DE1770099A1 - Process for the preparation of pyrazolo- (3,4-d) -pyrimidines, which can optionally be substituted in the 1,4,6-position - Google Patents
Process for the preparation of pyrazolo- (3,4-d) -pyrimidines, which can optionally be substituted in the 1,4,6-positionInfo
- Publication number
- DE1770099A1 DE1770099A1 DE19681770099 DE1770099A DE1770099A1 DE 1770099 A1 DE1770099 A1 DE 1770099A1 DE 19681770099 DE19681770099 DE 19681770099 DE 1770099 A DE1770099 A DE 1770099A DE 1770099 A1 DE1770099 A1 DE 1770099A1
- Authority
- DE
- Germany
- Prior art keywords
- reaction
- optionally
- carried out
- pyrazolo
- acid
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims description 16
- 238000002360 preparation method Methods 0.000 title claims description 4
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical class C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 150000001408 amides Chemical class 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 150000001299 aldehydes Chemical class 0.000 claims description 2
- 239000003701 inert diluent Substances 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- 239000000155 melt Substances 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims 1
- HIOHRZIAENJDHP-UHFFFAOYSA-N CC(O)=O.N#CC#N Chemical compound CC(O)=O.N#CC#N HIOHRZIAENJDHP-UHFFFAOYSA-N 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 claims 1
- 239000004927 clay Substances 0.000 claims 1
- 238000001816 cooling Methods 0.000 claims 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims 1
- 239000005457 ice water Substances 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 238000009835 boiling Methods 0.000 description 5
- 150000002429 hydrazines Chemical class 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- -1 des Acid amides Chemical class 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 125000003500 enol ether group Chemical class 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000003217 pyrazoles Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 description 1
- OFXFRDYGWYPETE-UHFFFAOYSA-N C(C)C(OCC)(OC#N)OC#N Chemical compound C(C)C(OCC)(OC#N)OC#N OFXFRDYGWYPETE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 125000004036 acetal group Chemical group 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000001470 diamides Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001240 enamine group Chemical group 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000649 purine antagonist Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000003369 theophyllinelike Effects 0.000 description 1
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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Catalysts (AREA)
Description
ZELLSTOFFFABRIK WALDHOF Mannheim, den 30.3.1968PULP FACTORY WALDHOF Mannheim, March 30, 1968
Dr.VdB./Kl. (O.N. 67O)Dr VdB./Kl. (O.N. 67O)
Verfahren zur Herstellung von Pyrazolo-(3,4-d)-p'yrimidinen, die gegebenenfalls in 1,4,6-Stellung substituiert sein können.Process for the preparation of pyrazolo- (3,4-d) -p'yrimidinen, which can optionally be substituted in the 1,4,6-position.
Pyrazolo-(3»4-d)-pyrimidine, insbesondere das 4-Hydroxy-pyrazolo-(3t4-d)-pyrimidine/, sind als Arzneimittel mit eof fein- und theophyllinartiger Wirkung bekannt· Besondere Bedeutung kommt diesen Substanzen als Purinantagonisten und zur Behandlung von Gicht zu. Bei der Synthese dieser Substanzen verwendete man bisher ein zweistufiges Verfahren, d.h. man mußte erst ein geeignetes Pyrazolderivat herstellen, um daraus durch Umsetzung mit geeigneten Säureamiden in einer gesonderten Reaktion die erwünschten Arzneimittel herzustellen. Derar.tige Verfahren sind beispielsweise in der Deutschen Patentschrift I0O70.635 beschrieben. Diesen bekannten Verfahren haften jedoch Schwierigkeiten an, weil man erst eine umständliche Isolierung und Reinigung der als Zwischenprodukte benötigten Pyrazole durchführen mußte, ehe die weitere Umsetzung mit den Säureamiden stattfinden konnte.Pyrazolo- (3 »4-d) -pyrimidines, especially 4-hydroxy-pyrazolo- (3t4-d) -pyrimidines / , are known as drugs with a fine- and theophylline-like effect. These substances are of particular importance as purine antagonists Treatment of gout too. In the synthesis of these substances, a two-step process has been used up to now, ie a suitable pyrazole derivative first had to be produced in order to produce the desired medicament therefrom by reaction with suitable acid amides in a separate reaction. Such processes are described, for example, in German patent specification 10O70.635. However, difficulties are attached to these known processes because the laborious isolation and purification of the pyrazoles required as intermediate products first had to be carried out before the further reaction with the acid amides could take place.
Ss galt daher die Aufgabe zu lösen, die bisherigen Verfahrensweisen zu vereinfachen.So the task to be solved was to follow the previous procedures simplify.
Als Lösung dieser Aufgabe wird ein Verfahren zur Herstellung von Pyrazolo-(3»4-d)-pyrimidinen gesehen, die gegebenenfalls in 1,4»6-Stellung substituiert sein können mit dem kennzeichnenden Merkmal, daß man <X -Oyan-^-formylessigsäuren, gegebenenfalls in Form ihrer funktionellen Säure- u./oder Aldehydderivate, wobei in χ Stellung ein Wasserstoffatom stehen muß, mit an den Stickstoffatomen mindestens 3 Wasserstoffatomβ tragenden Hydrazinen und einem Säureamid bei Temperaturen über I50 umsetst. The solution to this problem is a process for the preparation of pyrazolo- (3 »4-d) -pyrimidines, which can optionally be substituted in the 1,4» 6-position with the characteristic feature that one <X -Oyan - ^ - formyl acetic acids, optionally in the form of their functional acid and / or aldehyde derivatives, where a hydrogen atom must be in the χ position, with hydrazines carrying at least 3 hydrogen atoms on the nitrogen atoms and an acid amide at temperatures above 150.
2098U/1621 ./.2098U / 1621 ./.
SAD ORiGSNALSAD ORiGSNAL
Bei der Reaktionsfähigkeit sowohl der c-Cyan- χ,-f ormylessigsäure oder deren Derivate als auch des Hydrazins bzw. Hydrazinderivate als auch des Säureamids war es in höchstem Maße überraschend, daß die Umsetzung dieser 3 Verbindungstypen in einer Reaktion, d.h. in einem einstufigen Verfahren zu den entsprechenden Pyrazolo-(3,4-d)-pyrimidinen in hoher Ausbeute bzw. praktisch quantitativ fü?h r t. Dieses Ergebnis war auch insofern nicht vorauszusehen, als bei relativ hohen Temperaturen gearbeitet wird. Unter derartigen Bedingungen können erhebliche Verschiebungen bezüglich der Aktivität der einzelnen reaktionsfähigen Gruppen auftreten, sodaß nicht vorausgesagt werden konnte, ob eventuell andere Reaktioneverlaufe stattfinden.With the reactivity of both c-cyano- χ, -formylacetic acid or their derivatives as well as hydrazine or hydrazine derivatives as well as des Acid amides it was extremely surprising that the implementation of this 3 types of compounds in one reaction, i.e. in a one-step process to the corresponding pyrazolo- (3,4-d) -pyrimidines in high yield or practically quantitatively leads. This result was also insofar not foreseen when working at relatively high temperatures. Under such conditions there can be significant shifts in relation to the activity of the individual reactive groups occur, so that it could not be predicted whether other reactions might take place occur.
Als Ausgangssubstanzen für das Verfahren nach vorliegender Erfindung kommen neben χ -Cyan- \>formyles3ig8äure die entsprechenden funktioneilen Säurederivate, insbesondere die Ester, wie Methylester, Äthylester, Butkyleeter, Hexylester, Isopropylester, Phenylester, p-Chlorphenylester, p-Nitrophenylester, Benzylester o.dgl., ferner Nitrile, Säureamide, deren Afflidwasserstoffatome, teilweise oder vollständig ersetzt sein können durch Methyl-, Äthyl-, Hydroxyäthyl-Reste in Betracht. Unter derartigen Verbindungen sind als besonders bevorzugt Äthoxymethylencyaneesigsäureäthylester, Äthoxymethylenmalonsäuredinitril zu nennen, bei denen also auch die Formyl-Gruppe in Form einer Enoläther-Gruppe vorliegt. Des weiteren ist es möglich, anstelle der Enoläther-Gruppierung die Enamin-Gruppierung, die Acetal-Gruppierung und die Mercaptal-Gruppierung zu verwenden.As starting substances for the process according to the present invention In addition to χ -cyano- \> formyles3ig8 acid, there are the corresponding functional parts Acid derivatives, especially the esters, such as methyl esters, ethyl esters, butkyl esters, hexyl esters, isopropyl esters, phenyl esters, p-chlorophenyl esters, p-Nitrophenyl esters, benzyl esters or the like, also nitriles, acid amides, their Afflid hydrogen atoms, can be partially or completely replaced by methyl, ethyl, hydroxyethyl radicals into consideration. Among such Compounds that are particularly preferred are ethyl ethoxymethylene cyanate, ethoxymethylene malononitrile, which means that the formyl group is also present in the form of an enol ether group. It is also possible to use the enamine group, the acetal group and the mercaptal group instead of the enol ether group.
Bei den Hydrazinen, die als weitere Ausgangssubstanzen bei dem Verfahren nach vorliegender Erfindung in Betracht kommen, handelt es sich um solche Hydrazine, die mindestens 3 Wasserstoffatome an den Stickstoffatomen aufweisen. Neben Hydrazin werden auch Monoalkyl- und Monoarylhydrazine verwendet, deren Kohlenwasserstoff-Reste 1-10 Kohlenstoffatome aufweisen. Die Monoarylhydrazine können auch in der Arylgruppe durch Halogenatome substituiert sein.In the case of the hydrazines, which are used as further starting substances in the process come into consideration according to the present invention, it is such Hydrazines that have at least 3 hydrogen atoms on the nitrogen atoms. In addition to hydrazine, monoalkyl and monoaryl hydrazines are also used, the hydrocarbon radicals of which have 1-10 carbon atoms. The monoarylhydrazines can also be in the aryl group through halogen atoms be substituted.
2098U/16212098U / 1621
Als dritter Reaktionspartner werden Säureamide, insbesondere Säureamide aliphatischer oder aromatischer Carbonsäure wie Formamid, Acetamid, aber auoh Diamide wie Harnstoff, Thioharnstoff, Guanidine, ferner die entsprechenden Amidine verwendet.Acid amides, in particular acid amides, are used as the third reaction partner aliphatic or aromatic carboxylic acid such as formamide, acetamide, but also diamides such as urea, thiourea, guanidines, and also the corresponding amidines are used.
Nach dem Verfahren vorliegender Erfindung werden die drei Reaktionspartner gleichzeitig oder nach einander in ein Reaktionsgefäß gegeben und anschließend auf Temperaturen ab 150 erhitzt« Vorzugsweise verwendet man einen Überschuß an dem Säureamid, das gleichzeitig als Lösungsmittel für die beiden anderen Reaktionspartner dient. Des weiteren ist es möglich, ^j beim Siedepunkt des Säureamids die Reaktion ablaufen zu lassen. Des weiteren wurde gefunden, daß man die Umsetzung auch in einer Schmelze des Säureamids durchführen kann. Hierbei ist lediglich zu beachten, daß bei den gewählten Temperaturen keine Zersetzung der Reaktionspartner eintritt. Falls eine derartige Möglichkeit bestehen sollte, hat es sich weiterhin als vorteilhaft herausgestellt, die Umsetzung in Gegenwart eines weiteren inerten Verdünnungs- u./oder Lösungsmittels durchzuführen, dessen Siedepunkt oberhalb 150 liegt. Unter den Lösungs- bzw. Verdünnungsmitteln kommen höhersiedende ein-, zwei- oder mehrwertige Alkohole, Dirnethylsulfoxyd hochsiedende Äther und hochsiedende Kohlenwasserstoffe infrage. In manchen Fällen kann es angezeigt sein, zur Beschleunigung der Reaktion geringe Mengen von Alkalimetallalkoholaten mitzuverwenden, die sich von -den Alkalimetallen, insbesondere von Lithium, Natrium, Kalium ableiten.According to the method of the present invention, the three reactants are added to a reaction vessel simultaneously or one after the other and then heated to temperatures above 150 «Preferably used one has an excess of the acid amide, which is also used as a solvent serves for the other two reactants. It is also possible to add ^ j to allow the reaction to proceed at the boiling point of the acid amide. It has also been found that the reaction can also be carried out in a melt Acid amides can perform. It is only necessary to ensure that no decomposition of the reactants occurs at the selected temperatures. If there is such a possibility, it still has found to be advantageous to carry out the reaction in the presence of a further inert diluent and / or solvent whose boiling point is above 150. Among the solvents and thinners higher-boiling monohydric, dihydric or polyhydric alcohols, dirnethyl sulfoxide, high-boiling ethers and high-boiling hydrocarbons are possible. In In some cases it may be indicated to speed up the response to use small amounts of alkali metal alcoholates, which are derived from the alkali metals, in particular from lithium, sodium, potassium.
Die Reaktionsprodukte nach vorliegender Erfindung fallen in hoher Reinheit und in einer ausgezeichneten Ausbeute an. Sie sind in der Regel nach einmaliger Umkristallisation chromatographisch rein.The reaction products according to the present invention are obtained in high purity and in excellent yield. They are usually after single recrystallization chromatographically pure.
Anhand der nachstehenden Beispiele wird das Verfahren nach vorliegender Erfindung näher erläutert.The following examples illustrate the process of the present invention Invention explained in more detail.
2098U/16212098U / 1621
Claims (1)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19681770099 DE1770099C3 (en) | 1968-04-01 | Process for the preparation of pyrazoles square brackets to 3,4-square brackets to pyrimidines | |
| CH393969A CH520154A (en) | 1968-04-01 | 1969-03-17 | Process for the preparation of pyrazolo- (3,4-d) -pyrimidines, which may optionally be substituted in the 1,4,6-position |
| IT1462769A IT1061789B (en) | 1968-04-01 | 1969-03-26 | PROCEDURE FOR THE PRODUCTION OF PIRAZOLO- (3 4-D) -PIRIMIDINE POSSIBLY REPLACED IN THE POSITION- 1 4 6 |
| GB1230289D GB1230289A (en) | 1968-04-01 | 1969-03-28 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19681770099 DE1770099C3 (en) | 1968-04-01 | Process for the preparation of pyrazoles square brackets to 3,4-square brackets to pyrimidines |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE1770099A1 true DE1770099A1 (en) | 1972-03-30 |
| DE1770099B2 DE1770099B2 (en) | 1975-11-20 |
| DE1770099C3 DE1770099C3 (en) | 1976-07-08 |
Family
ID=
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4277418A (en) * | 1976-08-10 | 1981-07-07 | Dynamit Nobel Aktiengesellschaft | Method of preparing alkoxymethylene compounds |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4277418A (en) * | 1976-08-10 | 1981-07-07 | Dynamit Nobel Aktiengesellschaft | Method of preparing alkoxymethylene compounds |
| US4468353A (en) * | 1976-08-10 | 1984-08-28 | Dynamit Nobel Ag | Method of preparing alkoxymethylene compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| IT1061789B (en) | 1983-04-30 |
| DE1770099B2 (en) | 1975-11-20 |
| GB1230289A (en) | 1971-04-28 |
| CH520154A (en) | 1972-03-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CH493528A (en) | 2-(phenylamino or pyridylamino)-pyrimidines anti- - inflammatory antipyretic | |
| DE1922702A1 (en) | Process for the preparation of 1-glycosyl-5-azacytosines | |
| DE1904894C3 (en) | Process for the preparation of 3-amino-4-carboxamido-pyrazoles | |
| DE1770099A1 (en) | Process for the preparation of pyrazolo- (3,4-d) -pyrimidines, which can optionally be substituted in the 1,4,6-position | |
| DE2065714A1 (en) | NEW BENZODIAZE PINE DERIVATIVES | |
| DE1770099C3 (en) | Process for the preparation of pyrazoles square brackets to 3,4-square brackets to pyrimidines | |
| DE2121694A1 (en) | Novel S-triazine derivatives and their salts and processes for their preparation | |
| DE812316C (en) | Process for the preparation of 2- (p-aminobenzenesulfonamido) -4-methylpyrimidine | |
| DE2453365A1 (en) | METHOD FOR PRODUCING N-TRIMETHYLSILYL ACETAMIDE | |
| DE2527157C2 (en) | Process for the preparation of 2-formylquinoxaline-N → 1 →, N → 4 → -dioxide dimethylacetal | |
| DE574944C (en) | Process for the preparation of 3, 4, 5-trisubstituted 1, 2, 4-triazoles | |
| DE1921340C3 (en) | 2-Phenyl-5-halo-pyrimidines substituted in the 4-position | |
| DE2117050C3 (en) | Process for the preparation of 1- (5-nitrothiazol-2-yl) -2-oxotetrahydroimidazole | |
| AT284126B (en) | Process for the preparation of new substituted aminopyrimidines and their salts and optically active isomers | |
| AT216511B (en) | Process for the preparation of 1,2,4-benzothiadiazine-1,1-dioxide compounds | |
| AT363950B (en) | METHOD FOR PRODUCING 2,4-DIAMINO-5-BENZYLPYRIMIDINE | |
| DE1470163C (en) | Process for the preparation of 3,3-ethylenebis (tetrahydro-4,6-dimethyl-2Hl, 3,5-thiadiazine-2-thione) | |
| DE2015650A1 (en) | omega-guanidinoamide derivatives and their onium salts | |
| DE1940704C3 (en) | Process for the preparation of 2-mercaptoinosine | |
| DE1200308B (en) | Process for the preparation of 4,6-dihydroxypyrimidines | |
| DE736024C (en) | Process for the production of oxygen-containing anthracene fragments | |
| DE1085879B (en) | Process for the production of salicylic acid-O-acetic acid-imide | |
| DE2940037A1 (en) | MONOMERIC N-METHYLENE AMINOACETONITRILE AND METHOD FOR THE PRODUCTION THEREOF | |
| DE2750661A1 (en) | 3,4,6-tri:chloro-phthalimide prodn. - from tetra:chloro-cyclohexadiene-di:carboxylate, useful intermediate for pesticides, pharmaceuticals, dyes etc. | |
| DE1186466B (en) | Process for the preparation of 4, 6-dioxo-4, 5, 6, 7-tetrahydropyrazolo [3, 4-d] pyrimidines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) | ||
| E77 | Valid patent as to the heymanns-index 1977 | ||
| EHJ | Ceased/non-payment of the annual fee |