CH312530A - Process for making a pyridazone. - Google Patents
Process for making a pyridazone.Info
- Publication number
- CH312530A CH312530A CH312530DA CH312530A CH 312530 A CH312530 A CH 312530A CH 312530D A CH312530D A CH 312530DA CH 312530 A CH312530 A CH 312530A
- Authority
- CH
- Switzerland
- Prior art keywords
- phenyl
- pyridazon
- parts
- water
- pyridazone
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- 230000001419 dependent effect Effects 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000000155 melt Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- -1 methylmercapto group Chemical group 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung eines Pyridazons. Gegenstand des vorliegenden Patentes ist ein Verfahren zur Herstellung von 6 ,-VIorpho- lino-2-phenyl-pyiidazon-(3) der Formel
EMI0001.0004
Die neue Verbindung wird erhalten, wenn man 2-Phenyl-pyridazon-(3), das in 6-Stel- lung einen austauschfähigen Substituenten aufweist, mit Morpholin umsetzt.
Ein aus tausehfähiger Substituent ist zum Beispiel ein Halogen-, insbesondere ein Chloratom, oder auch eine substituierte Oxy-, wie Phenoxy-, oder Mereapto-, wie bTethylmercaptogruppe.
Die Reaktion kann in An- oder Abwesen heit von Verdünnungsmitteln und/oder Kon densationsmitteln undloder Katalysatoren im offenen oder geschlossenen Gefäss unter Druck durchgeführt werden.
Das Verfahrensprodukt, das 6-Morpliolino- 2-phenyl-pyridazon-(3) vom F. =181-183 , ist neu. Es zeigt eine antipyretische und anal- getischeWirkung und soll als Heilmittel Ver wendung finden.
Die Erfindung wird im nachfolgenden Bei spiel. näher beschrieben. Zwischen Gewichts teil und Volumteil besteht die gleiche Bezie- hung wie zwischen Gramm und Kubikzenti meter.
<I>Beispiel:</I> 57 Gewichtsteile 2-Phenyl-6-chlor-pyrid- azon-(3) werden mit 140 Gewichtsteilen Mor- pholin 10 Stunden auf 150 erhitzt. Das Re aktionsgemisch wird in 630 Volumteilen 2n- Salzsäure heiss gelöst und nach dem Erkalten genutscht. Der Rückstand wird in 96o/oigem Äthanol heiss gelöst, die Lösung heiss durch Zugabe von konzentriertem wässerigem Am moniak alkalisch gestellt, über Tierkohle fil triert und mit Wasser versetzt,
worauf in der Kälte das 6-Morpholino-2-phenyl-pyridazon-(3) auskristallisiert und abgenutseht wird. Es schmilzt nach Umkristallisieren aus Äthanol- Wasser bei 181-183 .
Das als Ausgangsstoff verwendete 2-Phe- nyl-6-chlor-pyridazon-(3) kann auf folgende Weise hergestellt werden: 235 Gewichtsteile Maleinsäureanhydrid werden in 2000 Volumteilen Eisessig gelöst. und mit einer Lösung von 270 Gewichtstei len Phenylhydrazin in 500 Volumteilen Eis essig 3 Stunden -unter Rückfluss gekocht. Die heisse Lösung wird dann unter Rühren auf 700 Volumteile Wasser gegossen, wobei Kri stallisation eintritt.
Die gekühlte Mischung wird genutscht, der Rückstand mit Wasser gewaschen, zur Reinigung in ln-Sodalösung gelöst und nach Filtrieren mit 2n-Salzsäure wieder ausgefällt. Der Niederschlag wird ge- nutscht, mit Wasser gewaschen und getrock net.
Das so erhaltene 2-Phenyl-6-oxy-pyrid- azon-(3) schmilzt bei 272-274 . 100 Gewichts teile desselben werden mit 750 Volumteilen Phosphoroxychlorid 1 Stunde auf dem sieden den Wasserbad erhitzt, die Lösung unter Rüh ren vorsichtig auf 5500 Gewichtsteile Eis ge gossen und nach einstündigem Stehen in der Kälte der Niederschlag abgenutscht. Man wäscht ihn mit Wasser und kristallisiert ihn aus Wasser um.
Das so erhaltene 2-Phenyl- 6-ehlor-pyridazon-(3) der Formel
EMI0002.0011
schmilzt bei 116-118 .
Process for making a pyridazone. The present patent is a process for the preparation of 6, -VIorpholino-2-phenyl-pyiidazon- (3) of the formula
EMI0001.0004
The new compound is obtained when 2-phenyl-pyridazon- (3), which has an exchangeable substituent in the 6-position, is reacted with morpholine.
A substituent that can be substituted is, for example, a halogen, especially a chlorine atom, or a substituted oxy, such as phenoxy, or mereapto, such as methylmercapto group.
The reaction can be carried out in the presence or absence of diluents and / or condensation agents and / or catalysts in an open or closed vessel under pressure.
The product of the process, the 6-Morpliolino-2-phenyl-pyridazon- (3) of F. = 181-183, is new. It shows an antipyretic and analgesic effect and is said to be used as a remedy.
The invention is used in the following example. described in more detail. There is the same relationship between the weight part and the volume part as there is between grams and cubic centimeters.
<I> Example: </I> 57 parts by weight of 2-phenyl-6-chloro-pyridazon- (3) are heated to 150 with 140 parts by weight of morpholine for 10 hours. The reaction mixture is dissolved in 630 parts by volume of hot 2N hydrochloric acid and suction filtered after cooling. The residue is dissolved in 96% hot ethanol, the solution is made hot alkaline by adding concentrated aqueous ammonia, filtered over animal charcoal and mixed with water.
whereupon the 6-morpholino-2-phenyl-pyridazon- (3) crystallizes out in the cold and is removed. After recrystallization from ethanol-water, it melts at 181-183.
The 2-phenyl-6-chloropyridazon- (3) used as starting material can be prepared in the following manner: 235 parts by weight of maleic anhydride are dissolved in 2000 parts by volume of glacial acetic acid. and boiled under reflux for 3 hours with a solution of 270 parts by weight of phenylhydrazine in 500 parts by volume of glacial acetic acid. The hot solution is then poured into 700 parts by volume of water with stirring, crystallization occurring.
The cooled mixture is suction filtered, the residue is washed with water, dissolved in 1N soda solution for cleaning and precipitated again after filtration with 2N hydrochloric acid. The precipitate is filtered off with suction, washed with water and dried.
The 2-phenyl-6-oxy-pyridazon- (3) thus obtained melts at 272-274. 100 parts by weight of the same are heated with 750 parts by volume of phosphorus oxychloride for 1 hour on the boiling water bath, the solution is carefully poured onto 5500 parts by weight of ice while stirring and the precipitate is suction filtered after standing in the cold for one hour. It is washed with water and recrystallized from water.
The 2-phenyl-6-chloro-pyridazon- (3) of the formula obtained in this way
EMI0002.0011
melts at 116-118.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH312530T | 1952-06-20 | ||
| CH310245T | 1952-06-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH312530A true CH312530A (en) | 1955-12-31 |
Family
ID=25735638
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH312530D CH312530A (en) | 1952-06-20 | 1952-06-20 | Process for making a pyridazone. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH312530A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8304413B2 (en) | 2008-06-03 | 2012-11-06 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| US8741936B2 (en) | 2005-05-10 | 2014-06-03 | Intermune, Inc. | Method of modulating stress-activated protein kinase system |
| US9359379B2 (en) | 2012-10-02 | 2016-06-07 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US10233195B2 (en) | 2014-04-02 | 2019-03-19 | Intermune, Inc. | Anti-fibrotic pyridinones |
-
1952
- 1952-06-20 CH CH312530D patent/CH312530A/en unknown
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10010536B2 (en) | 2005-05-10 | 2018-07-03 | Intermune, Inc. | Method of modulating stress-activated protein kinase system |
| US8741936B2 (en) | 2005-05-10 | 2014-06-03 | Intermune, Inc. | Method of modulating stress-activated protein kinase system |
| US9527816B2 (en) | 2005-05-10 | 2016-12-27 | Intermune, Inc. | Method of modulating stress-activated protein kinase system |
| US8969347B2 (en) | 2008-06-03 | 2015-03-03 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| US9290450B2 (en) | 2008-06-03 | 2016-03-22 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| USRE47142E1 (en) | 2008-06-03 | 2018-11-27 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| US8304413B2 (en) | 2008-06-03 | 2012-11-06 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| US9675593B2 (en) | 2012-10-02 | 2017-06-13 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US9359379B2 (en) | 2012-10-02 | 2016-06-07 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US10376497B2 (en) | 2012-10-02 | 2019-08-13 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US10898474B2 (en) | 2012-10-02 | 2021-01-26 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US10233195B2 (en) | 2014-04-02 | 2019-03-19 | Intermune, Inc. | Anti-fibrotic pyridinones |
| US10544161B2 (en) | 2014-04-02 | 2020-01-28 | Intermune, Inc. | Anti-fibrotic pyridinones |
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