DE1082267B - Process for the preparation of new derivatives of pyrimidine - Google Patents
Process for the preparation of new derivatives of pyrimidineInfo
- Publication number
- DE1082267B DE1082267B DES30698A DES0030698A DE1082267B DE 1082267 B DE1082267 B DE 1082267B DE S30698 A DES30698 A DE S30698A DE S0030698 A DES0030698 A DE S0030698A DE 1082267 B DE1082267 B DE 1082267B
- Authority
- DE
- Germany
- Prior art keywords
- pyrimidine
- ethyl
- preparation
- chlorophenyl
- chloro
- 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 6
- 238000002360 preparation method Methods 0.000 title claims description 5
- 150000003230 pyrimidines Chemical class 0.000 title claims description 4
- NCBKXYRDZOQBRI-UHFFFAOYSA-N 4-chloro-5-(4-chlorophenyl)-6-ethylpyrimidin-2-amine Chemical compound CCC1=NC(N)=NC(Cl)=C1C1=CC=C(Cl)C=C1 NCBKXYRDZOQBRI-UHFFFAOYSA-N 0.000 claims description 5
- 150000003141 primary amines Chemical class 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- WPWHSFAFEBZWBB-UHFFFAOYSA-N 1-butyl radical Chemical compound [CH2]CCC WPWHSFAFEBZWBB-UHFFFAOYSA-N 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 claims 1
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- AWELPWWKICQBQP-UHFFFAOYSA-N 4-N-butyl-5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine Chemical compound NC1=NC(=C(C(=N1)NCCCC)C1=CC=C(C=C1)Cl)CC AWELPWWKICQBQP-UHFFFAOYSA-N 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
- OEVCQPRLPSNHFQ-UHFFFAOYSA-N N-[4-chloro-5-(4-chlorophenyl)-6-ethylpyrimidin-2-yl]acetamide Chemical compound C(C)(=O)NC1=NC(=C(C(=N1)Cl)C1=CC=C(C=C1)Cl)CC OEVCQPRLPSNHFQ-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- GTRNSMDMAHHXRT-UHFFFAOYSA-N ClO.C(CCC)N Chemical compound ClO.C(CCC)N GTRNSMDMAHHXRT-UHFFFAOYSA-N 0.000 description 1
- 241000224017 Plasmodium berghei Species 0.000 description 1
- -1 aliphatic amines Chemical class 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
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
- C07D239/48—Two nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von neuen Derivaten des Pyrimidins Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von neuen Derivaten des Pyrimidins der allgemeinen Formel worin R den Rest n-C, He oder - (CH,), - C H (C H3) 2 bedeutet.Process for the preparation of new derivatives of pyrimidine The present invention relates to a process for the preparation of new derivatives of pyrimidine of the general formula where R denotes the radical nC, He or - (CH,), - CH (C H3) 2.
Diese Produkte werden erfindungsgemäß erhalten, indem man ein primäres Amin R - N 112 auf 2-Amino-4-chlor-5-(4'-chlor-phenyl)-6-äthyl-pyrimidin oder sein N-acetyliertes Derivat, nämlich 2-Acetylamino-4-chlor-5-(4'-chlor-phenyl)-6-äthyl-pyrimidin, einwirken läßt; im letztgenannten Falle findet gleichzeitig Entacetylierung des Acetylaminorestes statt.According to the invention, these products are obtained by using a primary Amine R - N 112 on 2-amino-4-chloro-5- (4'-chloro-phenyl) -6-ethyl-pyrimidine or be N-acetylated derivative, namely 2-acetylamino-4-chloro-5- (4'-chlorophenyl) -6-ethyl-pyrimidine, lets act; in the latter case, deacetylation of the takes place at the same time Acetylaminorestes instead.
Die Umsetzung wird durchgeführt, indem man auf Temperaturen über 100°C, vorzugsweise zwischen 150 und 200°C, erhitzt. Vorteilhaft wird ein Überschuß an primärem Amin verwendet; bei Verwendung von niedrigen aliphatischen Aminen arbeitet man im Autoklav, im Falle von Aminen mit genügend hohem Siedepunkt unter Erhitzen am Rückflußkühler.The reaction is carried out by heating to temperatures above 100 ° C, preferably between 150 and 200 ° C, heated. An excess of is advantageous primary amine used; works when using lower aliphatic amines one in the autoclave, in the case of amines with a sufficiently high boiling point with heating on the reflux condenser.
Es ist auch möglich, die Umsetzung des 2-Amino-4-chlor-5-(4'-chlor-phenyl)-6-äthyl-pyrimidins nicht nur mit einem primären Amin R - N H2, sondern auch mit einem Salz derartiger Amine, wie z. B. dem Hydrochlorid oder dem Acetat, durchzuführen. In diesem Fall kann man ohne Lösungsmittel bei einer Temperatur über 150°C und vorzugsweise bei etwa 200°C arbeiten. Diese Methode weist im besonderen den Vorteil auf, daß man in allen Fällen ohne Autoklav arbeiten kann.It is also possible to implement the 2-amino-4-chloro-5- (4'-chlorophenyl) -6-ethyl-pyrimidine not only with a primary amine R - N H2, but also with a salt of such Amines such as B. the hydrochloride or the acetate to perform. In this case can be used without a solvent at a temperature above 150 ° C and preferably at work around 200 ° C. This method has the particular advantage that one can work without an autoclave in all cases.
Die Herstellung des als Ausgangsmaterial verwendeten 2-Amino-4-chlor-5-(4'-chlor-phenyl)-6-äthyl-pyrimidins bzw. seines N-acetylierten Derivats ist in der Patentanmeldung S 28810 IVc/12p beschrieben.The preparation of the 2-amino-4-chloro-5- (4'-chlorophenyl) -6-ethyl-pyrimidine used as starting material or its N-acetylated derivative is described in patent application S 28810 IVc / 12p.
Die erfindungsgemäß erhaltenen Produkte besitzen interessante antiparasitäre Eigenschaften; insbesondere auf Grund ihrer Antimalariawirksamkeit sind sie in der Human- und Veterinärtherapie verwendbar.The products obtained according to the invention have interesting anti-parasitic properties Properties; especially because of their antimalarial effectiveness, they are in the Can be used in human and veterinary therapy.
In der untenstehenden Tabelle sind die chemotherapeutischen Eigenschaften
der erfindungsgemäß hergestellten Substanzen mit denjenigen des bekannten 2,4-Diamino-5-(4'-chlor-phenyl)-6-äthyl
pyrimidins verglichen:
In analoger Weise kann man das 2-Amino-4-(3'-rnethylbutylamino) - 5 - (4"- chlor - phenyl) - 6 - äthyl - pyrimidin vom F. = 143°C erhalten. Beispiel 2 2 g 2-Amino-4-chlor-5-(4'-chlor-phenyl)-6-äthyl-pyrimidin vom F. =163°C und 1,26 g n-Butylarnin-chlorhydrat werden 1 Stunde auf 200°C erhitzt. Man nimmt die erhaltene Masse in Wasser auf, wäscht mit Wasser und trocknet im Vakuum. Man erhält 2,1 g rohes 2-Amino-4-n-butylamino-5- (4'-chlor-phenyl) -6-äthyl-pyrimidin vom F. = 120 bis 122°C. Nach dem Umkristallisieren aus Dioxan ist dieses Produkt rein und schmilzt bei 132 bis 133°C.The 2-amino-4- (3'-methylbutylamino) - 5 - (4 "- chlorophenyl) - 6 - ethyl - pyrimidine obtained with a melting point of 143 ° C. Example 2 2 g of 2-amino-4-chloro-5- (4'-chloro-phenyl) -6-ethyl-pyrimidine with a melting point of 163 ° C and 1.26 g of n-butylamine chlorohydrate are heated to 200 ° C. for 1 hour. One takes the one received The mass is dissolved in water, washed with water and dried in vacuo. 2.1 g are obtained Crude 2-amino-4-n-butylamino-5- (4'-chlorophenyl) -6-ethyl-pyrimidine with a melting point of 120 up to 122 ° C. After recrystallization from dioxane, this product is pure and melts at 132 to 133 ° C.
In analoger Weise kann man das 2-Amino-4-(3'-methylbutylamino)-5-(4"-chlor-phenyl)-6-äthyl-pyrimidin vom F. =143°C erhalten.2-Amino-4- (3'-methylbutylamino) -5- (4 "-chlorophenyl) -6-ethyl-pyrimidine can be used in an analogous manner obtained from the F. = 143 ° C.
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1082267X | 1951-11-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1082267B true DE1082267B (en) | 1960-05-25 |
Family
ID=9610612
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DES30698A Pending DE1082267B (en) | 1951-11-06 | 1952-10-16 | Process for the preparation of new derivatives of pyrimidine |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1082267B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB583815A (en) * | 1944-05-18 | 1946-12-31 | Francis Henry Swinden Curd | New pyrimidine compounds |
-
1952
- 1952-10-16 DE DES30698A patent/DE1082267B/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB583815A (en) * | 1944-05-18 | 1946-12-31 | Francis Henry Swinden Curd | New pyrimidine compounds |
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