CH361283A - Process for the preparation of new pyrimidines - Google Patents

Process for the preparation of new pyrimidines

Info

Publication number
CH361283A
CH361283A CH361283DA CH361283A CH 361283 A CH361283 A CH 361283A CH 361283D A CH361283D A CH 361283DA CH 361283 A CH361283 A CH 361283A
Authority
CH
Switzerland
Prior art keywords
sep
preparation
formula
new pyrimidines
malonic acid
Prior art date
Application number
Other languages
German (de)
Inventor
Habicht Ernst Dr Phil
Original Assignee
Cilag Chemie Aktiengesellschaf
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 Cilag Chemie Aktiengesellschaf filed Critical Cilag Chemie Aktiengesellschaf
Publication of CH361283A publication Critical patent/CH361283A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

  

  
 



  Verfahren zur Herstellung von neuen Pyrimidinen
Die vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung neuer Pyrimidine der Formel
EMI1.1     
 in welcher   Rt    eine durch einen oder zwei aliphatische Reste substituierte Aminogruppe, R2 Alkyl und R3 Wasserstoff oder niederes Alkyl bedeutet.



  Solche   Pyrimidinderivate    besitzen wertvolle pharmakologische Eigenschaften. Sie wirken insbesondere diuretisch und coronardilatierend.



   Die neuen Pyrimidine der Formel I werden erfindungsgemäss hergestellt durch Umsetzen eines substituierten Guanidins der Formel
EMI1.2     
 mit einem Dialkylester einer Alkoxymethylenmalonsäure oder einer a-Alkoxy-alkylidenmalonsäure. Die Umsetzung erfolgt vorzugsweise in einem Lösungsmittel bzw. Verdünnungsmittel, wie z. B. in einem niederen Alkanol.



   Die Kondensation wird vorzugsweise in alkalischem Milieu, das heisst in Gegenwart alkalisch wirkender Substanzen, wie z. B. Natriummethanolat, Natriumäthanolat oder anderer hierfür geeigneter Agenzien, vorgenommen. Hierbei kann das substituierte Guanidin der Formel II auch in Salzform eingesetzt werden, wobei dann entsprechende Mengen Alkali zur Freisetzung des Guanidins-verwendet werden.



   Beispiel
84 g n-Propylguanidinsulfat werden mit 145 g   Äthoxymethylenmalonsäurediäthylester    in 250   cm5    abs.   Äthanol,    der 13 g Natrium gelöst enthält, unter Rühren 2 Stunden zum Sieden erhitzt. Anschliessend destilliert man das Lösungsmittel ab, versetzt mit Wasser und Essigsäure und saugt das gebildete 2-(n  Propylamino)-4-hydroxy-5-carbäthoxy-pyrimidin    ab.



  Nach dem Umkristallisieren aus Essigsäureäthylester/ Chloroform erhält man 70 g des bei   212-212,5"C    schmelzenden reinen Esters.



   Die folgenden   2-R1-4Hydroxy-pyrimidin-5 -car-    bonsäureäthylester können in gleicher Weise, wie im Beispiel beschrieben, hergestellt werden:
EMI1.3     


<tb>  <SEP> R1 <SEP> R1 <SEP> Schmelzpunkt <SEP> | <SEP> Rz <SEP> |
<tb>  <SEP> oC <SEP> oC
<tb>  <SEP> /CH5
<tb> -NH-CH5 <SEP> 242 <SEP> -N <SEP> 165-167
<tb>  <SEP> CH3
<tb> -NH-C5H7 <SEP> iso <SEP> 193-195 <SEP> -NHC3H5 <SEP> 218-219
<tb>   
EMI2.1     


<tb>  <SEP> R1 <SEP> Schmelzpunkt <SEP> | <SEP> R1 <SEP> | <SEP> Schmelzpunkt
<tb>  <SEP> oC <SEP> oC
<tb>  <SEP> CH3
<tb> -N <SEP> 137-138 <SEP> -NH-C4H9 <SEP> n <SEP> 205-206
<tb>  <SEP> C2H5
<tb> -NH-C4H9 <SEP> iso <SEP> 208-209 <SEP> -NH-C4H9 <SEP> sec.

   <SEP> 163-165
<tb>  <SEP> yC2Hs
<tb> -N <SEP> 92-93 <SEP> -NH-C5H11 <SEP> n <SEP> 180-182
<tb>  <SEP> C2H5
<tb> -NH-C5H11 <SEP> iso <SEP> 210-211 <SEP> -NH-C6H13 <SEP> n <SEP> 176-177
<tb> -NH-C2H4S-CH3 <SEP> 220-221 <SEP> -NHC2H4OCH5 <SEP> 200-202
<tb>  <SEP> .CH3
<tb> -NH-C5H6OCH3 <SEP> 178-180 <SEP> -NH-C3H6O <SEP> CH <SEP> 155-157
<tb>  <SEP> yC2H5 <SEP> CH3
<tb> -NH-C2H4N <SEP> 156-158 <SEP> -NH-C2H5 <SEP> 205-206
<tb>  <SEP> C2H5
<tb>    



  
 



  Process for the preparation of new pyrimidines
The present invention relates to a process for the preparation of new pyrimidines of the formula
EMI1.1
 in which Rt is an amino group substituted by one or two aliphatic radicals, R2 is alkyl and R3 is hydrogen or lower alkyl.



  Such pyrimidine derivatives have valuable pharmacological properties. In particular, they have a diuretic and coronary dilating effect.



   The new pyrimidines of the formula I are prepared according to the invention by reacting a substituted guanidine of the formula
EMI1.2
 with a dialkyl ester of an alkoxymethylene malonic acid or an α-alkoxy-alkylidene malonic acid. The reaction is preferably carried out in a solvent or diluent, such as. B. in a lower alkanol.



   The condensation is preferably carried out in an alkaline medium, that is, in the presence of alkaline substances, such as. B. sodium methoxide, sodium ethanolate or other suitable agents are made. The substituted guanidine of the formula II can also be used in salt form, in which case appropriate amounts of alkali are used to release the guanidine.



   example
84 g of n-propylguanidine sulfate are combined with 145 g of ethoxymethylene malonic acid diethyl ester in 250 cm5 abs. Ethanol containing 13 g of dissolved sodium, heated to boiling for 2 hours with stirring. The solvent is then distilled off, water and acetic acid are added and the 2- (n propylamino) -4-hydroxy-5-carbethoxypyrimidine formed is filtered off with suction.



  After recrystallization from ethyl acetate / chloroform, 70 g of the pure ester melting at 212-212.5 ° C. are obtained.



   The following 2-R1-4-hydroxy-pyrimidine-5-carboxylic acid ethyl ester can be prepared in the same way as described in the example:
EMI1.3


<tb> <SEP> R1 <SEP> R1 <SEP> melting point <SEP> | <SEP> Rz <SEP> |
<tb> <SEP> oC <SEP> oC
<tb> <SEP> / CH5
<tb> -NH-CH5 <SEP> 242 <SEP> -N <SEP> 165-167
<tb> <SEP> CH3
<tb> -NH-C5H7 <SEP> iso <SEP> 193-195 <SEP> -NHC3H5 <SEP> 218-219
<tb>
EMI2.1


<tb> <SEP> R1 <SEP> melting point <SEP> | <SEP> R1 <SEP> | <SEP> melting point
<tb> <SEP> oC <SEP> oC
<tb> <SEP> CH3
<tb> -N <SEP> 137-138 <SEP> -NH-C4H9 <SEP> n <SEP> 205-206
<tb> <SEP> C2H5
<tb> -NH-C4H9 <SEP> iso <SEP> 208-209 <SEP> -NH-C4H9 <SEP> sec.

   <SEP> 163-165
<tb> <SEP> yC2Hs
<tb> -N <SEP> 92-93 <SEP> -NH-C5H11 <SEP> n <SEP> 180-182
<tb> <SEP> C2H5
<tb> -NH-C5H11 <SEP> iso <SEP> 210-211 <SEP> -NH-C6H13 <SEP> n <SEP> 176-177
<tb> -NH-C2H4S-CH3 <SEP> 220-221 <SEP> -NHC2H4OCH5 <SEP> 200-202
<tb> <SEP> .CH3
<tb> -NH-C5H6OCH3 <SEP> 178-180 <SEP> -NH-C3H6O <SEP> CH <SEP> 155-157
<tb> <SEP> yC2H5 <SEP> CH3
<tb> -NH-C2H4N <SEP> 156-158 <SEP> -NH-C2H5 <SEP> 205-206
<tb> <SEP> C2H5
<tb>

Claims (1)

PATENTANSPRUCH Verfahren zur Herstellung neuer Pyrimidine der Formel EMI2.2 in welcher R1 eine durch einen oder zwei aliphatische Reste substituierte Aminogruppe, R2 Alkyl und R3 Wasserstoff oder niederes Alkyl bedeutet, dadurch gekennzeichnet, dass man ein substituiertes Guanidin der Formel EMI2.3 mit einem Dialkylester einer Alkoxymethylenmalonsäure oder einer a-Alkoxyalkylidenmalonsäure umsetzt. PATENT CLAIM Process for the preparation of new pyrimidines of the formula EMI2.2 in which R1 is an amino group substituted by one or two aliphatic radicals, R2 is alkyl and R3 is hydrogen or lower alkyl, characterized in that a substituted guanidine of the formula EMI2.3 with a dialkyl ester of an alkoxymethylene malonic acid or an α-alkoxyalkylidene malonic acid.
CH361283D 1957-07-12 1957-07-12 Process for the preparation of new pyrimidines CH361283A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH361283T 1957-07-12
CH358424T 1957-07-12

Publications (1)

Publication Number Publication Date
CH361283A true CH361283A (en) 1962-04-15

Family

ID=25737218

Family Applications (1)

Application Number Title Priority Date Filing Date
CH361283D CH361283A (en) 1957-07-12 1957-07-12 Process for the preparation of new pyrimidines

Country Status (1)

Country Link
CH (1) CH361283A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013163159A3 (en) * 2012-04-24 2014-01-16 Board Of Trustees Of Northern Illinois University Design and synthesis of novel inhibitors of isoprenoid biosynthesis
US10155766B2 (en) 2016-06-14 2018-12-18 Board Of Trustees Of Northern Illinois University Pyrazolopyrimidine antibacterial agents

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013163159A3 (en) * 2012-04-24 2014-01-16 Board Of Trustees Of Northern Illinois University Design and synthesis of novel inhibitors of isoprenoid biosynthesis
US9309232B2 (en) 2012-04-24 2016-04-12 Board Of Trustees Of Northern Illinois University Synthesis of novel inhibitors of isoprenoid biosynthesis
EP2841070B1 (en) * 2012-04-24 2018-07-25 Board Of Trustees Of Northern Illinois University Design and synthesis of novel inhibitors of isoprenoid biosynthesis
US10155766B2 (en) 2016-06-14 2018-12-18 Board Of Trustees Of Northern Illinois University Pyrazolopyrimidine antibacterial agents

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