CH361283A - Process for the preparation of new pyrimidines - Google Patents
Process for the preparation of new pyrimidinesInfo
- 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
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)
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)
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 |
-
1957
- 1957-07-12 CH CH361283D patent/CH361283A/en unknown
Cited By (4)
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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