CH297727A - Process for the preparation of a new disubstituted nicotinic acid amide. - Google Patents
Process for the preparation of a new disubstituted nicotinic acid amide.Info
- Publication number
- CH297727A CH297727A CH297727DA CH297727A CH 297727 A CH297727 A CH 297727A CH 297727D A CH297727D A CH 297727DA CH 297727 A CH297727 A CH 297727A
- Authority
- CH
- Switzerland
- Prior art keywords
- nicotinic acid
- amide
- preparation
- acid amide
- ethyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 4
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical class NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 title claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- -1 1,2-diphenyl-ethyl Chemical group 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 4
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 230000002921 anti-spasmodic effect Effects 0.000 claims description 2
- 239000000812 cholinergic antagonist Substances 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000013067 intermediate product Substances 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- DWODOIKZDGJOPQ-UHFFFAOYSA-N Nicofetamide Chemical compound C=1C=CN=CC=1C(=O)NC(C=1C=CC=CC=1)CC1=CC=CC=C1 DWODOIKZDGJOPQ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 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 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Classifications
-
- 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
- C07D213/60—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 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 ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Description
Verfahren zur Herstellung eines neuen disubstituierten Nicotinsäureamids. Gegenstand der Erfindung ist ein Verfah ren zur Herstellung eines neuen disubstituier- l en \ icotinsäur eamids der Formel
EMI0001.0007
welches dadureh gekennzeichnet ist, dass man einen reaktionsfähigen Ester des Alkohols der f orlllel
EMI0001.0013
mit einer den Rest
EMI0001.0014
liefernden Verbindung umsetzt.
Als reaktionsfähige Ester des Alkohols I 1;a1111 Inall beispielsweise einen Halogenwasser- stoffsäure-, einen Schwefelsäure-, einen Alkyl- bzw. Arylsulfonsäureester verwenden. Statt des freien Aminoalkoholesters kann auch ein Salz eines solchen zur Reaktion gebracht wer den.
Vorteilhaft verwendet man als den Rest II liefernde Verbindung ein N-Metallderivat des II entsprechenden Amids. Man kann aber auch das freie Amid II unter Zuhilfenahme eines Metallamids als Kondensationsmittel mit einem reaktionsfähigen Aminoalkoholester zur Reak tion bringen.
Das so erhaltene Nicotinsäure-N-(1,2-di- phenyl- äthy 1)-N- (y-2,6 - dimethyl-piperidino- propyl)-amid löst. sich gut in verdünnten Säu ren, wenig in Wasser und Petroläther. Die neue Verbindung soll als Spasmolytikum und als Zwischenprodukt zur Herstellung weiterer Derivate Verwendung finden.
Beispiel: 15,1g Nicotinsäure-N-(1,2-diphenyl-äthyl)- amid, suspendiert in<B>150</B> ems absol. Benzol, werden mit 2,3 g gepulvertem Natriumamid versetzt und kurze Zeit auf Siedetemperatur erhitzt, wobei eine starke Ammoniakentwick- lung eintritt.
Nachdem die Gasentwicklung nachgelassen hat, lässt man 10,4 g y-2,6-Di- Inethyl - piperidino - propylchlorid, gelöst in 1.50 ems absol. Benzol, zutropfen und rührt dann weitere 10 Stunden unter Rückfluss- kochen. Nach dem Erkalten wird die Lösung vom überschüssigen Natriumamid abdekan- tiert und mit 60 warmer 1,5n-Salzsäure aus- gezogen, bis der Auszug schwach sauer rea giert.
Der noch warme salzsaure Auszug wird mit Kohle filtriert, mit Lauge alkalisiert, er schöpfend ausgeäthert. und der Äther abdestil- liert. Der Rückstand wird im Hochvakuum destilliert, wobei das Nicotinsäure-N-(1,2-di- phenyl - äthyl) -N - (y-2,6- dimethyl - pipesridino- propyl)-amid in guter Ausbeute gewonnen wird.
An Stelle von Natriumamid als Konden sationsmittel, kann man das Nicotinsäure-N- (1,2-diphenyl-äthyl)-amid mit Natrium behan deln und das entstandene Natriumsalz an schliessend mit y-2,6-Dimethyl-piperidino-pro- pylchlorid kondensieren, wobei die gleiche Verbindung in befriedigender Ausbeute und Reinheit gewonnen wird.
Process for the preparation of a new disubstituted nicotinic acid amide. The invention relates to a process for the preparation of a new disubstituted en \ icotinic acid amide of the formula
EMI0001.0007
which is characterized by the fact that one is a reactive ester of the alcohol of the filler
EMI0001.0013
with one the rest
EMI0001.0014
the supplying connection.
Use, for example, a hydrogen halide, a sulfuric acid, an alkyl or aryl sulfonic acid ester as the reactive ester of the alcohol I 1; a1111 Inall. Instead of the free amino alcohol ester, a salt of such can also be made to react.
It is advantageous to use an N-metal derivative of the amide corresponding to II as the compound supplying the radical II. But you can also bring the free amide II with the aid of a metal amide as a condensation agent with a reactive amino alcohol ester to reac tion.
The nicotinic acid-N- (1,2-di-phenyl-ethy 1) -N- (y-2,6-dimethyl-piperidino-propyl) -amide thus obtained dissolves. well in dilute acids, little in water and petroleum ether. The new compound is said to be used as an antispasmodic and as an intermediate for the production of further derivatives.
Example: 15.1g nicotinic acid-N- (1,2-diphenyl-ethyl) - amide, suspended in <B> 150 </B> ems absol. Benzene, 2.3 g of powdered sodium amide are added and the mixture is heated to boiling temperature for a short time, during which time a strong evolution of ammonia occurs.
After the evolution of gas has subsided, 10.4 g of y-2,6-di-ynethyl-piperidino-propyl chloride, dissolved in 1.50 ems absol. Benzene, add dropwise and then stir under reflux for a further 10 hours. After cooling, the solution is decanted from the excess sodium amide and extracted with 60% warm 1.5N hydrochloric acid until the extract reacts slightly acidic.
The still warm hydrochloric acid extract is filtered with charcoal, alkalized with lye, it is extracted with ether. and the ether is distilled off. The residue is distilled in a high vacuum, the nicotinic acid-N- (1,2-diphenyl-ethyl) -N- (y-2,6-dimethyl-pipesridino-propyl) -amide being obtained in good yield.
Instead of sodium amide as a condensation agent, the nicotinic acid-N- (1,2-diphenyl-ethyl) -amide can be treated with sodium and the resulting sodium salt can then be treated with y-2,6-dimethyl-piperidino-propyl chloride condense, the same compound being obtained in satisfactory yield and purity.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH294511T | 1951-03-01 | ||
| CH297727T | 1951-03-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH297727A true CH297727A (en) | 1954-03-31 |
Family
ID=25733488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH297727D CH297727A (en) | 1951-03-01 | 1951-03-01 | Process for the preparation of a new disubstituted nicotinic acid amide. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH297727A (en) |
-
1951
- 1951-03-01 CH CH297727D patent/CH297727A/en unknown
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