CH386441A - Process for the preparation of derivatives of the lysergic acid series substituted on the indole nitrogen - Google Patents
Process for the preparation of derivatives of the lysergic acid series substituted on the indole nitrogenInfo
- Publication number
- CH386441A CH386441A CH197061A CH197061A CH386441A CH 386441 A CH386441 A CH 386441A CH 197061 A CH197061 A CH 197061A CH 197061 A CH197061 A CH 197061A CH 386441 A CH386441 A CH 386441A
- Authority
- CH
- Switzerland
- Prior art keywords
- lysergic acid
- derivatives
- acid series
- general formula
- indole nitrogen
- Prior art date
Links
- ZAGRKAFMISFKIO-QMTHXVAHSA-N lysergic acid Chemical group C1=CC(C2=C[C@H](CN([C@@H]2C2)C)C(O)=O)=C3C2=CNC3=C1 ZAGRKAFMISFKIO-QMTHXVAHSA-N 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 5
- DCBDOYDVQJVXOH-UHFFFAOYSA-N azane;1h-indole Chemical compound N.C1=CC=C2NC=CC2=C1 DCBDOYDVQJVXOH-UHFFFAOYSA-N 0.000 title description 3
- 238000002360 preparation method Methods 0.000 title description 2
- 239000002253 acid Substances 0.000 claims description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- ZAGRKAFMISFKIO-UHFFFAOYSA-N Isolysergic acid Natural products C1=CC(C2=CC(CN(C2C2)C)C(O)=O)=C3C2=CNC3=C1 ZAGRKAFMISFKIO-UHFFFAOYSA-N 0.000 claims description 5
- -1 alkali metal amide Chemical class 0.000 claims description 4
- 150000002896 organic halogen compounds Chemical class 0.000 claims description 4
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001447 alkali salts Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 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
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 description 4
- AMQINEYJSLILRT-XMSQKQJNSA-N C(C1=CC=CC=C1)NC(=O)[C@H]1CN(C)[C@@H]2CC3=CN(C4=CC=CC(C2=C1)=C34)C Chemical compound C(C1=CC=CC=C1)NC(=O)[C@H]1CN(C)[C@@H]2CC3=CN(C4=CC=CC(C2=C1)=C34)C AMQINEYJSLILRT-XMSQKQJNSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- ORBSYPFBZQJNJE-MPKXVKKWSA-N (6ar,9r,10ar)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-carboxylic acid Chemical compound C1=CC([C@H]2C[C@H](CN([C@@H]2C2)C)C(O)=O)=C3C2=CNC3=C1 ORBSYPFBZQJNJE-MPKXVKKWSA-N 0.000 description 2
- 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 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- GIUWLXABHBAKDK-AUUYWEPGSA-N (6aR,9R)-N-cyclopentyl-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide Chemical compound O=C([C@H]1CN([C@H]2C(C=3C=CC=C4NC=C(C=34)C2)=C1)C)NC1CCCC1 GIUWLXABHBAKDK-AUUYWEPGSA-N 0.000 description 1
- UUYMPWWTAQZUQB-QMTHXVAHSA-N (6ar,9r)-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-carbohydrazide Chemical compound C1=CC(C2=C[C@H](CN([C@@H]2C2)C)C(=O)NN)=C3C2=CNC3=C1 UUYMPWWTAQZUQB-QMTHXVAHSA-N 0.000 description 1
- QNRATNLHPGXHMA-XZHTYLCXSA-N (r)-(6-ethoxyquinolin-4-yl)-[(2s,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]methanol;hydrochloride Chemical compound Cl.C([C@H]([C@H](C1)CC)C2)CN1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OCC)C=C21 QNRATNLHPGXHMA-XZHTYLCXSA-N 0.000 description 1
- REMVRCBDCIZKBR-FOIQADDNSA-N C1(CCCC1)NC(=O)[C@H]1CN(C)[C@@H]2CC3=CN(C4=CC=CC(C2=C1)=C34)C Chemical compound C1(CCCC1)NC(=O)[C@H]1CN(C)[C@@H]2CC3=CN(C4=CC=CC(C2=C1)=C34)C REMVRCBDCIZKBR-FOIQADDNSA-N 0.000 description 1
- 206010007270 Carcinoid syndrome Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- FIMJSWFMQJGVAM-UHFFFAOYSA-N chloroform;hydrate Chemical compound O.ClC(Cl)Cl FIMJSWFMQJGVAM-UHFFFAOYSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von am Indolstickstof substituierten Derivaten der Lysergsäure-Reihe Es wurde gefunden, dass man zu am Indolstick- stoff substituierten Derivaten der Lysergsäure- und der Dihydrolysergsäure-Reihe der allgemeinen For-
EMI0001.0007
mel <SEP> I, <SEP> C <SEP> 0-R1
<tb> N <SEP> -C <SEP> H3
<tb> I
<tb> N
<tb> R2 worin R1 den Cyclopentylamino-,
den Benzylamino- oder den 1-Piperidinorest und R2 eine Alkyl- oder Aralkylgruppe bedeuten und
EMI0001.0016
für die Gruppierung
EMI0001.0018
steht, gelangen kann,
indem man Derivate der Lysergsäure- oder der Dihydrolysergsäure-Reihe der allgemeinen Formel 1I
EMI0001.0022
in flüssigem Ammoniak mit einem Alkaliamid be handelt und das entstandene Alkalisalz im gleichen Lösungsmittel mit einer organischen Halogenverbin dung der allgemeinen Formel III, Hal-R. III worin Hal für Brom oder Jod steht, umsetzt.
Die praktische Ausführung des Verfahrens ge staltet sich beispielsweise so, dass man das Alkaliamid in der Reaktionslösung selbst herstellt, indem man ein Alkalünetall, vorzugweise Natrium oder Kalium, in flüssigem Ammoniak löst, und diese Lösung, z. B.
durch Versetzen mit Ferrinitrat, oxydiert. Alsdann gibt man ein Lysergsäure- oder Dihydrolysergsäure- Derivat der Formel II zu und versetzt das Gemisch kurze Zeit nach erfolgter Lösung mit der gewünsch ten organischen Halogenverbindung der Formel III. Bei den Derivaten der Lysergsäure selbst wird so wohl das Alkaliamid als auch die organische Halo genverbindung zur Vermeidung von Nebenreaktionen nur in geringem,
höchstens zweifachem überschuss angewendet, während bei den Derivaten der Dihy- drolysergsäure auch ein grösserer überschuss, z. B. bis zum zehnfachen, angewendet werden darf.
Zur Aufarbeitung wird der Ammoniak ver dampft, und der Rückstand in einem binären Lö- sungsmittelsystem, z. B. Chloroform-Wasser, ' unter Schütteln aufgenommen. Das nach dem Verdampfen des Chloroforms zurückbleibende Basengemisch wird gegebenenfalls an Aluminiumoxyd chromatographiert und das gewünschte Endprodukt durch Kristallisa tion gereinigt.
Die erfindungsgemäss hergestellten Derivate der Lysergsäure- und der Dihydrolysergsäure-Reihe sind bei Raumtemperatur zum Teil sehr schön kristalli sierte Verbindungen, die mit geeigneten Säuren wasserlösliche, kristallisierte, beständige Salze bilden. Sie geben mit dem Kellerschen Farbreagens positive Farbreaktionen.
Die nach dem vorliegenden Verfahren herge stellten Verbindungen zeichnen sich durch starke serotonin-hemmende Wirkung aus. Sie sind deshalb zur therapeutischen Verwendung bei arthritischen, allergischen und entzündlichen Erscheinungen ge eignet. Ausserdem ist die klinische Verwendung der Verbindungen in solchen Fällen angezeigt, bei denen die Serotonin-Bildung durch das enterochromaffine System (Carcinoid-Syndrom) abnorm erhöht ist.
Da Serotonin ein physiologischer Wirkstoff ist, der in den verschiedensten Organen und speziell auch im Gehirn vorkommt, eignen sich die Verbindungen auch zur Behandlung von psychischen Erkrankun gen.
Die als Ausgangssubstanzen zur Verwendung gelangenden Verbindungen der Formel II, worin R1 die Cyclopentylamino- oder die Benzylaminogruppe oder den 1-Piperidinorest bedeutet, werden z. B. hergestellt, indem man ein Lysergsäure- oder Di- hydrolysergsäure-hydrazid der allgemeinen Formel IV,
EMI0002.0020
worin die gleiche Bedeutung wie in Formel 1I besitzt,
EMI0002.0022
mit salpetriger Säure in das Azid überführt und dieses mit dem gewünschten Amin umsetzt.
In den nachfolgenden Beispielen erfolgen alle Temperaturangaben in Celsiusgraden. Die Schmelz punkte sind nicht korrigiert.
<I>Beispiel 1</I> 1-Methyl-d lysergsäure-cyclopentylamid Man löst 0,136 g Natrium in 40 cm3 flüssigem Ammoniak, oxydiert mit Ferrinitrat zum Natrium- amid und gibt hierauf zur entfärbten Lösung unter Rühren 0,8 g d-Lysergsäurecyclopentylamid [Smp. 121-122 (Zers.)] zu. Die Lösung wird nach 10 Minuten mit 0,75 cm33 Methyljodid versetzt.
Nach weiteren 10 Minuten wird der Ammoniak verdampft, der Rückstand zwischen Wasser und Chloroform ausgeschüttelt und das nach Verdampfen des Chloroforms erhaltene Rohprodukt aus Essigsäure- äthylester kristallisiert.
Rhombische Platten vom Smp. 163-165 . Kellersche Farbreaktion: blau.
EMI0002.0042
(c = 0,5 in Pyridin). <I>Beispiel 2</I> 1-Methyl-d-lysergsäurebenzylamid In analoger Weise wie in Beispiel 1 beschrieben, wird durch Umsetzung von d-Lysergsäurebenzyl- amid mit Methyljodid das 1-Methyl-d-lysergsäure- benzylamid hergestellt und anschliessend ins Bi- maleinat übergeführt 1 -Methyl-d-lysergsäurebenzylamid:
Nadeln aus Methanol, Smp. 185-187 . Kellersche Farbreaktion: blau.
EMI0002.0055
(c = 0,5 in 50% Äthanol).
Das als Ausgangssubstanz verwendete d-Lyserg- säurebenzylamid wird hergestellt, indem man d-Lyserg- säurehydrazid mit salpetriger Säure in das Azid über führt und dieses mit Benzylamin umsetzt.
d-Lysergsäurebenzylamid: Smp. 177 .
EMI0002.0064
(c --_ 0,4 in Pyridin). <I>Beispiel 3</I> 1-Methyl-9,10-dihydro-D-lysergsäure-piperidid In analoger Weise wie in Beispiel 1 beschrie ben, wird aus 9,10-Dihydro-D-lysergsäure-piperidid (Smp. 197 ) und Methyljodid das 1-Methyl-9,10- dihydro-D-lysergsäure-piperdid hergestellt.
Bimaleinat: Nadeln aus Athanol. Smp. 201-203 .
EMI0002.0077
(c = 0,5 in 50% Äthanol). Kellersche Farbreaktion: blau.
<I>Beispiel 4</I> 1-Methyl-9,10-dihydro-D-lysergsäure- cyclopentylamid In analoger Weise wie in Beispiel 1 beschrieben, wird aus 9,10-Dihydro-D-lysergsäure-cyclopentylamid (Smp. 228-229 ) und Methyljodid die gewünschte Verbindung hergestellt.
Smp. 248-249 , Prismen aus Essigsäureäthyl- ester.
EMI0002.0093
(c - 0,5 in Pyridin). Kellersche Farbreaktion: blau.
Process for the preparation of derivatives of the lysergic acid series substituted on the indole nitrogen It has been found that derivatives of the lysergic acid series and the dihydrolysergic acid series of the general formula substituted on the indole nitrogen
EMI0001.0007
mel <SEP> I, <SEP> C <SEP> 0-R1
<tb> N <SEP> -C <SEP> H3
<tb> I.
<tb> N
<tb> R2 where R1 is the cyclopentylamino,
denotes the benzylamino or the 1-piperidino radical and R2 denotes an alkyl or aralkyl group and
EMI0001.0016
for grouping
EMI0001.0018
stands, can reach,
by using derivatives of the lysergic acid series or the dihydrolysergic acid series of the general formula 1I
EMI0001.0022
in liquid ammonia with an alkali amide and the resulting alkali salt in the same solvent with an organic halogen compound of the general formula III, Hal-R. III in which Hal stands for bromine or iodine.
The practical implementation of the method ge stalts, for example, so that the alkali amide in the reaction solution itself is prepared by dissolving an alkali metal, preferably sodium or potassium, in liquid ammonia, and this solution, for. B.
by adding ferric nitrate, oxidized. A lysergic acid or dihydrolysergic acid derivative of the formula II is then added and the mixture is mixed with the desired organic halogen compound of the formula III a short time after the solution has taken place. In the case of the derivatives of lysergic acid itself, both the alkali amide and the organic halogen compound are only used to a small extent to avoid side reactions,
At most a twofold excess is used, while with the derivatives of dihydrolysergic acid a larger excess, e.g. B. up to ten times, may be used.
For work-up, the ammonia is evaporated and the residue in a binary solvent system, eg. B. chloroform-water, 'added with shaking. The base mixture remaining after evaporation of the chloroform is optionally chromatographed on aluminum oxide and the desired end product is purified by crystallization.
The derivatives of the lysergic acid and dihydrolysergic acid series prepared according to the invention are in part very nicely crystallized compounds at room temperature which form water-soluble, crystallized, stable salts with suitable acids. They give positive color reactions with Keller's color reagent.
The compounds produced by the present process are distinguished by a strong serotonin-inhibiting effect. They are therefore suitable for therapeutic use in arthritic, allergic and inflammatory phenomena. In addition, the clinical use of the compounds is indicated in those cases in which the formation of serotonin by the enterochromaffin system (carcinoid syndrome) is abnormally increased.
Since serotonin is a physiological active ingredient that occurs in a wide variety of organs and especially in the brain, the compounds are also suitable for the treatment of mental illnesses.
The compounds of the formula II which are used as starting substances and in which R1 is the cyclopentylamino or benzylamino group or the 1-piperidino radical are, for. B. prepared by adding a lysergic acid or dihydrolysergic acid hydrazide of the general formula IV,
EMI0002.0020
where has the same meaning as in formula 1I,
EMI0002.0022
converted with nitrous acid into the azide and this reacts with the desired amine.
In the following examples, all temperatures are given in degrees Celsius. The melting points are not corrected.
<I> Example 1 </I> 1-methyl-d-lysergic acid cyclopentylamide 0.136 g sodium is dissolved in 40 cm3 of liquid ammonia, oxidized with ferric nitrate to form sodium amide, and 0.8 g d-lysergic acid cyclopentylamide is then added to the decolorized solution while stirring [M.p. 121-122 (dec.)] To. After 10 minutes, 0.75 cm33 of methyl iodide is added to the solution.
After a further 10 minutes, the ammonia is evaporated, the residue is shaken between water and chloroform and the crude product obtained after evaporation of the chloroform is crystallized from ethyl acetate.
Rhombic plates of m.p. 163-165. Keller's color reaction: blue.
EMI0002.0042
(c = 0.5 in pyridine). <I> Example 2 </I> 1-Methyl-d-lysergic acid benzylamide In a manner analogous to that described in Example 1, 1-methyl-d-lysergic acid benzylamide is prepared by reacting d-lysergic acid benzylamide with methyl iodide and then ins Bimaleate converted to 1-methyl-d-lysergic acid benzylamide:
Methanol needles, m.p. 185-187. Keller's color reaction: blue.
EMI0002.0055
(c = 0.5 in 50% ethanol).
The d-lysergic acid benzylamide used as the starting substance is produced by converting d-lysergic acid hydrazide with nitrous acid into the azide and reacting this with benzylamine.
d-Lysergic acid benzylamide: m.p. 177.
EMI0002.0064
(c - 0.4 in pyridine). <I> Example 3 </I> 1-Methyl-9,10-dihydro-D-lysergic acid piperidide In a manner analogous to that described in Example 1, 9,10-dihydro-D-lysergic acid piperidide (mp. 197) and methyl iodide produced 1-methyl-9,10-dihydro-D-lysergic acid piperdide.
Bimaleinat: needles made from ethanol. M.p. 201-203.
EMI0002.0077
(c = 0.5 in 50% ethanol). Keller's color reaction: blue.
<I> Example 4 </I> 1-Methyl-9,10-dihydro-D-lysergic acid cyclopentylamide In a manner analogous to that described in Example 1, 9,10-dihydro-D-lysergic acid cyclopentylamide (melting point 228 -229) and methyl iodide produced the desired compound.
Mp. 248-249, prisms made from ethyl acetate.
EMI0002.0093
(c - 0.5 in pyridine). Keller's color reaction: blue.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH197061A CH386441A (en) | 1961-02-17 | 1961-02-17 | Process for the preparation of derivatives of the lysergic acid series substituted on the indole nitrogen |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH197061A CH386441A (en) | 1961-02-17 | 1961-02-17 | Process for the preparation of derivatives of the lysergic acid series substituted on the indole nitrogen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH386441A true CH386441A (en) | 1965-01-15 |
Family
ID=4222862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH197061A CH386441A (en) | 1961-02-17 | 1961-02-17 | Process for the preparation of derivatives of the lysergic acid series substituted on the indole nitrogen |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH386441A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0296748A1 (en) * | 1987-06-15 | 1988-12-28 | Eli Lilly And Company | Cycloalkylamides of (8Beta)-1-alkyl-6-(substituted) ergolines |
| US4931447A (en) * | 1987-06-15 | 1990-06-05 | Eli Lilly And Company | Cycloalkylamides of (8β)-1-alkyl-6-(substituted) ergolines |
| US4981859A (en) * | 1987-06-15 | 1991-01-01 | Cycloalkylamides of (8 beta )-1-alkyl-6-(substituted)ergolines |
-
1961
- 1961-02-17 CH CH197061A patent/CH386441A/en unknown
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0296748A1 (en) * | 1987-06-15 | 1988-12-28 | Eli Lilly And Company | Cycloalkylamides of (8Beta)-1-alkyl-6-(substituted) ergolines |
| US4931447A (en) * | 1987-06-15 | 1990-06-05 | Eli Lilly And Company | Cycloalkylamides of (8β)-1-alkyl-6-(substituted) ergolines |
| US4981859A (en) * | 1987-06-15 | 1991-01-01 | Cycloalkylamides of (8 beta )-1-alkyl-6-(substituted)ergolines | |
| AU613641B2 (en) * | 1987-06-15 | 1991-08-08 | Eli Lilly And Company | Cycloalkylamides of (8beta)-1-isopropyl-6-(substituted) ergolines |
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