DE1150084B - Process for the preparation of 2, 4, 6, 8-tetra- (allylamino) -pyrimido- [5, 4-d] pyrimidine - Google Patents

Process for the preparation of 2, 4, 6, 8-tetra- (allylamino) -pyrimido- [5, 4-d] pyrimidine

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Publication number
DE1150084B
DE1150084B DET23144A DET0023144A DE1150084B DE 1150084 B DE1150084 B DE 1150084B DE T23144 A DET23144 A DE T23144A DE T0023144 A DET0023144 A DE T0023144A DE 1150084 B DE1150084 B DE 1150084B
Authority
DE
Germany
Prior art keywords
pyrimidine
pyrimido
tetra
allylamino
preparation
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
Application number
DET23144A
Other languages
German (de)
Inventor
Dr Franz Gottwalt Fischer
Dr Josef Roch
Dr August Kottler
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim Pharma GmbH and Co KG
Original Assignee
Dr Karl Thomae GmbH
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Dr Karl Thomae GmbH filed Critical Dr Karl Thomae GmbH
Priority to DET23144A priority Critical patent/DE1150084B/en
Publication of DE1150084B publication Critical patent/DE1150084B/en
Pending legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

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  • 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 2,4,6,8-Tetra-(allylamino)-pyrimido-[5,4-d]pyrimidin Die Erfindung betrifft ein Verfahren zur Herstellung von 2,4,6,8 - Tetra - (allylamino) - pyrimido[5,4-d]pyrimidin durch in an sich bekannter Weise durchgeführte Umsetzung von 2,4,6,8-Tetrachlor-pyrimido [5,4d]-pyrimidin mit Allylamin bei einer Temperatur zwischen 150 und 250"C in Anwesenheit eines säurebindenden Mittels. Process for the preparation of 2,4,6,8-tetra- (allylamino) -pyrimido- [5,4-d] pyrimidine The invention relates to a process for the preparation of 2,4,6,8 - tetra - (allylamino) - pyrimido [5,4-d] pyrimidine by reaction carried out in a manner known per se of 2,4,6,8-tetrachloropyrimido [5,4d] pyrimidine with allylamine at one temperature between 150 and 250 "C in the presence of an acid-binding agent.

Säurebindende Mittel, die bei dem Verfahren angewendet werden, sind z. B. Alkalihydroxyde, Alkalicarbonate oder tertiäre Amine; gegebenenfalls kann auch mit einem Überschuß an Allylamin gearbeitet werden. Acid binding agents used in the process are z. B. alkali hydroxides, alkali carbonates or tertiary amines; possibly can can also be used with an excess of allylamine.

Das Verfahren kann in An- oder Abwesenheit von für die Reaktion inerten Lösungs- bzw. Verdünnungsmitteln, z. B. Aceton, Dioxan, Benzol, Xylol oder Dimethylformamid und gegebenenfalls unter Anwendung von Druck durchgeführt werden. Es ist auch möglich, Allylamin im Überschuß als Lösungs- oder Verdünnungsmittel anzuwenden. Bei der erfindungsgemäßen Reaktion ist es auch vorteilhaft, als Reaktionsbeschleuniger ein Kupfersalz, beispielsweise Kupfersulfat, zuzusetzen. The process can be inert to the reaction in the presence or absence Solvents or diluents, e.g. B. acetone, dioxane, benzene, xylene or dimethylformamide and optionally carried out with the application of pressure. It is also possible, Allylamine to be used in excess as a solvent or diluent. In the inventive Reaction, it is also advantageous as a reaction accelerator a copper salt, for example Copper sulfate, to be added.

Das als Ausgangsmaterial benutzte 2,4,6,8-Tetrachlor-pyrimido[5,4-d]pyrimidin wird vorteilhaft durch Erhitzen von 2,4,6,8-Tetraoxy-pyrimido[5,4-d]pyrimidin (erhältlich gemäß dem Verfahren der deutschen Patentschrift 845 940) mit anorganischen Säurehalogeniden, vorzugsweise Phosphorhalogeniden, wie Phosphoroxychlorid oder Phosphorpentachlorid, hergestellt. The 2,4,6,8-tetrachloropyrimido [5,4-d] pyrimidine used as starting material is advantageously obtained by heating 2,4,6,8-tetraoxypyrimido [5,4-d] pyrimidine ( according to the method of German Patent 845 940) with inorganic acid halides, preferably phosphorus halides, such as phosphorus oxychloride or phosphorus pentachloride, manufactured.

Das nach dem erfindungsgemäßen Verfahren hergestellte 2,4,6,8 - Tetra - (allylamino) - pyrimido[5,4-d]-pyrimidin ist ein wertvolles Arzneimittel, das insbe- sondere herz- und kreislaufwirksam ist. Die Verbindung ist beispielsweise hinsichtlich ihrer coronarerweiternden Wirkung dem Theophyllin, wie im folgenden gezeigt wird, überlegen. The 2,4,6,8-Tetra produced by the process according to the invention - (Allylamino) - pyrimido [5,4-d] -pyrimidine is a valuable drug that especially is particularly effective for the heart and circulation. The connection is for example theophylline for its coronary-dilating effect, as follows is shown, consider.

Die Coronardurchblutung wurde am Hund mittels Rotameter nach der Methode von Eckenhoff und Mitarbeitern (Amer. Journ. Physiol., 148, S. 582 [1947]) gemessen. Die Applikation der zu prüfenden Substanz erfolgte intracoronar in schwach salzsaurer Lösung. Die Dosierung betrug 1 mg. Zunahme der Coronarwirkung Wirkungsdauer Substanz Coronar- (Theophyllin = 1) in Minuten durchblutung in /o Theophyllin . . . . . . 76 | 1 | 0,5 2,4,6,8-Tetra-(allylamino)-pyrimido [5,4-d]pyrimidin .. 120 1,5 >10 Wie die Gegenüberstellung zeigt, ist die erfindungsgemäß erhältliche Verbindung nicht nur stärker, sondern auch über zwanzigmal länger wirksam als Theophyllin.The coronary blood flow was measured in the dog by means of a rotameter according to the method of Eckenhoff and co-workers (Amer. Journ. Physiol., 148, p. 582 [1947]). The substance to be tested was applied intracoronarily in a weak hydrochloric acid solution. The dosage was 1 mg. Increase in the coronary effect duration of effect Substance coronary (theophylline = 1) in minutes blood circulation in / o Theophylline. . . . . . 76 | 1 | 0.5 2,4,6,8-Tetra (allylamino) pyrimido [5,4-d] pyrimidine .. 120 1.5> 10 As the comparison shows, the compound obtainable according to the invention is not only stronger but also more effective than theophylline for over twenty times longer.

Das folgende Beispiel soll die Erfindung näher erläutern. The following example is intended to explain the invention in more detail.

Beispiel 2,4,6,8-Tetra-(allylamino)-pyrimido [5,4-d]pyrimidin 5,4 g (0,02 Mol) 2,4,6,8-Tetrachlor-pyrimido[5,4-d]-pyrimidin wurden mit 30 ccm Allylamin und 0,1 g Kupfersulfat im Bombenrohr 1 Stunde lang auf 200"C erhitzt. Beim Versetzen des Reaktionsgemisches mit 200ccm Wasser schied sich das rohe 2,4,6,8-Tetra-(allylamino)-pyrimido[5,4-d]pyrimidin zunächst als zähe, schmierige Masse ab, die beim Stehen über Nacht erstarrte. Es wurde abgesaugt und getrocknet; Ausbeute: 5,8 g (82 01o der Theorie). Nach dreimaligem Umkristallisieren aus Dioxan wurde die Verbindung als hellgelbes, mikrokristallines, körniges Pulver erhalten; F. 201 bis 203°C. Example 2,4,6,8-Tetra (allylamino) pyrimido [5,4-d] pyrimidine 5.4 g (0.02 mol) of 2,4,6,8-tetrachloropyrimido [5,4-d] -pyrimidine were mixed with 30 cc of allylamine and 0.1 g Copper sulphate heated to 200 ° C for 1 hour in a bomb tube. When moving the reaction mixture with 200ccm water separated the crude 2,4,6,8-tetra- (allylamino) -pyrimido [5,4-d] pyrimidine initially as a tough, greasy mass that solidified when standing overnight. It was sucked off and dried; Yield: 5.8 g (82,010 of theory). After three times Recrystallization from dioxane gave the compound as a light yellow, microcrystalline, get granular powder; M.p. 201 to 203 ° C.

Claims (2)

PATENTANSPRÜCHE 1. Verfahren zur Herstellung von 2,4,6,8-Tetra-(aliylamino)-pyrimido [5,4-d]pyrimidin, dadurch ge kennzeichnet, daß man in an sich bekannter Weise 2,4,6,8 -Tetrachlor- pyrimido 5,4- dipyrimidin bei einer Temperatur zwischen 150 und 250"C in Anwesenheit eines säurebindenden Mittels mit Allylamin umsetzt. PATENT CLAIMS 1. Process for the preparation of 2,4,6,8-tetra- (aliylamino) -pyrimido [5,4-d] pyrimidine, characterized in that 2,4,6,8 -Tetrachloropyrimido 5,4-dipyrimidine a temperature between 150 and 250 "C reacts with allylamine in the presence of an acid-binding agent. 2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß als Reaktionsbeschleuniger ein Kupfersalz zugesetzt wird. 2. The method according to claim 1, characterized in that as a reaction accelerator a copper salt is added.
DET23144A 1956-04-25 1956-04-25 Process for the preparation of 2, 4, 6, 8-tetra- (allylamino) -pyrimido- [5, 4-d] pyrimidine Pending DE1150084B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DET23144A DE1150084B (en) 1956-04-25 1956-04-25 Process for the preparation of 2, 4, 6, 8-tetra- (allylamino) -pyrimido- [5, 4-d] pyrimidine

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DET23144A DE1150084B (en) 1956-04-25 1956-04-25 Process for the preparation of 2, 4, 6, 8-tetra- (allylamino) -pyrimido- [5, 4-d] pyrimidine

Publications (1)

Publication Number Publication Date
DE1150084B true DE1150084B (en) 1963-06-12

Family

ID=7550867

Family Applications (1)

Application Number Title Priority Date Filing Date
DET23144A Pending DE1150084B (en) 1956-04-25 1956-04-25 Process for the preparation of 2, 4, 6, 8-tetra- (allylamino) -pyrimido- [5, 4-d] pyrimidine

Country Status (1)

Country Link
DE (1) DE1150084B (en)

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