CH370417A - Process for the production of new pyrazoles - Google Patents
Process for the production of new pyrazolesInfo
- Publication number
- CH370417A CH370417A CH6695958A CH6695958A CH370417A CH 370417 A CH370417 A CH 370417A CH 6695958 A CH6695958 A CH 6695958A CH 6695958 A CH6695958 A CH 6695958A CH 370417 A CH370417 A CH 370417A
- Authority
- CH
- Switzerland
- Prior art keywords
- cyano
- amino
- ethyl
- pyrazoles
- production
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 10
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000003217 pyrazoles Chemical class 0.000 title description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 230000002140 halogenating effect Effects 0.000 claims description 2
- 150000003254 radicals Chemical group 0.000 claims description 2
- 239000012320 chlorinating reagent Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- FOZZJAVSCUBGPM-UHFFFAOYSA-N 5-amino-1-(2-hydroxyethyl)pyrazole-4-carbonitrile Chemical compound NC1=C(C#N)C=NN1CCO FOZZJAVSCUBGPM-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 230000001914 calming effect Effects 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 1
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical class C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 1
- KGIWPGKKIFFMKP-UHFFFAOYSA-N 2-(ethoxymethylidene)-3-hydroxybutanedinitrile Chemical compound CCOC=C(C#N)C(O)C#N KGIWPGKKIFFMKP-UHFFFAOYSA-N 0.000 description 1
- GQOILBFEHZOUGT-UHFFFAOYSA-N 7h-pyrazolo[3,4-d]triazine Chemical class N1N=NC=C2C=NN=C21 GQOILBFEHZOUGT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 150000003938 benzyl alcohols Chemical class 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- -1 β-hydroxyethyl Chemical group 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung neuer Pyrazole Gegenstand der Erfindung ist ein Verfahren zur Herstellung der neuen Amino-pyrazole der Formel
EMI0001.0003
In dieser Formel bedeutet Hal ein Halogen, vor allem Chlor.
Die neuen Verbindungen zeichnen sich durch eine beruhigende Wirkung aus und können als Heil mittel, vor allem als Tranquilizer, verwendet werden. Sie sind ferner wertvolle Zwischenprodukte für die Herstellung von Heilmitteln, vor allem solcher der Pyrazolo[3,4-d]pyrimidinreihe oder der Pyrazolo- [3,4-d]triazinreihe.
Besonders wertvolle beruhigende Wirkungen zeigt das 2 - (ss - Chlor - äthyl)-3-amino-4-cyan-pyrazol der Formel
EMI0001.0013
Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man in 2-(ss-R-Äthyl)-3-amino- 4-cyan-pyrazolen, worin R einen gegen ein Halogen austauschbaren Rest bedeutet, diesen gegen ein Ha logen austauscht.
So geht man vorzugsweise von 2-(ss-Hydroxy-äthyl)-3-amino-4-cyan-pyrazol aus und behandelt es mit halogenierenden Mitteln, zweck mässig mit Säurehalogeniden des Schwefels oder Phosphors, vor allem Thionylchlorid, Phosphoroxy- chlorid oder Phosphorpentachlorid.
Die Ausgangsstoffe sind bekannt oder lassen sich nach an sich bekannten Methoden herstellen. Sie können auch unter den Reaktionsbedingungen gebildet werden.
Die erfindungsgemäss erhaltenen neuen Verbin dungen können in Form pharmazeutischer Präparate Verwendung finden. Diese enthalten die genannten Verbindungen z. B. in Mischung mit einem für die enterale oder parenterale Applikation geeigneten pharmazeutischen organischen oder anorganischen Trägermaterial. Für dasselbe kommen solche Stoffe in Frage, die mit den beschriebenen Verbindungen nicht reagieren, wie z. B. Wasser, Gelatine, Milch zucker, Stärke, Magnesiumstearat, Talk, pflanzliche Öle, Benzylalkohole, Gummi, Polyalkylenglykole, Cholesterin oder andere bekannte Arzneimittelträger.
Die pharmazeutischen Präparate können z. B. als Tabletten oder Dragees, oder in flüssiger Form als Lösungen, Suspensionen oder Emulsionen, vorlie gen. Gegebenenfalls sind sie sterilisiert und bzw. oder enthalten Hilfsstoffe, wie Konservierungs-, Stabilisie- rungs-, Netz- oder Emulgiermittel. Sie können auch noch andere therapeutisch wertvolle Stoffe enthalten. Die Präparate können nach üblichen Methoden ge wonnen werden.
Die Temperaturen sind im folgenden Beispiel in Celsiusgraden angegeben.
<I>Beispiel</I> Eine Lösung von 15,2 g 2-(ss-Hydroxy-äthyl)-3- amino-4-cyan-pyrazol in 150 cms Thionylehlorid wird während 2 Stunden auf 50-60 erhitzt. Man dampft im Vakuum vom Thionylchlorid ab, ver setzt den Rückstand mit Eis-Wasser und stellt mit In Natronlauge auf pH B.
Es wird hernach von dem ausgefallenen Niederschlag abgenutscht und dieser aus Äthanol umkristallisiert. 2 - (ss - Chlor - äthyl)-3- amino-4-cyan pyrazol der Formel
EMI0002.0009
wird so in gelben Kristallen vom F. 154-155 er halten.
Das als Ausgangsprodukt verwendete 2-(ss-Hy- droxy-äthyl)-3-amino-4-cyan-pyrazol kann auf fol gendem Wege hergestellt werden: Eine Lösung von 48,8g Äthoxymethylen-malo- nitril in 500 cm3 Äthanol wird mit 44 g 70o/oigem (ss-Hydroxy-äthyl)-hydrazin versetzt.
Man erhitzt dann das Reaktionsgemisch während 10 Stunden am Rückfluss, dampft im Vakuum zur Trockne und kristallisiert aus wenig Äthanol. 2-(ss-Hydroxy-äthyl)- 3-amino-4-cyan-pyrazol der Formel
EMI0002.0022
wird so in gelben Kristallen vom F. 156-158 er halten.
Process for the preparation of new pyrazoles The invention relates to a process for the preparation of the new aminopyrazoles of the formula
EMI0001.0003
In this formula, Hal means a halogen, especially chlorine.
The new compounds are characterized by a calming effect and can be used as medicinal products, especially as tranquilizers. They are also valuable intermediate products for the production of medicaments, especially those of the pyrazolo [3,4-d] pyrimidine series or the pyrazolo [3,4-d] triazine series.
The 2 - (ss - chloro - ethyl) -3-amino-4-cyano-pyrazole of the formula shows particularly valuable calming effects
EMI0001.0013
The process according to the invention is characterized in that in 2- (ss-R-ethyl) -3-amino-4-cyano-pyrazoles, in which R denotes a radical which can be exchanged for a halogen, this is exchanged for a halogen.
So one preferably starts from 2- (β-hydroxyethyl) -3-amino-4-cyano-pyrazole and treats it with halogenating agents, advantageously with acid halides of sulfur or phosphorus, especially thionyl chloride, phosphorus oxychloride or phosphorus pentachloride .
The starting materials are known or can be produced by methods known per se. They can also be formed under the reaction conditions.
The new compounds obtained according to the invention can be used in the form of pharmaceutical preparations. These contain the compounds mentioned z. B. in a mixture with a pharmaceutical, organic or inorganic carrier material suitable for enteral or parenteral administration. For the same substances come into question that do not react with the compounds described, such as. B. water, gelatin, milk sugar, starch, magnesium stearate, talc, vegetable oils, benzyl alcohols, gum, polyalkylene glycols, cholesterol or other known excipients.
The pharmaceutical preparations can e.g. B. as tablets or dragees, or in liquid form as solutions, suspensions or emulsions, are present. If necessary, they are sterilized and / or contain auxiliaries such as preservatives, stabilizers, wetting agents or emulsifiers. They can also contain other therapeutically valuable substances. The preparations can be obtained by customary methods.
In the following example, the temperatures are given in degrees Celsius.
<I> Example </I> A solution of 15.2 g of 2- (ss-hydroxyethyl) -3-amino-4-cyano-pyrazole in 150 cms of thionyl chloride is heated to 50-60 for 2 hours. Thionyl chloride is evaporated in vacuo, the residue is added to ice-water and the pH is adjusted to B with sodium hydroxide solution.
The precipitate is then filtered off with suction and this is recrystallized from ethanol. 2 - (ss - chlorine - ethyl) -3-amino-4-cyano pyrazole of the formula
EMI0002.0009
is kept in yellow crystals from F. 154-155.
The 2- (ss-hydroxy-ethyl) -3-amino-4-cyano-pyrazole used as the starting product can be produced in the following way: A solution of 48.8 g of ethoxymethylene malonitrile in 500 cm3 of ethanol is mixed with 44 g of 70% (β-hydroxyethyl) hydrazine were added.
The reaction mixture is then refluxed for 10 hours, evaporated to dryness in vacuo and crystallized from a little ethanol. 2- (β-hydroxy-ethyl) -3-amino-4-cyano-pyrazole of the formula
EMI0002.0022
is kept in yellow crystals from F. 156-158.
Claims (1)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH6695958A CH370417A (en) | 1958-12-05 | 1958-12-05 | Process for the production of new pyrazoles |
| DE1959C0020247 DE1162375B (en) | 1958-12-05 | 1959-11-26 | Process for the preparation of 1- (beta-chloroethyl) -4-cyano-5-amino-pyrazole. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH6695958A CH370417A (en) | 1958-12-05 | 1958-12-05 | Process for the production of new pyrazoles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH370417A true CH370417A (en) | 1963-07-15 |
Family
ID=4527568
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH6695958A CH370417A (en) | 1958-12-05 | 1958-12-05 | Process for the production of new pyrazoles |
Country Status (2)
| Country | Link |
|---|---|
| CH (1) | CH370417A (en) |
| DE (1) | DE1162375B (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT170882B (en) * | 1950-02-13 | 1952-04-10 | Ciba Geigy | Process for the preparation of new 3-amino-5-halopyrazoles |
-
1958
- 1958-12-05 CH CH6695958A patent/CH370417A/en unknown
-
1959
- 1959-11-26 DE DE1959C0020247 patent/DE1162375B/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DE1162375B (en) | 1964-02-06 |
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