DE1150087B - Process for the preparation of 4,8-Dimorpholino-pyrimido- [5, 4-d] pyrimidines - Google Patents
Process for the preparation of 4,8-Dimorpholino-pyrimido- [5, 4-d] pyrimidinesInfo
- Publication number
- DE1150087B DE1150087B DET23147A DET0023147A DE1150087B DE 1150087 B DE1150087 B DE 1150087B DE T23147 A DET23147 A DE T23147A DE T0023147 A DET0023147 A DE T0023147A DE 1150087 B DE1150087 B DE 1150087B
- Authority
- DE
- Germany
- Prior art keywords
- pyrimido
- dimorpholino
- ethoxy
- pyrimidines
- pyrimidine
- 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
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Verfahren zur Herstellung von 4, 8-Dimorpholino-pyrimido-[5 ,4-d]pyrimidinen Die Erfindung betrifft ein Verfahren zur Herstellung von 4,8-Dimorpholino-pyrimido [5,4-d]pyrimidinen der allgemeinen Formel worin R einen ß-Äthoxy-äthoxy- oder ß-Propoxyäthoxyrest bedeutet.Process for the preparation of 4,8-dimorpholino-pyrimido- [5, 4-d] pyrimidines The invention relates to a process for the preparation of 4,8-dimorpholino-pyrimido [5,4-d] pyrimidines of the general formula wherein R is a ß-ethoxy-ethoxy or ß-propoxyethoxy radical.
Die Herstellung der neuen Pyrimido[5,4-d]pyrimidine erfolgt dadurch, daß man in an sich bekannter Weise 2-Chlor - 4,8- dimorpholino - pyrimido [5,4-d]-pyrimidin bei erhöhter Temperatur in Anwesenheit eines säurebindenden Mittels mit einer Verbindung der allgemeinen Formel HR umsetzt oder mit einer Verbindung der allgemeinen Formel MeR, worin Me ein Alkalimetallatom darstellt, zur Reaktion bringt. The new pyrimido [5,4-d] pyrimidines are produced by that in a manner known per se, 2-chloro-4,8-dimorpholino-pyrimido [5,4-d] -pyrimidine at elevated temperature in the presence of an acid-binding agent with a compound of the general formula HR or with a compound of the general formula MeR, in which Me represents an alkali metal atom, reacts.
Säurebindende Mittel, die bei dem erfindung gemäßen Verfahren angewendet werden, sind z. B. Acid-binding agents used in the method according to the invention are z. B.
Alkalihydroxyde, Alkalicarbonate od er tertiäre Amine 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 erfolgen. Auch das als zweite Reaktionskomponente eingesetzte Glykolderivat kann gegebenenfalls im Überschuß als Lösungs- und Verdünnungsmittel Verwendung finden.Alkali hydroxides, alkali carbonates or tertiary amines The process can in the presence or absence of solvents or diluents which are inert for the reaction, z. B. acetone, dioxane, benzene, xylene or dimethylformamide and optionally under Apply pressure. Also that used as the second reaction component Glycol derivative can optionally be used in excess as a solvent and diluent Find use.
Das als Ausgangsverbindung verwendete 2-Chlor-4,8 - dimorpholino - pyrimido[5,4 - d]pyrimidin wird aus 2,4,8 -Trichlor-pyrimido[5,4 - d]pyrimidin durch Umsetzung mit Morpholin hergestellt. Das 2,4,8-Trichlor - pyrimido[5,4 - d]pyrimidin wird vorteilhaft durch Erhitzen von 2,4,8-Trioxy-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-chloro-4,8 - dimorpholino used as the starting compound - Pyrimido [5,4 - d] pyrimidine is made from 2,4,8 - trichloropyrimido [5,4 - d] pyrimidine produced by reaction with morpholine. The 2,4,8-trichloro-pyrimido [5,4-d] pyrimidine is advantageously obtained by heating 2,4,8-trioxy-pyrimido [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.
Die nach dem erfindungsgemäßen Verfahren hergestellten Pyrimido [5,4-d]pyrimidine sind wertvolle Arzneimittel, die insbesondere herz- und kreislaufwirksam sind. Sie sind hinsichtlich ihrer coronarerweiternden Wirkung dem Theophyllin, wie im folgenden gezeigt wird, überlegen. The pyrimido [5,4-d] pyrimidines prepared by the process according to the invention are valuable drugs that are particularly beneficial for the heart and circulatory system. she are theophylline in terms of their 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.
Die folgenden Beispiele sollen die Erfindung näher erläutern: Beispiel 1 2-(,B-Äthoxy-äthoxy)-4,8-dimorpholinopyrimido [5,4-d]pyrimidin 6,7 g (0,02 Mol) 2-Chlor-4,8-dimorpholino-pyrimido[5,4-d]pyrimidin wurden mit einer Lösung von 0,5 g (0,022 Mol) Natrium in 100 cm Äthylglykol 1 Stunde unter Rückfluß gekocht. Beim Eingießen der Reaktionslösung in 400 ccm Wasser fiel das rohe 2 - (ß - Äthoxy - äthoxy) 4,8 - dimorpholino - pyrimido[5,4-d]pyrimidin als farbloser Niederschlag aus. The following examples are intended to explain the invention in more detail: Example 1 2 - (, B-ethoxy-ethoxy) -4,8-dimorpholinopyrimido [5,4-d] pyrimidine 6.7 g (0.02 mol) 2-Chloro-4,8-dimorpholino-pyrimido [5,4-d] pyrimidine were treated with a solution of 0.5 g (0.022 mol) of sodium in 100 cm of ethyl glycol refluxed for 1 hour. At the Pouring the reaction solution into 400 ccm of water fell the crude 2 - (ß - ethoxy - ethoxy) 4,8 - dimorpholino - pyrimido [5,4-d] pyrimidine as a colorless precipitate the end.
Es wurde zur Reinigung einmal aus etwa 1 n-Salzsäure umgefällt: sehr feine, farblose Nädelchen F. 111 bis 112"C; Ausbeute 6,0 g (770/0 der Theorie).It was reprecipitated once from about 1N hydrochloric acid for purification: very fine, colorless needles F. 111 to 112 "C; yield 6.0 g (770/0 of theory).
Beispiel 2 2-(8-Propoxy-äthoxy)-4,8-dimorpholinopyrimido [5,4-d]pyrimidin Darstellung analog der im Beispiel 1 beschriebenen Umsetzung; F. 124 bis 126"C. Example 2 2- (8-propoxy-ethoxy) -4,8-dimorpholinopyrimido [5,4-d] pyrimidine Representation analogous to the implementation described in Example 1; F. 124 to 126 "C.
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DET23147A DE1150087B (en) | 1956-04-25 | 1956-04-25 | Process for the preparation of 4,8-Dimorpholino-pyrimido- [5, 4-d] pyrimidines |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DET23147A DE1150087B (en) | 1956-04-25 | 1956-04-25 | Process for the preparation of 4,8-Dimorpholino-pyrimido- [5, 4-d] pyrimidines |
Publications (1)
Publication Number | Publication Date |
---|---|
DE1150087B true DE1150087B (en) | 1963-06-12 |
Family
ID=7550871
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DET23147A Pending DE1150087B (en) | 1956-04-25 | 1956-04-25 | Process for the preparation of 4,8-Dimorpholino-pyrimido- [5, 4-d] pyrimidines |
Country Status (1)
Country | Link |
---|---|
DE (1) | DE1150087B (en) |
-
1956
- 1956-04-25 DE DET23147A patent/DE1150087B/en active Pending
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