DE1200309B - Process for the preparation of 4- (3, 4,5-trimethoxybenzoylamido) -1-phenyl-2, 3-dimethylpyrazolone- (5) - Google Patents
Process for the preparation of 4- (3, 4,5-trimethoxybenzoylamido) -1-phenyl-2, 3-dimethylpyrazolone- (5)Info
- Publication number
- DE1200309B DE1200309B DEK44970A DEK0044970A DE1200309B DE 1200309 B DE1200309 B DE 1200309B DE K44970 A DEK44970 A DE K44970A DE K0044970 A DEK0044970 A DE K0044970A DE 1200309 B DE1200309 B DE 1200309B
- Authority
- DE
- Germany
- Prior art keywords
- phenyl
- trimethoxybenzoylamido
- dimethyl
- dimethylpyrazolone
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 13
- 238000002360 preparation method Methods 0.000 title claims description 4
- SJSOFNCYXJUNBT-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC(OC)=C1OC SJSOFNCYXJUNBT-UHFFFAOYSA-N 0.000 claims description 10
- IWPZKOJSYQZABD-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid Natural products COC1=CC(OC)=CC(C(O)=O)=C1 IWPZKOJSYQZABD-UHFFFAOYSA-N 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229910000039 hydrogen halide Inorganic materials 0.000 claims 1
- 239000012433 hydrogen halide Substances 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 239000002249 anxiolytic agent Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- -1 hydrogen halides Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000005995 Aluminium silicate Substances 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 230000001741 anti-phlogistic effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- BUHYMJLFRZAFBF-UHFFFAOYSA-N 3,4,5-trimethoxybenzoyl chloride Chemical compound COC1=CC(C(Cl)=O)=CC(OC)=C1OC BUHYMJLFRZAFBF-UHFFFAOYSA-N 0.000 description 1
- SBAJRGRUGUQKAF-UHFFFAOYSA-N 3-(2-cyanoethylamino)propanenitrile Chemical compound N#CCCNCCC#N SBAJRGRUGUQKAF-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 102000005327 Palmitoyl protein thioesterase Human genes 0.000 description 1
- 108020002591 Palmitoyl protein thioesterase Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012213 gelatinous substance Substances 0.000 description 1
- 229940083761 high-ceiling diuretics pyrazolone derivative Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
- C07D231/46—Oxygen atom in position 3 or 5 and nitrogen atom in position 4
- C07D231/50—Acylated on said nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von 4-(3,4,5-Trimethoxybenzoylamido)-l-pheßy 2,3-dimethylpyrazolon-(5) Die Erfindung befaßt sich mit einem Verfahren zur Herstellung von 4-(3,4,5 -Trimethoxybenzoylamido)-1-phenyl-2,3-dimethyl-pyrazolon-(5) der allgemeinen Formel bei dem man in an sich bekannter Weise 3,4,5-Trimethoxybenzoesäure oder ihre funktionellen Derivate, wie das Chlorid oder deren Ester, mit l-Phenyl-2,3-dimethyl-4-amino-pyrazolon-(5) umsetzt. Bei der Verwendung von 3,4,5-Trimethoxybenzoesäure werden dem Reaktionsgemisch gegebenenfalls wasserabspaltende Mittel, wie Phosphoroxychlorid, zugesetzt. Auch die Gegenwart halogenwasserstoffbindender Mittel, wie Trimethylamin oder Pyridin, ist gegebenenfalls zweckvoll.Process for the preparation of 4- (3,4,5-trimethoxybenzoylamido) -l-pheßy 2,3-dimethylpyrazolone- (5) The invention relates to a process for the preparation of 4- (3,4,5 -trimethoxybenzoylamido) - 1-phenyl-2,3-dimethyl-pyrazolone- (5) of the general formula in which, in a manner known per se, 3,4,5-trimethoxybenzoic acid or its functional derivatives, such as the chloride or its ester, are reacted with l-phenyl-2,3-dimethyl-4-aminopyrazolone- (5). If 3,4,5-trimethoxybenzoic acid is used, dehydrating agents, such as phosphorus oxychloride, may be added to the reaction mixture. The presence of agents that bind hydrogen halides, such as trimethylamine or pyridine, may also be expedient.
Die Umsetzung kann sowohl in Gegenwart oder Abwesenheit von Lösungsmitteln ausgeführt werden. The reaction can be carried out either in the presence or absence of solvents are executed.
Als Lösungs- und Verdünnungsmittel eignen sich vorzüglich Benzol kohlenwasserstoffe, wie Toluol oder Xylole.Benzene hydrocarbons are particularly suitable as solvents and diluents, such as toluene or xylenes.
Die neue analgetisch wirksame Verbindung soll als Heilmittel Verwendung finden. The new analgesic compound is said to be used as a remedy Find.
Es wurde gefunden, daß die Toxizität des Verfahrensproduktes außerordentlich gering ist. So beträgt die an der Maus gemessene DL50 intraperitoneal (ausgewertet nach K ä r b e r) 2,5 glkg. It has been found that the toxicity of the process product is extraordinary is low. The DL50 measured on the mouse is thus intraperitoneally (evaluated according to Kärber) 2.5 glkg.
Auch bei chronischer Zuführung des 4-(3,4,5-Trimethoxybenzoylamido)-1-phenyl-2,3-dimethylpyrazolon-(5) in Mengen von 80mglkg oral über 4 Monate hindurch traten keine krankhaften Veränderungen der inneren Organe oder Gewichtsveränderungen ein. Die Überlegenheit des Verfahrensproduktes soll an Hand von pharmakologischen Vergleichsversuchen mit dem Verfahrensprodukt gegenüber bekannten Verbindungen der gleichen Wirkungsrichtung nachgewiesen werden. Even with chronic intake of 4- (3,4,5-trimethoxybenzoylamido) -1-phenyl-2,3-dimethylpyrazolone- (5) in amounts of 80 mg / kg orally over 4 months there were no pathological changes internal organs or changes in weight. The superiority of the process product should on the basis of pharmacological comparative tests with the process product compared to known compounds of the same direction of action can be demonstrated.
Aus der nachfolgenden Tabelle ergibt sich die Uberlegenheit der nach dem erfindungsgemäßen Verfahren hergestellten Verbindung des 4-(3,4,5-Trimethoxybenzoylamido)-1-phenyl-2,3- -dimethyl-pyrazolons-(5) (Verbindung I) im Vergleich zu bekannten Amiden, wie dem 4-Salicylamido-l-phenyl-2.3-dimethyl-pyrazolon-(5) (Verbindung II), dem Nicotin- säureamido-1-phenyl-2,3-dimethyl-pyrazolon- (5) (Verbindung III) und dem 4Dimetbylamino- 1 -phenyl-2,3-dimethyl-pyrazolon-(5) (Verbindung IV). The table below shows the superiority of the after the process according to the invention prepared compound of 4- (3,4,5-trimethoxybenzoylamido) -1-phenyl-2,3- -dimethyl-pyrazolons- (5) (compound I) compared to known amides, such as the 4-salicylamido-l-phenyl-2,3-dimethyl-pyrazolone- (5) (compound II), the nicotine acid amido-1-phenyl-2,3-dimethyl-pyrazolone- (5) (Compound III) and the 4-dimetbylamino-1-phenyl-2,3-dimethyl-pyrazolone- (5) (Compound IV).
Die Das wurde oral und intraperitoneal an Mäusen bestimmt. Die Substanzen wurden in einer 25%igen Gummiarabikumemulsion fein verteilt emulgiert. Die Bestimmung der DL5o erfolgte nach Kärber. The Das was determined orally and intraperitoneally in mice. The substances were finely dispersed emulsified in a 25% gum arabic emulsion. The determination the DL5o took place in Kärber.
Die analgetische Wirkung wurde nach intraperitonealer Einverleibung an der Maus nach der »hotplate«-Methode bestimmt. ED50 bezeichnet diejenige Dosis, nach der die Schmerzlatenzzeit bei 5010 der Tiere um mehr als die Hälfte verlängert ist. The analgesic effect was observed after intraperitoneal incorporation determined on the mouse using the "hotplate" method. ED50 denotes the dose after which the pain latency period was extended by more than half in 5010 animals is.
Versuchszeit 180 Minuten.Experiment time 180 minutes.
Die antipyretische Wirkung wurde am Hefefieber der Ratte bestimmt. Es erhielten je zehn Ratten 16 Stunden vor Versuchsbeginn 1 ml einer 20%igen Bierhefesuspension subkutan. Die erhaltenen Zahlen zeigen die Mittelwerte und geben die maximale Temperatursenkung während einer Meßperiode von 3 Stunden bei Messung in 30 Minuten Abständen an. The antipyretic effect was determined on the yeast fever of the rat. Each ten rats received 1 ml of a 20% brewer's yeast suspension 16 hours before the start of the experiment subcutaneous. The numbers obtained show the mean values and give the maximum temperature decrease during a measuring period of 3 hours when measuring at 30 minute intervals.
Es wurde als einheitliche Dosis 30 mglkg Substanz intraperitoneal verabreicht.It was given intraperitoneally as a uniform dose of 30 mglkg of substance administered.
Die tranquillosedativen Eigenschaften wurden durch Bestimmung der mittleren Wirkungsmenge für die Motilität (= Bewegungsaktivität) in der Weise ermittelt, daß bei den Tieren (Mäusen) vorher mit Iminodipropionsäurenitril eine irreveriable Erhöhung der motorischen Aktivität erzeugt wird, die bekanntlich durch Tranquillosedativa aufgehoben werden kann. Die TD50-Dosis gibt nun jene Menge bzw. Dosis an, bei der 50% der Tiere im Versuch den erwarteten Effekt zeigten. The tranquillosedative properties were determined by determining the mean amount of action for motility (= movement activity) determined in such a way that that in the animals (mice) previously with iminodipropiononitrile an irreverable Increase in motor activity is produced, which is known to be caused by Tranquillose edativa can be canceled. The TD50 dose now gives that amount respectively. Dose at which 50% of the animals in the experiment showed the expected effect.
Die antiphlogistische Wirkung wurde am Rattenpt'oten-Kaolinödem bei
oraler Zuführung [Arzneimittel-Forschung, Bd. 4, S. 607 (1954); Bd. 10, S. 843 (1960)]
bestimmt. Die AD40-Dosis gibt jene Dosis an. bei welcher eine 50%ige Hemmung der
Kaolinödeme erzielt wurde.
Wird jedoch der Wirkungseffekt, also der Quotient, aus DLso und den einzelnen Wirkungsarten, wie ED50 für Analgesie, AD50 für die antiphologistische Wirkung gebildet, so schneidet in allen Fällen die nach dem erfindungsgemäßen Verfahren erhaltene Verbindung 1 günstiger ab. Die bekannten Verbindungen II und III sind in allen Fällen schwächer wirksam. Weder Verbindung IV noch die Verbindungen II und III besitzen eine tranquillosedative Wirkung, die gerade bei Schmerzstillungsmitteln von größter praktischer Bedeutung ist. Im Gegenteil, Verbindung IV und auch zahlreiche andere Pyrazolonderivate besitzen die unangenehme Eigenschaft, in hohen Dosen zentralnervöse Störungen zu verursachen.However, if the effect, i.e. the quotient, is made up of DLso and the individual types of action, such as ED50 for analgesia, AD50 for antiphologistic If the effect is formed, that cuts in all cases according to the method according to the invention Compound 1 obtained cheaper. The known compounds II and III are in all cases less effective. Neither compound IV nor the compounds II and III have a tranquillosedative effect, especially with painkillers is of the greatest practical importance. On the contrary, compound IV and also numerous other pyrazolone derivatives have the unpleasant property of being central nervous in high doses To cause interference.
Wenn es auch bereits eine Reihe von Verbindungen mit tranquillosedativer Wirkung, wie 3,4,5-Trimethoxybenzoyl-morpholinoamide, gibt, so besitzen diese keinerlei analgetische oder antiphologistische Wirkung. Diese nach dem erfindungsgemäßen Verfahren hergestellte Verbindung hat also gegenüber bekannten Verbindungen ähnlicher Konstitution erhebliche Vorteile. Even if there are already a number of connections with tranquillosedative Effect, such as 3,4,5-trimethoxybenzoyl-morpholinoamide, gives, so they have no analgesic or antiphologistic effect. This according to the method according to the invention The connection established thus has a constitution similar to that of known compounds significant benefits.
Beispiel 1 23 g 3,4,5-Trimethoxybenzoesäurechlorid werden in eine Lösung von 40 g I-Phenyl-2,3-dimethyl-4-amino-pyrazolon-(5) in 150 ml wasserfreiem Benzol portionsweise unter Kühlung so. daß die Temperatur nicht 40°C übersteigt, eingetragen. Es entwickelt sich ein dicker, harziger Niederschlag. Nach Beendigung der Zugabe wird das Reaktionsgut noch 1 Stunde unter Rückfluß auf dem Wasserbad erwärmt, sodann läßt man abkühlen, dekantiert das Benzol ab und versetzt den gelbrotgefärbten Niederschlag mit 300 ml Wasser. Es wird 30 Minuten unter Rühren auf 60 bis 80°C erhitzt, sodann wird abkühlen gelassen und mit 20%iger Sodalösung neutralisiert, wobei der Niederschlag kristallin wird. Example 1 23 g of 3,4,5-trimethoxybenzoic acid chloride are in a Solution of 40 g of I-phenyl-2,3-dimethyl-4-aminopyrazolone- (5) in 150 ml of anhydrous Benzene in portions with cooling like that. that the temperature does not exceed 40 ° C, registered. A thick, resinous precipitate develops. After completion After the addition, the reaction mixture is refluxed for 1 hour on the water bath heated, then allowed to cool, decanted off the benzene and added the yellow-red colored Precipitate with 300 ml of water. It is heated to 60 to 80 ° C. for 30 minutes while stirring heated, then allowed to cool and neutralized with 20% soda solution, whereby the precipitate becomes crystalline.
Man saugt ab und wäscht mit Wasser aus (aus der Mutterlauge läßt sich 1-Phenyl-2,3-dimethyl-4-aminopyrazolon-(5) durch starkes Alkalisieren und Extraktion mit Benzol zurückgewinnen). Der nun braungelbe kristalline Filterrückstand wird aus Alkohol umkristallisiert. Man erhält das 4-(3,4,5-Trimethoxybenzoylamido) - 1 -phenyi-2,3 -dimethyl-pyrazolon -(5) in Form von schwach gelbgefärbten Nadeln. It is suctioned off and washed with water (leaves from the mother liquor 1-phenyl-2,3-dimethyl-4-aminopyrazolon- (5) by strong alkalization and extraction recover with benzene). The now brown-yellow crystalline filter residue is from alcohol recrystallized. The 4- (3,4,5-trimethoxybenzoylamido) -1 is obtained -phenyi-2,3-dimethyl-pyrazolon - (5) in the form of pale yellow needles.
F. 212 bis 214°C, Ausbeute: 22 g. M.p. 212-214 ° C, yield: 22 g.
Beispiel 2 42 g 3,4,5-Trimethoxybenzoesäure und 40 g l-Phehyl-2,3-dimethyl-4-amino-pyrazolon-(5) werden in 100 ml Toluol suspendiert. Dazu gibt man 32 ml Triäthylamin, wobei sich die Suspension vollständig löst. Nun läßt man unter Rühren tropfenweise 25 ml Phosphoroxychlorid zufließen und reguliert den Zufluß von Phosphoroxychlorid dergestalt, daß die Temperatur nicht 80°C übersteigt. Am Anfang der Zugabe muß das Reaktionsgefäß mit kaltem Wasser gekühlt werden. Es tritt Abscheidung einergelatinösen Substanz ein. Nach Beendigung der Zugabe von Phosphoroxychlorid wird noch 2 bis 3 Stunden unter Rückfluß gekocht, wobei der Niederschlag in ein braungelbes Harz übergeht. Man läßt erkalten, dekantiert von dem Toluol ab und nimmt den öligen Rückstand mit 200 ml Wasser auf, kocht auf und bringt mit 200/oiger Sodalösung auf pH 8. Das sich abscheidende U1 erstarrt kristallin und kann nach 2 bis 3 Stunden Stehen gut filtriert werden. Ausbeute 60 g. Das erhaltene 4-(3,4,5-Trimethoxybenzoylami do)-1-phenyl-2,3- dimethyl - pyrazolon - (5) wird aus heißem Alkohol umkristallisiert. F. 212 bis 214°C, Durch Ansäuern der alkalischen Lösung fallen noch 6 g nicht umgesetzte 3,4,5-Trimethoxybenzoesäure aus. Example 2 42 g of 3,4,5-trimethoxybenzoic acid and 40 g of l-phenyl-2,3-dimethyl-4-aminopyrazolone- (5) are suspended in 100 ml of toluene. To this one gives 32 ml of triethylamine, whereby the suspension dissolves completely. 25 ml of phosphorus oxychloride are now left in dropwise with stirring flow in and regulates the flow of phosphorus oxychloride so that the temperature does not exceed 80 ° C. At the beginning of the addition, the reaction vessel must be filled with cold water be cooled. Deposition of a gelatinous substance occurs. After completion the addition of phosphorus oxychloride is refluxed for 2 to 3 hours, the precipitate turns into a brownish-yellow resin. Allow to cool, decanted from the toluene and takes up the oily residue with 200 ml of water, boils up and brings it to pH 8 with 200% soda solution. The U1 which separates out solidifies crystalline and can be filtered well after standing for 2 to 3 hours. Yield 60 G. The 4- (3,4,5-trimethoxybenzoylamido) -1-phenyl-2,3-dimethyl-pyrazolone obtained - (5) is recrystallized from hot alcohol. M.p. 212 to 214 ° C, by acidification 6 g of unreacted 3,4,5-trimethoxybenzoic acid still fall from the alkaline solution the end.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK44970A DE1200309B (en) | 1961-10-19 | 1961-10-19 | Process for the preparation of 4- (3, 4,5-trimethoxybenzoylamido) -1-phenyl-2, 3-dimethylpyrazolone- (5) |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK44970A DE1200309B (en) | 1961-10-19 | 1961-10-19 | Process for the preparation of 4- (3, 4,5-trimethoxybenzoylamido) -1-phenyl-2, 3-dimethylpyrazolone- (5) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1200309B true DE1200309B (en) | 1965-09-09 |
Family
ID=7223668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEK44970A Pending DE1200309B (en) | 1961-10-19 | 1961-10-19 | Process for the preparation of 4- (3, 4,5-trimethoxybenzoylamido) -1-phenyl-2, 3-dimethylpyrazolone- (5) |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1200309B (en) |
-
1961
- 1961-10-19 DE DEK44970A patent/DE1200309B/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| None * |
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