet med bariumklorid. (4) Deres hypotensive virkning på ikke-anestetiserte hunder med neurogen hypertensjon. (2) Their action in antagonizing the increase in cardiac activity induced by injection of isoproterenol in unanesthetized dogs. (3) Their anti-arrhythmic action on non-anesthetized rabbits treated with barium chloride. (4) Their hypotensive effect on non-anesthetized dogs with neurogenic hypertension.
Forbindelsene ble funnet å antagonisere responsen på isoproterenol. Særlig er den (3-adrenergisk blokkerende aktivitet av l-isopropylamino-3-(1<1>,4'-etan-1',2',31,4'-tetrahydronaft-5'-yloksy)propan-2-ol blitt undersokt: The compounds were found to antagonize the response to isoproterenol. In particular, the (3-adrenergic blocking activity of l-isopropylamino-3-(1<1>,4'-ethan-1',2',31,4'-tetrahydronaphth-5'-yloxy)propan-2-ol been investigated:
Virkningen av forbindelsen på ikke-anestetiserte hunder i å antagonisere okningen av hjertevirksomheten (tachycardia) indusert ved injisering av isoproterenol ble bestemt og sammen-lignet med propanolol, til hvilken verdien 1 ble gitt for dets (3-adrenergiske reseptorblokkerende aktivitet. Aktiviteten for sotaloi og propranolol er også angitt. The effect of the compound on unanesthetized dogs in antagonizing the increase in cardiac activity (tachycardia) induced by injection of isoproterenol was determined and compared with propranolol, to which the value of 1 was given for its (3-adrenergic receptor blocking activity. The activity for sotaloi and propranolol is also indicated.
Forbindelse (1) reduserte den primære hjertevirksomhet hos ikke-anestetiserte og anestetiserte dyr. Compound (1) reduced the primary cardiac activity in non-anesthetized and anesthetized animals.
Dessuten viser forbindelse (1) stbrre anti-arrytmisk og hypo-tensiv virkning enn proranolol. Resultatene som oppnås på anestetiserte katter bekrefter resultatene på hunder. Moreover, compound (1) shows a stronger anti-arrhythmic and hypotensive effect than proranolol. The results obtained in anesthetized cats confirm the results in dogs.
Oppfinnelsen illustreres av de folgende eksempler. The invention is illustrated by the following examples.
EKSEMPEL 1 EXAMPLE 1
6-(glycid-3'-yloksy)-1,4-etano-l1,21, 3',4'-tetrahydronaftalen (8,1 g) i isopropylamin (50 ml) ble tilbakelopsbehandlet i 24 timer. Etter fordampning av det overskytende isopropylamin i vakuum ble resten omdannet til isopropylamino-3-(1',4'-etano-1', 2',3', 4'-tetrahydronaft-6'-yloksy)-propan-2-ol, smp. 118-121°C. 6-(glycid-3'-yloxy)-1,4-ethano-1,21,3',4'-tetrahydronaphthalene (8.1 g) in isopropylamine (50 ml) was refluxed for 24 hours. After evaporation of the excess isopropylamine in vacuo, the residue was converted to isopropylamino-3-(1',4'-ethano-1',2',3',4'-tetrahydronaphth-6'-yloxy)-propan-2-ol , m.p. 118-121°C.
EKSEMPEL 2 EXAMPLE 2
17 g 5-hydroksy-l,4-etano-l,2,3,4-tetrahydronaftalin, 70 ml epiklorhydrin og 4 dråper piperidin ble oppvarmet i 17 timer til 100°C. Etter fordampning av opplbsningsmiddelet ble resten ekstrahert med dietyleter og vasket med vann, og etter fordampning av opplbsningsmiddelet ble 23,2 g 3-(1<1>,4'-etano-11, 2', 31,41-tetrahydronaft-51-yloksy)-l-klor-propan-2-ol oppnådd, kp. 175 til 180°C/0,1 mm. 20 g av denne forbindelse ble oppvarmet i 15 ml isopropylamin og 15 ml toluen over natten til 120°C. Etter fordampning av opplbsningsmiddelet og det overskytende amin ble resten omsatt i etylacetat med citronsyre til 25,1 g l-isopropylamino-3-(l<1>,4'-etano-11,21,31,4'-tetrahydronaft-5<1->yloksy)propan-2-ol-citrat, smeltepunkt 75°C 17 g of 5-hydroxy-1,4-ethane-1,2,3,4-tetrahydronaphthalene, 70 ml of epichlorohydrin and 4 drops of piperidine were heated for 17 hours at 100°C. After evaporation of the solvent, the residue was extracted with diethyl ether and washed with water, and after evaporation of the solvent, 23.2 g of 3-(1<1>,4'-ethane-11,2',31,41-tetrahydronaphth-51- yloxy)-1-chloro-propan-2-ol obtained, bp. 175 to 180°C/0.1 mm. 20 g of this compound was heated in 15 ml of isopropylamine and 15 ml of toluene overnight at 120°C. After evaporation of the solvent and the excess amine, the residue was reacted in ethyl acetate with citric acid to give 25.1 g of 1-isopropylamino-3-(1<1>,4'-ethane-11,21,31,4'-tetrahydronaphth-5< 1->yloxy)propan-2-ol citrate, melting point 75°C
til 78°C. to 78°C.
På tilsvarende måte etterat resten var blitt tatt opp i dietyleter og behandlet med gassformet hydrogenklorid, ble fblgende hydroklorider oppnådd. l-tert.-butylamino-3-(1',4'-etano-1',21,3',4'-tetrahydronaft-5<1->yloksy)-propan-2-ol, smeltepunkt 169 til 171°C; l-sek.-butylamino-3-(11, 4'-etano-1',21,31,4'-tetrahydronaft-51-yloksy)-propan-2-ol, smeltepunkt 150 til 159°C. In a similar manner, after the residue had been taken up in diethyl ether and treated with gaseous hydrogen chloride, the following hydrochlorides were obtained. 1-tert-butylamino-3-(1',4'-ethano-1',21,3',4'-tetrahydronaphth-5<1->yloxy)-propan-2-ol, mp 169 to 171° C; 1-sec-butylamino-3-(11,4'-ethano-1',21,31,4'-tetrahydronaphth-51-yloxy)-propan-2-ol, mp 150 to 159°C.
EKSEMPEL 3 EXAMPLE 3
40 g 5-hydroksy-l,4-etano-l,2,3,4-tetrahydronaftalin, 40 g of 5-hydroxy-1,4-ethane-1,2,3,4-tetrahydronaphthalene,
160 ml epiklorhydrin og 6 dråper piperidin ble oppvarmet 160 ml of epichlorohydrin and 6 drops of piperidine were heated
17 timer til 100°C. Opplbsningsmiddelet ble fordampet og resten ble omrbrt 23 timer med 31 g natriumhydroksyd i 300 ml vann og ekstrahert med dietyleter. Etter fordampning av opplbsningsmiddelet ble resten destillert i vakuum, hvorved 44,9 g 5-(glycid-3'-yloksy)-1,4-etano-l,2,3,4-tetrahydronafta- 17 hours at 100°C. The solvent was evaporated and the residue was stirred for 23 hours with 31 g of sodium hydroxide in 300 ml of water and extracted with diethyl ether. After evaporation of the solvent, the residue was distilled in vacuo, whereby 44.9 g of 5-(glycid-3'-yloxy)-1,4-ethanol-1,2,3,4-tetrahydronaphtha-
lin ble oppnådd. 39 g av denne forbindelse ble oppvarmet i 150 ml isopropylamin i lbpet av 24 timer ved tilbakelbp. Det overskytende isopropylamin ble fordampet i vakuum og resten ble omdannet i dietyleter ved gassformet klorhydrogen til 40,5 g lin was obtained. 39 g of this compound were heated in 150 ml of isopropylamine over the course of 24 hours at reflux. The excess isopropylamine was evaporated in vacuo and the residue was converted in diethyl ether by gaseous hydrogen chloride to 40.5 g
hydroklorid av l-isopropylamino-3-(11,4'-etano-1', 2', 31, 4'-tetrahydronaft-5'-yloksy)-propan-2-ol, smeltepunkt 130 til 132°C. Folgende hydroklorider ble fremstilt på tilsvarende hydrochloride of 1-isopropylamino-3-(11,4'-ethano-1',2',31,4'-tetrahydronaphth-5'-yloxy)-propan-2-ol, mp 130 to 132°C. The following hydrochlorides were prepared similarly
måte: manner:
l-ter.-butylamino-3-(l1,4'-etano-1', 2',3',4'-tetrahydronaft-5'-yloksy)-propan-2-ol, smeltepunkt 169 til 171°Cj l-sek.-butylamino-3-(1',4'-etano-1',2•,3',4'-tetrahydronaft-5'-yloksy)-propan-2-ol, smeltepunkt 150 til 159°C. 1-tert-butylamino-3-(11,4'-ethano-1',2',3',4'-tetrahydronaphth-5'-yloxy)-propan-2-ol, melting point 169 to 171°Cj l -sec-butylamino-3-(1',4'-ethano-1',2•,3',4'-tetrahydronaphth-5'-yloxy)-propan-2-ol, mp 150 to 159°C.
EKSEMPEL 4 EXAMPLE 4
40 g av natriumsaltet av 5-hydroksy-l,4-etano-l, 2, 3,4-tetrahydronaftalin i 300 ml tetrahydrofuran ble tilsatt til en kokende opplosning av 1,3-diklorpropanon (25,5 g) i tetrahydrofuran (150 ml) i lbpet av 1,5 timer. Derpå ble opplbsningsmiddelet fordampet og resten vasket i eter med vann. Ved konsentrering og omkrystallisasjon fra heksan ble 35 g 1-(1',4'-etano-1', 2', 3',4'-tetrahydronaft-5'-yloksy)-3-klor-propan-2-on oppnådd. 13 g av dette produkt i 150 ml tetra-hydrof uran ble omsatt med 8,5 ml isopropylamin. Etter 24 timer ble saltet filtrert av og opplbsningsmiddelet fordampet. 40 g of the sodium salt of 5-hydroxy-1,4-ethanol-1,2,3,4-tetrahydronaphthalene in 300 ml of tetrahydrofuran was added to a boiling solution of 1,3-dichloropropanone (25.5 g) in tetrahydrofuran (150 ml) in the course of 1.5 hours. The solvent was then evaporated and the residue washed in ether with water. By concentration and recrystallization from hexane, 35 g of 1-(1',4'-ethano-1', 2', 3',4'-tetrahydronaphth-5'-yloxy)-3-chloro-propan-2-one was obtained . 13 g of this product in 150 ml of tetrahydrofuran were reacted with 8.5 ml of isopropylamine. After 24 hours the salt was filtered off and the solvent evaporated.
Resten ble opplost i 10%'ig klorhydrogensyre, ekstrahert med eter og klaret med aktivt kull. Opplbsningen ble behandlet med et overskudd av NaHC03 og ekstrahert med eter, og deretter ble eterekstraktet tbrket. Til den tbrkede opplosning i eter ble 5 g LiAlH^ tilsatt og blandingen oppvarmet i 6 timer ved tilbakelbp. Overskuddet av LiAlH^ ble spaltet med vann og 20% natriumhydroksyd, og det organiske materiale isolert med eter. Ved omkrystallisasjon fra cykloheksan ble 8,5 g l-iso-propylamino-3- (l1,4',-etano-1', 2',3',4'-tetrahydronaft-5'-yloksy)-propan-2-ol, smeltepunkt 102 til 103°C oppnådd. The residue was dissolved in 10% hydrochloric acid, extracted with ether and clarified with activated charcoal. The solution was treated with an excess of NaHCO 3 and extracted with ether, and then the ether extract was dried. To the concentrated solution in ether, 5 g of LiAlH 2 were added and the mixture heated for 6 hours at reflux. The excess of LiAlH^ was cleaved with water and 20% sodium hydroxide, and the organic material isolated with ether. By recrystallization from cyclohexane, 8.5 g of 1-iso-propylamino-3-(11,4',-ethano-1',2',3',4'-tetrahydronaphth-5'-yloxy)-propan-2- ol, melting point 102 to 103°C obtained.
EKSEMPEL 5 EXAMPLE 5
5,3 g 5-hydroksy-l,4-etano-l,2,3,4-tetrahydronaftalin i 50 ml 5.3 g of 5-hydroxy-1,4-ethane-1,2,3,4-tetrahydronaphthalene in 50 ml
*dimetylformamid og 4,9 g natriummetoksyd oppvarmes i en time til 50°C og deretter behandles den ennå varme blanding med *dimethylformamide and 4.9 g of sodium methoxide are heated for one hour to 50°C and then the still warm mixture is treated with
l-tert.-butylamino-3-klor-propan-2-ol-hydroklorid og får henstå 5 timer ved 120 til 125°C. Etter fjerning av dimetyl-formamidet i vakuum ble resten underkastet en fordeling mellom 5%'ig klorhydrogensyre og eter. Den vandige fase ble gjort alkalisk med 10%'ig natriumhydroksyd og ekstrahert med eter. Det eteriske skikt ble torket (Na2 SO^) og behandlet med en strom av gassformet klorhydrogen. Det utfallende faste stoff (4,5 g) ble filtrert av og omkrystallisert fra isopropanol/ petroleter. Derved ble hydrokloridet av l-tert.-butylamino-3-(11, 4'-etano-1',21,3',4'-tetrahydronaft-51-yloksy)propan-2-ol 1-tert-butylamino-3-chloro-propan-2-ol hydrochloride and allowed to stand for 5 hours at 120 to 125°C. After removal of the dimethylformamide in vacuo, the residue was partitioned between 5% hydrochloric acid and ether. The aqueous phase was made alkaline with 10% sodium hydroxide and extracted with ether. The ethereal layer was dried (Na 2 SO 4 ) and treated with a stream of gaseous hydrogen chloride. The precipitated solid (4.5 g) was filtered off and recrystallized from isopropanol/petroleum ether. Thereby, the hydrochloride of 1-tert-butylamino-3-(11,4'-ethano-1',21,3',4'-tetrahydronaphth-51-yloxy)propan-2-ol
. (3,9 g), smeltepunkt 169 til 171°C oppnådd. . (3.9 g), mp 169 to 171°C obtained.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2027869 | 1969-07-30 | ||
| IT2019370 | 1970-02-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO129042B true NO129042B (en) | 1974-02-18 |
Family
ID=26327437
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO294470A NO129042B (en) | 1969-07-30 | 1970-07-29 |
Country Status (13)
| Country | Link |
|---|---|
| JP (1) | JPS5010591B1 (en) |
| AT (1) | AT303700B (en) |
| BE (1) | BE753917A (en) |
| CH (1) | CH539017A (en) |
| CS (1) | CS163218B2 (en) |
| DE (1) | DE2037319C3 (en) |
| ES (1) | ES382297A1 (en) |
| FR (1) | FR2059580B1 (en) |
| GB (1) | GB1263035A (en) |
| IE (1) | IE34394B1 (en) |
| NL (1) | NL7011244A (en) |
| NO (1) | NO129042B (en) |
| SE (1) | SE368820B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1436860A (en) * | 1972-12-18 | 1976-05-26 | Syntex Inc | 5,8-dihydro-5,8-methanonaphthalene cardiovascular agents |
-
1970
- 1970-07-17 IE IE93470A patent/IE34394B1/en unknown
- 1970-07-22 GB GB3555070A patent/GB1263035A/en not_active Expired
- 1970-07-24 BE BE753917D patent/BE753917A/en unknown
- 1970-07-27 AT AT685570A patent/AT303700B/en not_active IP Right Cessation
- 1970-07-28 DE DE19702037319 patent/DE2037319C3/en not_active Expired
- 1970-07-29 NO NO294470A patent/NO129042B/no unknown
- 1970-07-29 NL NL7011244A patent/NL7011244A/xx unknown
- 1970-07-29 ES ES382297A patent/ES382297A1/en not_active Expired
- 1970-07-29 SE SE1040070A patent/SE368820B/xx unknown
- 1970-07-30 CH CH1153170A patent/CH539017A/en not_active IP Right Cessation
- 1970-07-30 FR FR7028201A patent/FR2059580B1/fr not_active Expired
- 1970-07-30 CS CS534870A patent/CS163218B2/cs unknown
- 1970-07-30 JP JP6646970A patent/JPS5010591B1/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| FR2059580A1 (en) | 1971-06-04 |
| CH539017A (en) | 1973-07-15 |
| NL7011244A (en) | 1971-02-02 |
| GB1263035A (en) | 1972-02-09 |
| DE2037319C3 (en) | 1973-11-22 |
| FR2059580B1 (en) | 1973-12-21 |
| IE34394B1 (en) | 1975-04-30 |
| ES382297A1 (en) | 1973-04-16 |
| CS163218B2 (en) | 1975-08-29 |
| AT303700B (en) | 1972-12-11 |
| BE753917A (en) | 1971-01-25 |
| DE2037319A1 (en) | 1971-02-11 |
| IE34394L (en) | 1971-01-30 |
| JPS5010591B1 (en) | 1975-04-22 |
| DE2037319B2 (en) | 1973-04-26 |
| SE368820B (en) | 1974-07-22 |
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