DE940831C - Process for the preparation of a pyridopyrimidinedione - Google Patents
Process for the preparation of a pyridopyrimidinedioneInfo
- Publication number
- DE940831C DE940831C DEH19769A DEH0019769A DE940831C DE 940831 C DE940831 C DE 940831C DE H19769 A DEH19769 A DE H19769A DE H0019769 A DEH0019769 A DE H0019769A DE 940831 C DE940831 C DE 940831C
- Authority
- DE
- Germany
- Prior art keywords
- aminopyridine
- pyrido
- dialkyl
- dione
- phenyl
- 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.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 6
- BJLUORNGPCXNHM-UHFFFAOYSA-N 1h-pyrido[3,2-d]pyrimidine-2,4-dione Chemical compound C1=CN=C2C(=O)NC(=O)NC2=C1 BJLUORNGPCXNHM-UHFFFAOYSA-N 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 4
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 14
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 5
- 235000019441 ethanol Nutrition 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 239000007859 condensation product Substances 0.000 claims description 2
- 238000006482 condensation reaction Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims 1
- 238000009833 condensation Methods 0.000 claims 1
- 230000005494 condensation Effects 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- JWDYCNIAQWPBHD-UHFFFAOYSA-N 1-(2-methylphenyl)glycerol Chemical compound CC1=CC=CC=C1OCC(O)CO JWDYCNIAQWPBHD-UHFFFAOYSA-N 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000003947 ethylamines Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- -1 3-phenyl-2-pyrido [i Chemical compound 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 229960003861 mephenesin Drugs 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000003170 musculotropic effect Effects 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 210000001032 spinal nerve Anatomy 0.000 description 1
- 238000005406 washing Methods 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Verfahren zur Herstellung eines Pyridopyrimidindions Aus »Berichte der deutschen chemischen Gesellschaft;, Bd. 57, .[192q.], S. 1168 bis 1172, war es bekannt, 3-Alkyl-2-pyrido[i, 2-a]pyrimidin-2, 4.(3H)-dione durch Umsetzung von 2-Aminopyridin mit Alkylmalonsäure-dialkylester herzustellen.Process for the preparation of a pyridopyrimidinedione From »Reports der Deutschenchemischen Gesellschaft ;, Vol. 57,. [192q.], pp. 1168 to 1172 it is known to produce 3-alkyl-2-pyrido [i, 2-a] pyrimidine-2, 4. (3H) -diones by reacting To prepare 2-aminopyridine with dialkyl alkylmalonate.
Es würde nun gefunden, daB ein neues Pyridopyrimidindion, nämlich das 3-Phenyl-2-pyridö[i, 2-a]-pyrimidin-2, 4(3H)-dion, und dessen Salze mit Basen eine ausgezeichnete depressorische Wirkung auf die unteren Spinalnervenzentren ausüben, die die vorbekannten Verbindungen nicht aufweisen. Zufolge dieser Wirkung, die der chemotherapeutischen Wir: kung des unter dem Handelsnamen Mephenesin bekannten 3-o-Tolyloxy-i, 2-propandiols ähnlich ist; lassen sich diese Pyridopyrimidindione und deren Salze therapeutisch, z. B. als muskulotrope Spasmolytika in der Behandlung von spastischen und neuromuskulären Störungen, verwenden. Das freie 3-Phenyl-2-pyrido [i, 2-a]pyrimidin-2, 4(3H)-dion besitzt, in der Ketoform dargestellt, ,folgende Formel: Das erfindungsgemäße Verfahren zur Herstellung der obengenannten Verbindungen ist dadurch gekennzeichnet, daß man einen a-Phenyhnalonsäuredialkylester mit 2-Aminopyridin erwärmt, worauf das gebildete 3-Phenyl-2-pyrido[i, 2-a]pyrimidin-2, 4(3 H)-dion gegebenenfalls mit Basen, z. B. Natriumhydroxyd, Tetramethylammoniumhydroxyd, Äthylamin und ähnlichen anorganischen und organischen Basen, umgesetzt wird. Zweckmäßig werden der a-Phenylmalonsäure-dialkylester und das z-Aminopyridin miteinander irr einem inerten organischen Lösungsmittel, z. B. Diphenyläther, zur- Reaktion gebracht. Eine bevorzugte Ausführungsform der Erfindung besteht darin, daß eine Mischung von a-Phenylmalonsäurediäthylester, 2-Aminopyridin und Diphenyläther so erwärmt wird, daß der während der Kondensationsreaktion gebildete Äthylalkohol fortwährend abdestilliert, worauf das Kondensationsprodukt von der Reaktionsmischung -abgetrennt wird. Beispiel i In einem mit Rückflußkühler versehenen Kolben werden 189 g a-Phenylmalonsäure-diäthylester und 75 g 2-Aminopyridin in einem Ölbad auf- ungefähr 16o bis 175° erhitzt. Der obere Teil des Rückflußkühlers ist mit einer Vakuumpumpe verbunden. Während der Heizperiode wird ein Druck von ungefähr 5o bis 6o mm Quecksilbersäule aufrechterhalten. Sobald die Reaktion beginnt, wird Äthylalkohol frei; die Temperatur des Rückflußkühlers wird so eingestellt, daß der Alkohol entweicht, während unverändertes Ausgangsmaterial zurückgehalten wird und in den Kolben zurückfließt. Es bildet sich allmählich ein fester gelber Körper. Nach 21/z Stunden läßt man die Reaktionsmischung abkühlen. Nach dem Erkalten wird der Inhalt des Kolbens mit Äther digeriert und filtriert. -Auf dem Filter bleibt 3-Phenyl-2-pyrido-[z, 2-a]pyrimidin-2, 4(3 H)-dion zurück. Das Produkt ist gelb und schmilzt bei ungefähr 295 bis 297° unter Zersetzung.It has now been found that a new pyridopyrimidinedione, namely 3-phenyl-2-pyrido [i, 2-a] -pyrimidin-2,4 (3H) -dione, and its salts with bases have an excellent depressive effect on the lower Exercise spinal nerve centers that do not have the previously known connections. As a result of this effect, which is similar to the chemotherapeutic effect of the 3-o-tolyloxy-1,2-propanediol known under the trade name Mephenesin; these pyridopyrimidinediones and their salts can be used therapeutically, e.g. B. as musculotropic antispasmodics in the treatment of spastic and neuromuscular disorders. The free 3-phenyl-2-pyrido [i, 2-a] pyrimidine-2, 4 (3H) -dione, shown in the keto form, has the following formula: The process according to the invention for the preparation of the above-mentioned compounds is characterized in that an α-phenylhnalonic acid dialkyl ester is heated with 2-aminopyridine, whereupon the 3-phenyl-2-pyrido [i, 2-a] pyrimidine-2, 4 (3 H) formed -dione optionally with bases, e.g. B. sodium hydroxide, tetramethylammonium hydroxide, ethylamine and similar inorganic and organic bases, is implemented. The a-phenylmalonic acid dialkyl ester and the z-aminopyridine are expediently mixed with one another in an inert organic solvent, e.g. B. Diphenyl ether brought to the reaction. A preferred embodiment of the invention is that a mixture of a-phenylmalonic acid diethyl ester, 2-aminopyridine and diphenyl ether is heated so that the ethyl alcohol formed during the condensation reaction is continuously distilled off, whereupon the condensation product is separated from the reaction mixture. EXAMPLE i 189 g of a-phenylmalonic acid diethyl ester and 75 g of 2-aminopyridine are heated in an oil bath to approximately 160 ° to 175 ° in a flask equipped with a reflux condenser. The upper part of the reflux condenser is connected to a vacuum pump. A pressure of about 50 to 60 mm of mercury is maintained during the heating season. As soon as the reaction starts, ethyl alcohol is released; the temperature of the reflux condenser is adjusted so that the alcohol escapes while unchanged starting material is retained and flows back into the flask. A solid yellow body gradually forms. After 21/2 hours, the reaction mixture is allowed to cool. After cooling, the contents of the flask are digested with ether and filtered. - 3-Phenyl-2-pyrido- [z, 2-a] pyrimidine-2, 4 (3 H) -dione remains on the filter. The product is yellow and melts at approximately 295 to 297 ° with decomposition.
Zwecks weiterer Reinigung werden io g des 3-Phenyl-2-pyrido[i, 2-a]pyrnnidm-2, 4(3H)-dions in einer heißen Mischung von 85 ccm Essigsäure und 5 ccm Wasser gelöst. Beim Stehen scheidet sich das reine Produkt =in Form glänzender- gelber Kristalle aus. Letztere werden abfiltriert und getrocknet. Das so erhaltene 3-Phenyl-2-pyrido[i, 2-a]pyrimidin-2, 4(3H)-dion schmilzt bei ungefähr 295 bis 297° unter ZersetZung.For further purification, 10 g of 3-phenyl-2-pyrido [i, 2-a] pyrnnidm-2, 4 (3H) -dione dissolved in a hot mixture of 85 cc acetic acid and 5 cc water. When standing, the pure product separates = in the form of shiny yellow crystals the end. The latter are filtered off and dried. The 3-phenyl-2-pyrido [i, 2-a] pyrimidine-2,4 (3H) -dione melts at about 295 to 297 ° with decomposition.
Zur Gewinnung der Salze geht man zweckmäßig wie _ folgt vor: Natriumsalz: Eine wäßrige Suspension von 3-Phenyl-2-pyrido-[i, 2-a]-pyrirnidin-2, 4(3H)-dion wird unter starkem Rühren mit 5o°/oiger Natronlauge langsam versetzt bis vollständige Lösung eingetreten ist. Die entstandene Lösung wird mit dem dreifachen Volumen Aceton verdünnt. Beim Stehen kristallisiert das Natriumsalz aus. Es wird abfiltriert, mit Aceton gewaschen- und getrocknet. Das Natriumsalz ist in Wasser gut löslich.To obtain the salts, it is advisable to proceed as follows: Sodium salt: An aqueous suspension of 3-phenyl-2-pyrido- [i, 2-a] -pyrirnidin-2,4 (3H) -dione 50% sodium hydroxide solution is slowly added with vigorous stirring until it is complete Solution has occurred. The resulting solution is three times the volume of acetone diluted. The sodium salt crystallizes out on standing. It is filtered off with Acetone washed and dried. The sodium salt is readily soluble in water.
Äthylaminsalz: Eine 2o°/oige wäßrige Äthylaminlösung wird langsam unter Rühren so lange in eine wäßrige Suspension von 3-Phenyl-2-pyrido[i, 2-a]-pyrimidin-2, 4(3H)-dion gegeben, bis sich eine klare Lösung gebildet hat. Dann setzt man noch ungefähr 4 Teile Aceton zu. Beim Stehen kristallisiert das Äthylaminsalz aus. Es wird abfiltriert, mit Aceton gewaschen und getrocknet, Beispiel z Eine Mischung von 9,4g a-Phenylmalonsäurediäthylester, 3,8 g 2-Aminopyridin und 25 ccm Diphenyläther wird unter Rühren während 45 Minuten auf ungefähr 185 bis igo° erwärmt. Es bilden sich allmählich gelbe Kristalle. Nach dem Abkühlen wird das gebildete 3-Phenyl-2-pyrido[i, 2-a]pyrimidin-2, 4 (3 H)-dion abgesaugt. Nach dem Waschen mit Alkohol und Äther schmilzt es bei ungefähr 295 bis 297° unter Zersetzung.Ethylamine salt: A 20% aqueous ethylamine solution is slow while stirring so long in an aqueous suspension of 3-phenyl-2-pyrido [i, 2-a] -pyrimidine-2, 4 (3H) -dione added until a clear solution has formed. Then you still bet about 4 parts of acetone to it. The ethylamine salt crystallizes out on standing. It is filtered off, washed with acetone and dried, Example z A mixture of 9.4 g of a-phenylmalonic acid diethyl ester, 3.8 g of 2-aminopyridine and 25 cc of diphenyl ether is heated to about 185 to igo ° for 45 minutes while stirring. Make it up yellow crystals gradually appear. After cooling, the 3-phenyl-2-pyrido [i, 2-a] pyrimidine-2, 4 (3 H) -dione sucked off. After washing with alcohol and ether it melts at about 295 to 297 ° with decomposition.
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US940831XA | 1953-04-24 | 1953-04-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE940831C true DE940831C (en) | 1956-03-29 |
Family
ID=22242775
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEH19769A Expired DE940831C (en) | 1953-04-24 | 1954-03-26 | Process for the preparation of a pyridopyrimidinedione |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE940831C (en) |
-
1954
- 1954-03-26 DE DEH19769A patent/DE940831C/en not_active Expired
Non-Patent Citations (1)
| Title |
|---|
| None * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2902438C2 (en) | ||
| DE1620694B2 (en) | Process for the preparation of 5-methyl-7-diethylamino-s-triazolo [1,5-a] pyrimidine and its salts with acids | |
| DE940831C (en) | Process for the preparation of a pyridopyrimidinedione | |
| DE3872956T2 (en) | METHOD FOR PRODUCING 2,4-DIAMINO-6- (1-PIPERIDINYL) -PYRAMIDIN-N-OXIDE. | |
| DE2855279C2 (en) | Chelated 1,8-naphthyridine derivative, process for its preparation and process for preparing 1,8-naphthyridine derivatives | |
| EP0115295B1 (en) | Process for the preparation of riboflavine | |
| DE681523C (en) | Process for the preparation of quaternary ammonium compounds | |
| AT233010B (en) | Process for the preparation of new benzo-dihydro-1, 2, 4-thiadiazine-1, 1-dioxyden | |
| DE897103C (en) | Process for the preparation of 2-diphenylacetyl-1, 3-indanedione and its non-toxic metal salts | |
| DE960813C (en) | Process for the production of unsaturated ª † and ª € lactones | |
| DE901053C (en) | Process for the production of guanidine thiocyanate | |
| DE442655C (en) | Process for the preparation of cyclohexenylalkylbarbituric acids | |
| DE894994C (en) | Process for the production of aliphatic mercury ketone compounds | |
| DE719830C (en) | Process for the production of salts of higher molecular phosphatidic acids | |
| DE698546C (en) | Process for producing an amidine | |
| DE404175C (en) | Process for the preparation of sulfocyanine compounds | |
| DE2422430C3 (en) | Derivatives of secalonic acid D, process for their preparation and their use in combating tumors | |
| DE906334C (en) | Process for the preparation of quinolinium compounds | |
| AT319960B (en) | Process for the preparation of new pyridazine compounds | |
| DE881039C (en) | Process for the preparation of the pentaerythritol dichlorohydrin monosulfuric acid ester | |
| DE611054C (en) | Process for the preparation of paradiketocamphane carboxylic acid and of ketooxycamphane carboxylic acid | |
| AT315175B (en) | Process for the production of 2-pyridylthioacetamide and its salts | |
| DE1768787C3 (en) | (o-Carboxy-phenyl) -acetamidine, process for their preparation and (o-CarboxyphenyO-acetamidine-containing preparations | |
| DE488605C (en) | Process for the preparation of tetranitrodianthrone | |
| DE721930C (en) | Process for the production of 8,9-Dioxypyrimidinopyrazinen (8,9-Dioxyazinpurinen, Leukopterin and its Abkoemmlingen) |