DE3546751C2 - New 1-(methoxy)methyl 3-oxo-4-cyano-hexa:hydro isoquinoline derivs. - Google Patents
New 1-(methoxy)methyl 3-oxo-4-cyano-hexa:hydro isoquinoline derivs.Info
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- DE3546751C2 DE3546751C2 DE3546751A DE3546751A DE3546751C2 DE 3546751 C2 DE3546751 C2 DE 3546751C2 DE 3546751 A DE3546751 A DE 3546751A DE 3546751 A DE3546751 A DE 3546751A DE 3546751 C2 DE3546751 C2 DE 3546751C2
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- pyridyl
- oxo
- methyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/385—Saturated compounds containing a keto group being part of a ring
- C07C49/403—Saturated compounds containing a keto group being part of a ring of a six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/385—Saturated compounds containing a keto group being part of a ring
- C07C49/517—Saturated compounds containing a keto group being part of a ring containing ether groups, groups, groups, or groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/657—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
Description
Die Erfindung betrifft das pyridinsubstituierte Cyclohexanon-De rivat gemäß Anspruch 1, das ein besonders wertvolles Zwischen produkt auf dem gegebenenfalls mehrstufigen Weg zur Synthese von medizinisch vorteilhaften Isochinolinderivaten ist, wie z. B. in DE-PS 35 26 693 und DE-PS 35 46 572 näher erläutert. Ferner betrifft die Erfindung Herstellung und Verwendung des Produkts nach Anspruch 1.The invention relates to the pyridine-substituted cyclohexanone-De rivat according to claim 1, which is a particularly valuable intermediate product on the possibly multi-stage route to synthesis of medically advantageous isoquinoline derivatives is how e.g. B. in DE-PS 35 26 693 and DE-PS 35 46 572 explained in more detail. Furthermore concerns The invention Production and use of the product according to claim 1.
In NL-OS 65 13 784 ist die Verbindung 4-(2-Pyridyl)cyclohexa non genannt, jedoch bei ihrer Darstellungsarbeitsweise ohne qualitative und quantitative Kontrollangaben zu Ausbeute und Reinheit; auch ist der präparative Aufwand recht umfangreich.In NL-OS 65 13 784 the compound is 4- (2-pyridyl) cyclohexa called non, but in their way of presenting without qualitative and quantitative control information on yield and Purity; the preparative effort is also quite extensive.
Digitalis-Zubereitungen sind üblicherweise bei der Behandlung der Herzinsuffizienz als Herzmittel benutzt worden (vergleiche z. B. Iyakuhin Yoran, Seiten 324-327, 1977, Yakugyo Jihosha). Digitalis preparations are usually in treatment heart failure has been used as a heart remedy (cf. e.g. B. Iyakuhin Yoran, pages 324-327, 1977, Yakugyo Jihosha).
Sie erfordern hohe Aufmerksamkeit bei der medizinischen Anwendung, da sie eine geringe Sicherheitszone haben, so daß Nebenwirkungen schnell auftreten können, z. B. Arrhythmia etc. Es sind auch andere Herzmittel beschrieben worden, wie Nicotinnitril-Derivate (siehe z. B. JP-OS 70868/1982), Imidazolon-Derivate (siehe z. B. JP-OS 155368/1984) und Dihydropyridazinon-Derivate (siehe z. B. JP-OS 74679/1983), wobei jedoch geringe cardiotonische Aktivität, enge Sicherheitszonen, Zunahme bei der rhythmi schen Bewegung des Herzmuskels, hohe Toxizität gegenüber Tieren etc. beobachtet werden.They require high levels of medical attention Application because they have a small security zone, so that side effects can occur quickly, e.g. B. Arrhythmia, etc. Other heart remedies have also been described such as nicotinitrile derivatives (see e.g. JP-OS 70868/1982), imidazolone derivatives (see e.g. JP-OS 155368/1984) and dihydropyridazinone derivatives (see e.g. JP-OS 74679/1983), but low cardiotonic Activity, tight security zones, increase in rhythmi movement of the heart muscle, high toxicity towards Animals etc. are observed.
Die Aufgabe der Erfindung liegt also in der Schaffung einer solchen chemischen Verbindung, die auf dem ggf. mehrstufigen Weg für die Synthese der angesprochenen Isochinolinderivate besonders vorteilhaft eingesetzt werden kann.The object of the invention is therefore to create a such chemical compound, which may be multi-stage Path for the synthesis of the addressed isoquinoline derivatives can be used particularly advantageously.
Erfindungsgemäß wird diese Aufgabe durch die Bereitstellung des Cyclohexanonderivats gemäß Hauptanspruch gelöst. Das Aus führungsbeispiel zeigt dazu die wenig aufwendige präparative Methode und die klare Definierung dieser Substanz mit Ausbeute und physikalischen Prüfdaten.According to the invention, this object is achieved by the provision of the cyclohexanone derivative solved according to the main claim. The end The example shows the less complex preparative Method and the clear definition of this substance with yield and physical test data.
Aus den Unteransprüchen sind weitere vorteilhafte Ausführungsformen der Erfindung ersichtlich.Further advantageous embodiments of the Invention evident.
Die mit Hilfe des erfindungsgemäßen Cyclohexanonderivats her gestellten Pharmaka bieten breite Sicherheitszonen; sie sind frei von Nebeneffekten; sie zeigen hohe cardiotonische Aktivi tät und geringe Toxizität. Unter den Wegen zur Darstellung der angesprochenen Isochinolinderivate sind solche mit Hilfe des erfindungsgemäßen Cyclohexanonderivats besonders vorteilhaft.Those with the help of the cyclohexanone derivative according to the invention provided pharmaceuticals offer wide safety zones; they are free of side effects; they show high cardiotonic activity and low toxicity. Among the ways to represent the Isoquinoline derivatives addressed are those with the aid of Cyclohexanone derivative according to the invention particularly advantageous.
Zu der erfindungsgemäßen Substanz gemäß Formelbild VI kommt man dadurch, daß manThe substance according to formula VI according to the invention is obtained by
- a) 1,4-Cyclohexandion-Monoethylenketal der Formel III mit 4-Brompyridin unter Bildung der Verbindung IV kondensierta) 1,4-cyclohexanedione monoethylene ketal of the formula III with 4-bromopyridine to form compound IV condensed
- b) die Verbindung IV einer Dehydratation unter Bildung der Verbin dung V unterwirft, undb) the compound IV dehydration to form the compound V subjects, and
- c) die Verbindung V einer Hydrierung in einer Mineralsäure unterwirft.c) subjecting compound V to hydrogenation in a mineral acid.
Im obigen Schema wird die Verbindung III, nämlich 1,4-Cyclohe xandion-Monoethylenketal, mit 4-Brompyridin in Gegenwart von n-Butyllithium kondensiert und ergibt eine Verbindung der Formel IV. Diese Verbindung IV wird z. B. mit Thionylchlorid in Pyridin zur Verbindung V umgesetzt, die man in einer Mine ralsäure zur Verbindung VI hydriert.In the above scheme, compound III, namely 1,4-cyclohe xandione monoethylene ketal, with 4-bromopyridine in the presence of n-Butyllithium condenses and gives a compound of Formula IV. This compound IV is e.g. B. with thionyl chloride implemented in pyridine to compound V, which is in a mine hydrogenated to compound VI hydrogenated.
Die Verbindung VI kann zur Verbindung VII acyliert werden, wie in der DE-PS 35 46 572 beschrieben ist. Substanzen gemäß For mel VII gehen direkt in die Synthese der Isochinolinderivate ein, wie in DE-PS 35 26 693 und DE-PS 35 46 572 näher darge stellt ist.Compound VI can be acylated to compound VII, such as is described in DE-PS 35 46 572. Substances according to For mel VII go directly into the synthesis of the isoquinoline derivatives a, as in DE-PS 35 26 693 and DE-PS 35 46 572 Darge closer represents is.
Die erfindungsgemäße Verbindung VI ist besonders gut brauch bar als Zwischenprodukt für die vorstehend genannte Her stellung der Isochinolinderivate.Compound VI according to the invention is particularly useful bar as an intermediate for the above mentioned position of the isoquinoline derivatives.
Nachstehend wird die Erfindung anhand eines Ausführungsbei spiels näher erläutert. The invention will now be described by way of an embodiment explained in more detail.
(1) 4-Hydroxy-4-(4-pyridyl)cyclohexanon-ethylen-acetal:
35 ml Ether wurden auf -78°C gekühlt und dann 20 ml einer
1,6-molaren Lösung von n-Butyllithium in Hexan hinzugegeben.
Zu der erhaltenen Mischung gab man 5 g 4-Brompyridin, gelöst
in 30 ml Ether. Danach fügte man 5 g 1,4-Cyclohexandion
monoethylen-acetal, gelöst in 30 ml Tetrahydrofuran, hinzu.
Nach Beendigung der Umsetzung goß man die Reaktionsmischung
in eine gesättigte wässerige Lösung von Ammoniumchlorid.
Das Gemisch wurde mit Chloroform extrahiert, und der
Extrakt wurde gereinigt, wobei sich
5 g 4-Hydroxy-4-(4-pyridyl)cyclohexanon-ethylen-acetal ergeben.(1) 4-Hydroxy-4- (4-pyridyl) cyclohexanone ethylene acetal:
35 ml of ether were cooled to -78 ° C and then 20 ml of a 1.6 molar solution of n-butyllithium in hexane was added. 5 g of 4-bromopyridine, dissolved in 30 ml of ether, were added to the mixture obtained. Then 5 g of 1,4-cyclohexanedione monoethylene acetal, dissolved in 30 ml of tetrahydrofuran, were added. After the reaction had ended, the reaction mixture was poured into a saturated aqueous solution of ammonium chloride. The mixture was extracted with chloroform and the extract was purified to give 5 g of 4-hydroxy-4- (4-pyridyl) cyclohexanone-ethylene-acetal.
F: 165,5-167,5°C. NMRδ : 1.6-2.2 (8H, m), 3.9 (1H, s), 4.00 (4H, s), 7.45 (2H, dd) und 8.44 (2H, dd).F: 165.5-167.5 ° C. NMR δ: 1.6-2.2 (8H, m), 3.9 (1H, s), 4.00 (4H, s), 7.45 (2H, dd) and 8.44 (2H, dd).
(2) 4-(4-Pyridyl)cyclohex-3-enon-ethylen-acetal:
5 g 4-Hydroxy-4-(4-pyridyl)cyclohexanon-ethylen-acetal wur
den in 40 ml Pyridin gelöst, und dann gab man bei -10°C.
8 ml Thionylchlorid hinzu. Die erhaltene Mischung wurde bei
0°C gerührt und auf Eis gegossen. Dann gab man eine überschüs
sige Menge einer wässerigen Lösung von Natriumhydroxid hinzu.
Das Gemisch wurde mit Methylenchlorid extrahiert und der Extrakt
wurde gereinigt, wobei man 4 g 4-(4-Pyridyl)cyclohex-3-enon-
ethylen-acetal erhielt. F: 67-70°C. NMRδ : 1.86
(2H, t), 2.4-2.7 (4H, m), 4.04 (4H, s), 6.24 (1H, t),
7.28 (2H, d) und 8.52 (2H, d).(2) 4- (4-pyridyl) cyclohex-3-enone-ethylene-acetal:
5 g of 4-hydroxy-4- (4-pyridyl) cyclohexanone-ethylene-acetal were dissolved in 40 ml of pyridine, and then it was added at -10 ° C. Add 8 ml of thionyl chloride. The resulting mixture was stirred at 0 ° C and poured onto ice. Then an excess amount of an aqueous solution of sodium hydroxide was added. The mixture was extracted with methylene chloride and the extract was purified to give 4 g of 4- (4-pyridyl) cyclohex-3-enone-ethylene-acetal. F: 67-70 ° C. NMR δ: 1.86 (2H, t), 2.4-2.7 (4H, m), 4.04 (4H, s), 6.24 (1H, t), 7.28 (2H, d) and 8.52 (2H, d).
(3) 4-(4-Pyridyl)cyclohexanon:
4 g 4-(4-Pyridyl)cyclohex-3-enon-ethylen-acetal wurden in
70 ml einer 0,5-normalen Chlorwasserstoffsäure gelöst, und
dann gab man 400 mg eines 10%igen Palladium/Kohle hinzu, um
die Ausgangsverbindung bei Normaltemperatur und Normal
druck zu hydrieren. Nach Beendigung der Umsetzung wurde
der Katalysator entfernt, und man machte die Reaktionsmi
schung mit einer wässerigen Lösung von Natriumhydroxid al
kalisch und extrahierte sie mit Methylenchlorid. Man erhielt
2,7 g 4-(4-Pyridyl)cyclohexanon. NMRδ : 1.7-2.3
(4H, m), 2.4-2.6 (4H, m), 2.8-3.2 (1H, m), 7.15 (2H, d)
und 8.51 (2H, m).(3) 4- (4-pyridyl) cyclohexanone:
4 g of 4- (4-pyridyl) cyclohex-3-enone-ethylene-acetal was dissolved in 70 ml of 0.5 normal hydrochloric acid, and then 400 mg of a 10% palladium / carbon was added to give the starting compound Hydrogenate normal temperature and normal pressure. After the completion of the reaction, the catalyst was removed and the reaction mixture was made alkaline with an aqueous solution of sodium hydroxide and extracted with methylene chloride. 2.7 g of 4- (4-pyridyl) cyclohexanone were obtained. NMR δ: 1.7-2.3 (4H, m), 2.4-2.6 (4H, m), 2.8-3.2 (1H, m), 7.15 (2H, d) and 8.51 (2H, m).
Die Ausbeute beträgt 48%.The yield is 48%.
2-Acetyl-4-(4-pyridyl)cyclohexanon:
3,2 ml Diisopropylamin wurden in 40 ml Tetrahydrofuran gelöst,
und dann gab man bei -20°C 14,2 ml einer 1,6 molaren Lösung
von n-Butyllithium in Hexan hinzu. Eine Lösung
von 2 g 4-(4-Pyridyl)cyclohexanon (gem. Beispiel) in 40 ml
Tetrahydrofuran gab man bei -40°C zum Gemisch hinzu.
Die erhaltene Reaktionsmischung wurde auf -78°C
abgekühlt, und dann fügte man 2,5 g Acetylimidazol, gelöst
in 40 ml Tetrahydrofuran, hinzu. Nach dem Rühren bei Zimmertem
peratur wurde die Reaktionsmischung auf Eis gegossen
und mit Ether gewaschen. Die wässerige Phase wurde mit Ammo
niumchlorid gesättigt und mit Methylenchlorid extrahiert.
Man erhielt 1,65 g 2-Acetyl-4-(4-pyridyl)cyclohexanon.
NMRδ : 1.7-2.2 (3H, m), 2.16 (3H, s), 2.3-2.6 (3H, m),
2.6-2.9 (1H, m), 7.10 (2H, dd), 8.55 (2H, dd) und 15.7
(1H, s).2-acetyl-4- (4-pyridyl) cyclohexanone:
3.2 ml of diisopropylamine were dissolved in 40 ml of tetrahydrofuran, and then 14.2 ml of a 1.6 molar solution of n-butyllithium in hexane were added at -20 ° C. A solution of 2 g of 4- (4-pyridyl) cyclohexanone (according to Example) in 40 ml of tetrahydrofuran was added to the mixture at -40 ° C. The reaction mixture obtained was cooled to -78 ° C., and 2.5 g of acetylimidazole, dissolved in 40 ml of tetrahydrofuran, were then added. After stirring at room temperature, the reaction mixture was poured onto ice and washed with ether. The aqueous phase was saturated with ammonium chloride and extracted with methylene chloride. 1.65 g of 2-acetyl-4- (4-pyridyl) cyclohexanone were obtained. NMRδ: 1.7-2.2 (3H, m), 2.16 (3H, s), 2.3-2.6 (3H, m), 2.6-2.9 (1H, m), 7.10 (2H, dd), 8.55 (2H, dd) and 15.7 (1H, s).
4-Cyan-2,3,5,6,7,8-hexahydro-1-methyl-3-oxo-7-
(4-pyridyl)isochinolin:
1,65 g 2-Acetyl-4-(4-pyridyl)cyclohexanon (gemäß Beispiel) und
0,64 g Cyanacetamid wurden in Ethanol gelöst und eine geringe Menge
Piperidin wurde hinzugegeben. Die erhaltene Reaktionsmischung
wurde 7 Stunden am Rückfluß erhitzt. Nach Beendigung der
Umsetzung wurden die ausgefallenen Kristalle abfiltriert,
und man erhielt 0,7 g 4-Cyan-2,3,5,6,7,8-hexahydro-1-methyl-
3-oxo-7-(4-pyridyl)isochinolin. F: 310°C (Zers.).
NMRδ : 1.7-2.1 (2H, m), 2.22 (3H, s), 2.3-2.7
(2H, m), 2.8-3.0 (3H, m), 7.35 (2H, dd) und 8.50 (2H, dd).4-cyan-2,3,5,6,7,8-hexahydro-1-methyl-3-oxo-7- (4-pyridyl) isoquinoline:
1.65 g of 2-acetyl-4- (4-pyridyl) cyclohexanone (according to the example) and 0.64 g of cyanoacetamide were dissolved in ethanol and a small amount of piperidine was added. The reaction mixture obtained was heated under reflux for 7 hours. After the completion of the reaction, the precipitated crystals were filtered off, and 0.7 g of 4-cyano-2,3,5,6,7,8-hexahydro-1-methyl-3-oxo-7- (4-pyridyl) was obtained. isoquinoline. F: 310 ° C (dec.). NMR δ: 1.7-2.1 (2H, m), 2.22 (3H, s), 2.3-2.7 (2H, m), 2.8-3.0 (3H, m), 7.35 (2H, dd) and 8.50 (2H, dd).
Die mit Hilfe des beschriebenen Cyclohexanonderivats auf vor teilhafte Weise hergestellten Isochinolinderivate sind äußerst brauchbare cardiotonische Pharmaka und von äußerst geringer Toxizität, d. h. also mit breiter Sicherheitszone. Die cardio tonische Wirksamkeit läßt sich an pharmakologischen Standard-Test methoden zeigen; dabei resultieren Werte von bedeutender Verbesserung der Herzfunktion unter Anästhesie, wenn z. B. durch intravenöse Propranolol-Verabreichung eine Reduzierung entstanden ist.The on with the help of the described cyclohexanone derivative Isoquinoline derivatives produced in some ways are extreme useful cardiotonic drugs and of extremely low Toxicity, d. H. with a wide security zone. The cardio Tonic effectiveness can be demonstrated on standard pharmacological test show methods; this results in values of significant Improvement of cardiac function under anesthesia when e.g. B. a reduction by intravenous propranolol administration arose.
Claims (3)
sowie deren therapeutisch verträgliche Salze. 2. Use of the compound of formula VI according to claim 1, namely as a starting material for the preparation of the isoquinoline derivatives according to formula I, namely wherein R₁ is a methyl or a methoxymethyl group and R₂ and R₃ are each a hydrogen atom or a lower alkyl, a lower alkoxyl group, cyclohexyl, phenyl, a substituted phenyl group, pyridyl or an oxo (= O) group,
and their therapeutically tolerable salts.
- a) 1,4-Cyclohexandion-Monoethylenketal der Formel III mit 4-Brompyridin in Gegenwart von n-Butyllithium unter Bildung der Verbindung IV kondensiert,
- b) die Verbindung IV mit Thionylchlorid in Pyridin einer Dehydratation unter Bildung der Verbindung V unterwirft, und
- c) die Verbindung V einer Hydrierung in einer Mineralsäure unterwirft.
- a) 1,4-cyclohexanedione monoethylene ketal of the formula III with 4-bromopyridine in the presence of n-butyllithium to form compound IV condensed,
- b) compound IV with thionyl chloride in pyridine dehydration to form compound V subjects, and
- c) subjecting compound V to hydrogenation in a mineral acid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15410884A JPS6136266A (en) | 1984-07-26 | 1984-07-26 | Isoquinoline derivative and remedial composition containing same as active constituent |
| DE3546572A DE3546572C2 (en) | 1984-07-26 | 1985-07-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3546751C2 true DE3546751C2 (en) | 1997-02-13 |
Family
ID=25839461
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE3546751A Expired - Fee Related DE3546751C2 (en) | 1984-07-26 | 1985-07-25 | New 1-(methoxy)methyl 3-oxo-4-cyano-hexa:hydro isoquinoline derivs. |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE3546751C2 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL6513784A (en) * | 1964-10-26 | 1966-04-27 |
-
1985
- 1985-07-25 DE DE3546751A patent/DE3546751C2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL6513784A (en) * | 1964-10-26 | 1966-04-27 |
Non-Patent Citations (2)
| Title |
|---|
| J. Amer. Chem. Soc. 78, 6163, 1956 * |
| Tetrahedron Letters 7, 599-602, 1971 * |
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