DE1122533B - Process for the preparation of basic substituted 4-amino-6-hydroxypyrimidines - Google Patents
Process for the preparation of basic substituted 4-amino-6-hydroxypyrimidinesInfo
- Publication number
- DE1122533B DE1122533B DEK37507A DEK0037507A DE1122533B DE 1122533 B DE1122533 B DE 1122533B DE K37507 A DEK37507 A DE K37507A DE K0037507 A DEK0037507 A DE K0037507A DE 1122533 B DE1122533 B DE 1122533B
- Authority
- DE
- Germany
- Prior art keywords
- amino
- general formula
- basic
- hydroxypyrimidines
- basic substituted
- 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 5
- HFMLLTVIMFEQRE-UHFFFAOYSA-N 6-amino-1h-pyrimidin-4-one Chemical class NC1=CC(O)=NC=N1 HFMLLTVIMFEQRE-UHFFFAOYSA-N 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 4
- -1 alkyl radicals Chemical class 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 7
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical class OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 150000005840 aryl radicals Chemical group 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 2
- 150000003254 radicals Chemical class 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 6
- 230000036772 blood pressure Effects 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 150000001409 amidines Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
- MLIREBYILWEBDM-UHFFFAOYSA-M 2-cyanoacetate Chemical compound [O-]C(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-M 0.000 description 1
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 1
- JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 1
- UBSBLGBWNYUPDW-UHFFFAOYSA-N 2-phenylethanimidamide;hydrochloride Chemical compound Cl.NC(=N)CC1=CC=CC=C1 UBSBLGBWNYUPDW-UHFFFAOYSA-N 0.000 description 1
- SNIKHWKRGVRMQG-UHFFFAOYSA-N 5-(2-aminoethyl)-2-methylpyrimidin-4-amine Chemical compound CC1=NC=C(CCN)C(N)=N1 SNIKHWKRGVRMQG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 208000036029 Uterine contractions during pregnancy Diseases 0.000 description 1
- OMOVVBIIQSXZSZ-UHFFFAOYSA-N [6-(4-acetyloxy-5,9a-dimethyl-2,7-dioxo-4,5a,6,9-tetrahydro-3h-pyrano[3,4-b]oxepin-5-yl)-5-formyloxy-3-(furan-3-yl)-3a-methyl-7-methylidene-1a,2,3,4,5,6-hexahydroindeno[1,7a-b]oxiren-4-yl] 2-hydroxy-3-methylpentanoate Chemical compound CC12C(OC(=O)C(O)C(C)CC)C(OC=O)C(C3(C)C(CC(=O)OC4(C)COC(=O)CC43)OC(C)=O)C(=C)C32OC3CC1C=1C=COC=1 OMOVVBIIQSXZSZ-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- NDEMNVPZDAFUKN-UHFFFAOYSA-N guanidine;nitric acid Chemical compound NC(N)=N.O[N+]([O-])=O.O[N+]([O-])=O NDEMNVPZDAFUKN-UHFFFAOYSA-N 0.000 description 1
- 239000005555 hypertensive agent Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001020 rhythmical effect Effects 0.000 description 1
- 238000009938 salting Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 125000005853 β-dimethylaminoethyl group Chemical group 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
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- 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 basisch substituierter 4-Amino-6-hydroxypyrimidine Gegenstand der Erfindung ist ein Verfahren zur Herstellung basisch substituierter 4-Amino-6-hydroxypyrimidine der allgemeinen Formel bzw. deren Salzen oder quartären Ammoniumverbindungen, in welcher R ein Wasserstoffatom oder einen Alkyl-, Cycloalkyl-, Aralkyl- oder Arylrest oder eine Aminogruppe, R, und R2 niedermolekulare Alkylreste oder Cycloalkyl-, Aralkyl- bzw. Arylgruppen oder auch zusammen mit dem Stickstoffatom einen Piperidino-, Pyrrolidino-, Morpholino- oder Piperazinoring bedeuten, die Reste R3 Wasserstoffatome darstellen oder zum Teil auch die Bedeutung von R haben und n die Zahl 2, 3 oder 4 bedeutet, dadurch gekennzeichnet, daß man Verbindungen der allgemeinen Formel bzw. deren Salze mit basisch substituierten Cyanessigsäureestern der allgemeinen Formel wobei R4 einen niedermolekularen Alkylrest bedeutet, in Gegenwart oder Abwesenheit von basischen Mitteln und/oder Lösungsmitteln kondensiert.Process for the preparation of basic substituted 4-amino-6-hydroxypyrimidines The invention relates to a process for the preparation of basic substituted 4-amino-6-hydroxypyrimidines of the general formula or their salts or quaternary ammonium compounds in which R is a hydrogen atom or an alkyl, cycloalkyl, aralkyl or aryl radical or an amino group, R and R2 are low molecular weight alkyl radicals or cycloalkyl, aralkyl or aryl groups or together with the nitrogen atom denote a piperidino, pyrrolidino, morpholino or piperazine ring, the radicals R3 represent hydrogen atoms or in some cases also have the meaning of R and n denotes the number 2, 3 or 4, characterized in that compounds of the general formula or their salts with basic substituted cyanoacetic acid esters of the general formula where R4 is a low molecular weight alkyl radical, condensed in the presence or absence of basic agents and / or solvents.
Als basisch substituierte Cyanessigsäureester kommen beispielsweise in Betracht: n-(B"-Dimethylamino äthyl) - cyanessigsäureäthylester, es - (y '- Diäthylaminopropyl)-cyanessigsäureäthylester, oc-(ß'-Dibutylaminoäthyl) - cyanessigsäuremethylester, A - (ß' - Piperidinoäthyl) - cyanessigsäureäthylester, ou - - Phenyl - - diäthylaminoäthyl) - cyanessigsäureäthylester oder a-(fl'-N.Methyl.N-benzylaminoäthyl).cyanessigsäure. propylester. As basic substituted cyanoacetic acid esters, for example into consideration: n- (B "-Dimethylamino ethyl) - ethyl cyanoacetate, es - (y '- diethylaminopropyl) -cyanoacetic acid ethyl ester, oc- (ß'-dibutylaminoethyl) - methyl cyanoacetate, A - (ß '- piperidinoethyl) - ethyl cyanoacetate, ou - - phenyl - - diethylaminoethyl) - ethyl cyanoacetate or a- (fl'-N.Methyl.N-benzylaminoethyl) .cyanoacetic acid. propyl ester.
Die Reaktion der basisch substituierten Cyanessigsäureester mit den Salzen von Amidinen erfolgt in organischen Lösungsmitteln und in Gegenwart basischer Kondensationsmittel, wie Alkalialkoholat Natriumamid, Ätzalkali oder Alkalicarbonat. In einigen Fällen ist es auch möglich, die Umsetzung in Abwesenheit von Lösungsmitteln durchzuführen. The reaction of the basic substituted cyanoacetic acid ester with the Salting of amidines takes place in organic solvents and in the presence of basic solvents Condensing agents, such as alkali metal alcoholate, sodium amide, caustic alkali or alkali metal carbonate. In In some cases it is also possible to carry out the reaction in the absence of solvents perform.
Die Umsetzung findet bei Zimmertemperatur oder auch bei erhöhten Temperaturen bis zum Siedepunkt des Lösungsmittels statt. Werden an Stelle der Salze von Amidinen die freien Basen eingesetzt, so ist es unter Umständen auch möglich, die Kondensation in Abwesenheit basischer Mittel durchzuführen.The reaction takes place at room temperature or at elevated temperatures up to the boiling point of the solvent. Are used in place of the salts of amidines If the free bases are used, it is also possible under certain circumstances to carry out the condensation to be carried out in the absence of basic agents.
Es ist auch möglich, die erhaltenen Derivate des Pyrimidins nachträglich, z. B. vermittels Dialkylsulfat, Alkylhalogeniden oder Aralkylhalogeniden in die entsprechenden quartären Verbindungen zu überführen. It is also possible to use the derivatives of pyrimidine obtained subsequently, z. B. by means of dialkyl sulfate, alkyl halides or aralkyl halides in the to convert corresponding quaternary compounds.
Die neuen Verbindungen können als Arzneimittel oder als Zwischenprodukte für die Herstellung von Arzneimitteln Verwendung finden. The new compounds can be used as drugs or as intermediates for the manufacture of pharmaceuticals use.
Verglichen wurden die Substanzen: A 2 - Methyl -4-amino - 5 - (ß-di-n - butylaminoäthyl)-6-hydroxypyrimidin, B Verfahrensprodukt des Beispiels 5 der deutschen Patentschrift 671 787 (2-Methyl-4-amino-5-aminoäthylpyrimidin), C das in »Chemical Abstracts«, 1956, Sp. 13042h, referierte 2 - Methyl - 4 - amino .5 - (piperidinomethyl)-6-hydroxypyrimidin. The substances were compared: A 2 - methyl -4-amino - 5 - (ß-di-n - Butylaminoäthyl) -6-hydroxypyrimidine, B process product of Example 5 of the German Patent specification 671 787 (2-methyl-4-amino-5-aminoethylpyrimidine), C that in »Chemical Abstracts ”, 1956, Col. 13042h, reported 2 - methyl - 4 - amino.5 - (piperidinomethyl) -6-hydroxypyrimidine.
Geprüft wurde die Blutdruck-, Uterus- und Darmwirksamkeit der Substanzen. The blood pressure, uterus and intestinal effectiveness of the substances were tested.
Versuchstier . . Kaninchen Dosierung . 2 und 5 mg/kg Applikation .. . intravenös Die Versuche ergaben, daß die Substanz A in beiden Dosierungen bei guter allgemeiner Verträglichkeit praktisch ohne Beeinflussung des Blutdrucks rhythmische Uteruskontraktionen auslöst; auch die glatte Muskulatur des Darmes wird leicht erregt. Laboratory animal. . Rabbit dosage. 2 and 5 mg / kg application ... intravenous The experiments showed that the substance A in both Dosages with good general tolerance practically without influencing the Blood pressure triggers rhythmic uterine contractions; also the smooth muscles of the Gut is easily aroused.
Demgegenüber läßt die Substanz B alle diese Organsysteme bei Anwendung gleicher Dosen völlig unbeeinflußt. In contrast, substance B leaves all of these organ systems in use same doses completely unaffected.
Die Substanz C verursacht bereits bei einer Dosierung von 2 mg/kg einen starken Blutdruckabfall von 40 mm Hg und 10 Minuten Dauer. Bei Erhöhung der Dosis auf 5 mg/kg verlängerte sich die Zeit des Blutdruckabfalls auf etwa 25 Minuten. Die Schwere des Blutdruckabfalls machte eine Gabe von ß-(p-Oxyphenyfrisopropylmethylamin als blutdruckerhöhendes Mittel erforderlich, um das Versuchstier zu retten. Substance C already causes a dose of 2 mg / kg a sharp drop in blood pressure of 40 mm Hg for 10 minutes. When the Dose at 5 mg / kg extended the time of blood pressure drop to about 25 minutes. The severity of the drop in blood pressure made an administration of ß- (p-oxyphenyfrisopropylmethylamine required as a hypertensive agent to save the test animal.
Einen Einfluß auf den Uterus besitzt die Substanz C nicht, der Darm wird nur geringfügig erregt.Substance C has no influence on the uterus, the intestine is only slightly aroused.
Beispiel 1 26 g Acetamidin-H Cl werden in 75 ccm Methanol gelöst und die Lösung mit 47 g a-(ß'-Dimethylaminoäthyl)-cyanessigsäureäthylester (hergestellt aus Na-Cyanessigsäureäthylester und ß-Dimethylaminoäthylchlorid) versetzt. Die obige Mischung wird innerhalb einer Stunde bei Raumtemperatur zu 137 g 300/gel methanolischer Natriummethylatlösung zugetropft, der Ansatz anschließend 5 Stunden unter Rühren im Sieden gehalten und sodann etwa 150 ccm des Lösungsmittels abdestilliert. Die alkalische Lösung versetzt man mit 0,475 Mol konzentrierter Salzsäure, worauf sich aus der Lösung 2-MethylXamino-54ß'-dimethylaminoäthyl)6hydroxypyrimidin absetzt. Example 1 26 g of acetamidine-H Cl are dissolved in 75 cc of methanol and the solution with 47 g of a- (ß'-dimethylaminoethyl) -cyanacetic acid ethyl ester (prepared from Na-cyanoacetic acid ethyl ester and ß-dimethylaminoethyl chloride) added. The above Mixture becomes 137 g 300 / gel methanolic within one hour at room temperature Sodium methylate solution was added dropwise, and the batch was then stirred for 5 hours kept at the boil and then about 150 cc of the solvent was distilled off. the alkaline solution is mixed with 0.475 mol of concentrated hydrochloric acid, whereupon 2-MethylXamino-54ß'-dimethylaminoethyl) 6hydroxypyrimidine settles from the solution.
F. 217 bis 218"C (aus ethanol).F. 217-218 "C (from ethanol).
In entsprechender Weise erhält man 26 g Acetamidin-H CI und 54,2 g a-(ß'-Diäthylaminoäthyl)-cyanessigsäureäthylester - 2 - Methyl - 4 - amino-54ß-diäthylaminoäthyl}6-hydroxypyrimidin vom Schmelzpunkt 204"C. In a corresponding manner, 26 g of acetamidine-HCl and 54.2 are obtained g of ethyl a- (ß'-diethylaminoethyl) cyanoacetate - 2 - methyl - 4 - amino-54ß-diethylaminoethyl} 6-hydroxypyrimidine of melting point 204 "C.
Beispiel 2 21,5 g Benzamidin-H Cl in 50 ccm Methanol gelöst sowie 27,1 g a-(ß'-Mãthylaminoathyl)-cyanessigsäureäthylester werden langsam bei Raumtemperatur in 68,5 g einer 300/gen methanolischen Natriummethylatlösung getropft. Die Mischung wird 5 Stunden unter Rückflußkühlung im Sieden gehalten. Anschließend wird das Methanol abdestilliert, der Rückstand im Wasser gelöst und mit konzentrierter Salzsäure neutralisiert, wobei sich 2-Phenylffiamino-5-(ß-diäthylaminoathyl)-6-hydroxypyrimidin kristallin ausscheidet. F. 174"C. Example 2 21.5 g of benzamidine-H Cl dissolved in 50 cc of methanol and 27.1 g of a- (ß'-Mãthylaminoathyl) -cyanessigsäureäthylester are slowly at room temperature dropped into 68.5 g of a 300 / gen methanolic sodium methylate solution. The mixture is kept at the boil for 5 hours under reflux cooling. Then the methanol distilled off, the residue dissolved in water and neutralized with concentrated hydrochloric acid, 2-Phenylffiamino-5- (ß-diethylaminoathyl) -6-hydroxypyrimidine is crystalline ruled out. F. 174 "C.
Beispiel 3 Auf die gleiche Weise, wie im Beispiel 2 angegeben, erhält man aus 69,6 g Phenylacetamidin-HC1 und 81,5 g α,ß'-Diäthylaminoäthyl)-cyanessigsäureäthylester in Natriummethylatlösung 2-Benzyl-4-amino-5 - (ß - diäthylaminoäthyl) - 6 - hydroxypyrimidin vom Schmelzpunkt 174"C. Example 3 In the same manner as indicated in Example 2, obtained from 69.6 g of phenylacetamidine HC1 and 81.5 g of α, ß'-diethylaminoethyl) cyanoacetic acid ethyl ester in sodium methylate solution 2-benzyl-4-amino-5 - (ß - diethylaminoethyl) - 6 - hydroxypyrimidine of melting point 174 "C.
In entsprechender Weise erhält man aus 2-Phenylacetamidin-HCl und x -(B'- morpholinoäthyl)- cyanessigsäureäthylester 2-Benzyl-4-amino-5-(8-morpholinoäthyl)-6-hydroxypyrimidin. F. 270 C. In a corresponding manner, from 2-phenylacetamidine-HCl and x - (B'-morpholinoethyl) - ethyl cyanoacetate, 2-benzyl-4-amino-5- (8-morpholinoethyl) -6-hydroxypyrimidine. F. 270 C.
Aus Benzamidin-HC1 und ß-Morpholinoäthylcyanessigsäureäthylester wird 2-PhenylXamino-5-(ß-morpholinoäthyl)-6-hydroxypyrimidin vom Schmelzpunkt 245°C erhalten. From benzamidine HC1 and ß-Morpholinoäthylcyanessigsäureäthylester 2-PhenylXamino-5- (ß-morpholinoethyl) -6-hydroxypyrimidine has a melting point of 245 ° C obtain.
Beispiel 4 Auf die gleiche Weise, wie im Beispiel 2 angegeben, erhält man aus Guanidin-nitrat und a-(ß'-Dimethylaminoäthyl) - cyanessigsäureäthylester in Natriummethylat-Lösung 2,4 - Diamino - 5 - (ß - dimethylaminoäthyl)-6-hydroxypyrimidin. F. 238°C (als Dihydrochlorid). Example 4 In the same way as indicated in Example 2, obtained from guanidine nitrate and a- (ß'-dimethylaminoethyl) - ethyl cyanoacetate in sodium methylate solution 2,4 - diamino - 5 - (ß - dimethylaminoethyl) -6-hydroxypyrimidine. Mp 238 ° C (as dihydrochloride).
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK37507A DE1122533B (en) | 1959-04-18 | 1959-04-18 | Process for the preparation of basic substituted 4-amino-6-hydroxypyrimidines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK37507A DE1122533B (en) | 1959-04-18 | 1959-04-18 | Process for the preparation of basic substituted 4-amino-6-hydroxypyrimidines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1122533B true DE1122533B (en) | 1962-01-25 |
Family
ID=7221036
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEK37507A Pending DE1122533B (en) | 1959-04-18 | 1959-04-18 | Process for the preparation of basic substituted 4-amino-6-hydroxypyrimidines |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1122533B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003076414A2 (en) * | 2002-03-13 | 2003-09-18 | Euro-Celtique S.A. | Aryl substituted pyrimidines and the use thereof |
| US6943173B2 (en) * | 2000-07-18 | 2005-09-13 | Neurogen Corporation | 5-substituted 2-aryl-4-pyrimidinones |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE671787C (en) * | 1936-05-15 | 1939-02-15 | I G Farbenindustrie Akt Ges | Process for the preparation of pyrimidine compounds |
-
1959
- 1959-04-18 DE DEK37507A patent/DE1122533B/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE671787C (en) * | 1936-05-15 | 1939-02-15 | I G Farbenindustrie Akt Ges | Process for the preparation of pyrimidine compounds |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6943173B2 (en) * | 2000-07-18 | 2005-09-13 | Neurogen Corporation | 5-substituted 2-aryl-4-pyrimidinones |
| US7169790B2 (en) | 2000-07-18 | 2007-01-30 | Neurogen Corporation | 5-substituted 2-aryl-4-pyrimidinones |
| WO2003076414A2 (en) * | 2002-03-13 | 2003-09-18 | Euro-Celtique S.A. | Aryl substituted pyrimidines and the use thereof |
| WO2003076414A3 (en) * | 2002-03-13 | 2003-12-24 | Euro Celtique Sa | Aryl substituted pyrimidines and the use thereof |
| US7229993B2 (en) | 2002-03-13 | 2007-06-12 | Euro-Celtique S.A. | Aryl substituted pyrimidines and the use thereof |
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