CH366551A - Process for the production of new triazines - Google Patents
Process for the production of new triazinesInfo
- Publication number
- CH366551A CH366551A CH1439260A CH1439260A CH366551A CH 366551 A CH366551 A CH 366551A CH 1439260 A CH1439260 A CH 1439260A CH 1439260 A CH1439260 A CH 1439260A CH 366551 A CH366551 A CH 366551A
- Authority
- CH
- Switzerland
- Prior art keywords
- acid
- triazines
- phenyl
- production
- new
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 10
- 150000003918 triazines Chemical class 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- -1 aliphatic alcohols Chemical class 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 150000001350 alkyl halides Chemical class 0.000 claims 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000013078 crystal Substances 0.000 description 5
- BVUUZKZVRGBSFN-UHFFFAOYSA-N C1(=CC=CC=C1)N1N=NC(=C2C1=NN=C2)O Chemical compound C1(=CC=CC=C1)N1N=NC(=C2C1=NN=C2)O BVUUZKZVRGBSFN-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- MAKQREKUUHPPIS-UHFFFAOYSA-N 5-amino-1-phenyl-1H-pyrazole-4-carbonitrile Chemical compound NC1=C(C#N)C=NN1C1=CC=CC=C1 MAKQREKUUHPPIS-UHFFFAOYSA-N 0.000 description 2
- UBKSUPKIDNXMMC-UHFFFAOYSA-N 5-amino-1-phenylpyrazole-4-carboxamide Chemical compound NC1=C(C(=O)N)C=NN1C1=CC=CC=C1 UBKSUPKIDNXMMC-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 150000005840 aryl radicals Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 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
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 150000003842 bromide salts Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 235000015165 citric acid Nutrition 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
- 238000000354 decomposition reaction Methods 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung neuer Triazine Gegenstand der Erfindung ist ein Verfahren zur Herstellung von v-Triazinen, die einer der Formeln
EMI0001.0005
entsprechen, worin R einen aliphatischen Rest und Ar einen Arylrest bedeutet.
In den neuen Verbindungen ist der Arylrest vor zugsweise ein unsubstitu.ierter oder substituierter, z. B. ein Halogen-, Alkoxy- oder Alkyl-substituierter Phe- nylrest. Der aliphatische Rest am Heteroatom ist vorzugsweise ein niederer Kohlenwasserstoffrest, in dem ein nicht an das Heteroatom gebundenes Koh- lenstoffatom auch durch ein Heteroatom, wie Stick stoff, ersetzt sein kann, z.
B. ein Alkylaminoalkyl- rest, wie Dimethylaminoäthyl, vor allem aber ein niederer Alkylrest, wie Methyl.
Die neuen v-Triazine besitzen wertvolle pharma kologische Eigenschaften, so dass sie als Heilmittel Verwendung finden können. Insbesondere sind sie durch eine diuretische Wirkung ausgezeichnet und können dementsprechend als Diuretika verwendet werden. Ausserdem sind sie wertvo'll'e Zwischen produkte für die Herstellung von Heilmitteln.
Das erfindungsgemässe Verfahren zur Herstellung der neuen Verbindungen ist dadurch gekennzeichnet, dass man 1-Aryl-4-hydroxy-pyrazolo[3,4-d]v-triazine mit reaktionsfähigen Estern von aliphatischen Alko holen, gegebenenfalls in Gegenwart von Kondensa- tionsmitteln, wie Alkalien oder Metallalkoholaten um setzt. Als reaktionsfähige Ester kommen insbesondere solche starker anorganischer oder organischer Säu ren, wie z.
B. der Halogenwasserstoffsäure, Schwefel säure oder organischer Sulfonsäuren, z. B. Benzol- sulfonsäuren, in Betracht. In erster Linie werden nie dere Alkyl- oder Dialkylaminoalkyl-halogenide, wie z. B. deren Chloride, Bromide oder Jod'ide verwendet.
Die Ausgangsstoffe können nach dem Verfahren gemäss Schweiz. Patentschrift Nr. 365730 erhalten worden.
Die neuen Verbindungen werden je nach den Reaktionsbedingungen in Form der freien Verbindun gen oder ihrer Salze erhalten, die in üblicher Weise ineinander übergeführt werden können. So lassen sich freie Basen in ihre Salze umwandeln, z.
B. durch Umsetzung mit anorganischen oder organischen Säu ren, wie Halogenwasserstoffsäuren, Schwefelsäure, Salpetersäure, Perchlorsäure, Phosphorsäuren, Amei sensäure, Essigsäure, Propionsäure, Milchsäure, Oxal- säure, Bernsteinsäure, Äpfelsäure, Weinsäure, Zitro nensäure, Ascorbinsäure, Methansulfonsäure, Äthan- sulfonsäure, Oxyäthansulfonsäure,
Benzoesäure, Sali- cyl'säure, p-Aminosalicylsäure, Toluolsulfonsäure oder Naphthalinsufonsäuren.
In den nachfolgenden Beispielen sind die Tem peraturen in Celsiusgraden angegeben. <I>Beispiel 1</I> In eine Natriummethylat-Lösung, hergestellt aus 1,2 g Natrium und 400 cms wasserfreiem Alkohol, werden 10,6 g 1-Phenyl-4-hydroxy-pyrazolo[3,4-d]v- triazin eingetragen. Zur Bildung des Natriumsalzes wird während 3 Stunden bei Zimmertemperatur ge rührt.
Man versetzt die gebildete Suspension mit 7,2 g Chloräthyldimethylamin, erhitzt während 6 Stunden zum Sieden, dampft dann im Vakuum zur Trockne ein, löst den Rückstand in Wasser und extrahiert mit Chloroform. Der Chloroformrückstand wird aus Isopropyläther umkristallisiert und so 1 Phenyl-4-hydroxy-pyrazolo[3,4-d]v-triazin, dessen tautomerisierbares Wasserstoffatom durch den Di- methylaminoäthylrest ersetzt ist, in Kristallen vom F. 103-105 erhalten.
Das als Ausgangsstoff zu verwendende 1-Phenyl- 4-hydroxy-pyrazolo[3,4-d]v-triazin kann wie folgt er halten werden: 24,4 g Äthoxymethylenmalonsäure-dinitril wer den in 250 cm3 Äthylalkohol gelöst. Die Lösung wird dann langsam mit 22 g Phenylhydrazin versetzt und während 10 Stunden zum Sieden erhitzt. Man lässt erkalten, wonach ein kristallines Produkt ausfällt, von dem abgenutscht wird.
Durch nochmalige Kri- stallisation aus Alkohol erhält man 2-Phenyl-3-amino- 4-cyan-pyrazol der Formel
EMI0002.0022
in Kristallen vom F. 135-137 .
Dieses Produkt kann wie folgt in das entspre chende Amid übergeführt werden: Zu einer Lösung von 5 g 2-Phenyl-3-amino-4- cyan-pyrazol in 100 cm3 Alkohol werden 100 cm3 2-n. Natronlauge gegeben, und es wird während 3 Stunden zum Sieden erhitzt. Man dampft hierauf im Vakuum den Alkohol ab, wobei ein festes Pro dukt ausfällt. Letzteres wird aus Alkohol umkristalli siert und so 2-Phenyl-3-amino-4-carbamyl-pyrazol der Formel
EMI0002.0031
in Kristallen vom F. 167-168 erhalten.
Eine _ Lösung von 20 g 2-Phenyl-3-amino-4- carbamyl-pyrazol in 150 cm3 2-n. Salzsäure wird bei 0-10 mit 6,9 g Natriumnitrit gelöst in 40 cm3 Was ser versetzt, wobei sich ein gelber Niederschlag ab scheidet. Zur Vervollständigung der Reaktion rührt man noch während zwei Stunden bei Zimmertempe ratur, nutscht dann von dem ausgefallenen Produkt ab und wäscht mit Wasser nach.
Es wird aus Alkohol umkristallisiert und so 1-Phenyl-4-hydroxy- pyrazolo[3,4-d]v-triazin der Formel
EMI0002.0046
in gelblichen Kristallen vom F. l36 (unter Zer setzung) erhalten.
<I>Beispiel 2</I> Eine Lösung von 10 g 1-Phenyl-4-hydroxy-pyra- zolo[3,4-d]v-triazin in 50 cm3 2-n. Natronlauge wird unter Rühren und Eiskühlung mit 7,4 g Dimethyl- sulfat versetzt.
Man lässt während 5 Stunden bei Zimmertemperatur stehen und nutscht dann von dem ausgefallenen Niederschlag ab. Letzterer wird aus viel Petroläther umkristallisiert und so 1-Phenyl-4- hydroxy-pyrazolo-[3,4-d]v-triazin, dessen tautomeri- sierbares Wasserstoffatom durch die Methylgruppe ersetzt ist, in weissen Kristallen vom F. 136-137 erhalten.
Process for the preparation of new triazines The invention relates to a process for the preparation of v-triazines which have one of the formulas
EMI0001.0005
correspond, where R is an aliphatic radical and Ar is an aryl radical.
In the new compounds, the aryl radical is preferably an unsubstitu.ierter or substituted, z. B. a halogen, alkoxy or alkyl-substituted phenyl radical. The aliphatic radical on the heteroatom is preferably a lower hydrocarbon radical in which a carbon atom not bonded to the heteroatom can also be replaced by a heteroatom, such as nitrogen, e.g.
B. an alkylaminoalkyl radical such as dimethylaminoethyl, but above all a lower alkyl radical such as methyl.
The new v-triazines have valuable pharmacological properties so that they can be used as remedies. In particular, they are excellent in a diuretic effect and accordingly can be used as diuretics. They are also valuable intermediate products for the manufacture of medicinal products.
The inventive method for the preparation of the new compounds is characterized in that 1-aryl-4-hydroxy-pyrazolo [3,4-d] v-triazines with reactive esters of aliphatic alcohols, optionally in the presence of condensation agents such as Alkalis or metal alcoholates. As reactive esters come in particular those strong inorganic or organic acids such.
B. the hydrohalic acid, sulfuric acid or organic sulfonic acids, z. B. benzene sulfonic acids into consideration. First and foremost, never more alkyl or dialkylaminoalkyl halides, such as. B. used their chlorides, bromides or Jod'ide.
The starting materials can be processed according to the Swiss procedure Patent No. 365730 has been obtained.
Depending on the reaction conditions, the new compounds are obtained in the form of the free compounds or their salts, which can be converted into one another in a customary manner. Free bases can be converted into their salts, e.g.
B. through reaction with inorganic or organic acids, such as hydrohalic acids, sulfuric acid, nitric acid, perchloric acid, phosphoric acids, formic acid, acetic acid, propionic acid, lactic acid, oxalic acid, succinic acid, malic acid, tartaric acid, citric acid, ascorbic acid, methanesulfonic acid, ethane sulfonic acid, oxyethanesulfonic acid,
Benzoic acid, salicylic acid, p-aminosalicylic acid, toluenesulfonic acid or naphthalenesulfonic acids.
In the following examples, the temperatures are given in degrees Celsius. <I> Example 1 </I> 10.6 g of 1-phenyl-4-hydroxypyrazolo [3,4-d] v. Are added to a sodium methylate solution prepared from 1.2 g of sodium and 400 cms of anhydrous alcohol - registered triazine. To form the sodium salt, the mixture is stirred at room temperature for 3 hours.
The suspension formed is mixed with 7.2 g of chloroethyldimethylamine, heated to boiling for 6 hours, then evaporated to dryness in vacuo, the residue is dissolved in water and extracted with chloroform. The chloroform residue is recrystallized from isopropyl ether and 1 phenyl-4-hydroxy-pyrazolo [3,4-d] v-triazine, the tautomerizable hydrogen atom of which has been replaced by the dimethylaminoethyl radical, is obtained in crystals with a melting point of 103-105.
The 1-phenyl-4-hydroxy-pyrazolo [3,4-d] v-triazine to be used as the starting material can be obtained as follows: 24.4 g ethoxymethylene malonic acid dinitrile are dissolved in 250 cm3 of ethyl alcohol. The solution is then slowly mixed with 22 g of phenylhydrazine and heated to boiling for 10 hours. It is allowed to cool, after which a crystalline product precipitates and is filtered off with suction.
Another crystallization from alcohol gives 2-phenyl-3-amino-4-cyano-pyrazole of the formula
EMI0002.0022
in crystals from F. 135-137.
This product can be converted into the corresponding amide as follows: To a solution of 5 g of 2-phenyl-3-amino-4-cyano-pyrazole in 100 cm3 of alcohol add 100 cm3 of 2-n. Added sodium hydroxide solution, and it is heated to boiling for 3 hours. The alcohol is then evaporated in vacuo, a solid product precipitating out. The latter is recrystallized from alcohol and so 2-phenyl-3-amino-4-carbamyl-pyrazole of the formula
EMI0002.0031
preserved in crystals from F. 167-168.
A solution of 20 g of 2-phenyl-3-amino-4-carbamyl-pyrazole in 150 cm3 of 2-n. Hydrochloric acid is mixed with 6.9 g of sodium nitrite dissolved in 40 cm3 of water at 0-10, a yellow precipitate separating out. To complete the reaction, the mixture is stirred for two hours at room temperature, then the precipitated product is suction filtered and washed with water.
It is recrystallized from alcohol to give 1-phenyl-4-hydroxypyrazolo [3,4-d] v-triazine of the formula
EMI0002.0046
obtained in yellowish crystals from F. 136 (with decomposition).
<I> Example 2 </I> A solution of 10 g of 1-phenyl-4-hydroxy-pyrazolo [3,4-d] v-triazine in 50 cm3 of 2-n. Sodium hydroxide solution is admixed with 7.4 g of dimethyl sulfate while stirring and cooling with ice.
The mixture is left to stand for 5 hours at room temperature and the precipitate which has separated out is then suction filtered. The latter is recrystallized from a lot of petroleum ether and so 1-phenyl-4-hydroxy-pyrazolo- [3,4-d] v-triazine, whose tautomerizable hydrogen atom has been replaced by the methyl group, is obtained in white crystals with a melting point of 136-137 .
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1439260A CH366551A (en) | 1957-01-14 | 1957-01-14 | Process for the production of new triazines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1439260A CH366551A (en) | 1957-01-14 | 1957-01-14 | Process for the production of new triazines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH366551A true CH366551A (en) | 1963-01-15 |
Family
ID=4400425
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1439260A CH366551A (en) | 1957-01-14 | 1957-01-14 | Process for the production of new triazines |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH366551A (en) |
-
1957
- 1957-01-14 CH CH1439260A patent/CH366551A/en unknown
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