DE908857C - Process for the preparation of an easily soluble compound from theophylline and 3-aminomethylpyridine - Google Patents

Process for the preparation of an easily soluble compound from theophylline and 3-aminomethylpyridine

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Publication number
DE908857C
DE908857C DEH12135A DEH0012135A DE908857C DE 908857 C DE908857 C DE 908857C DE H12135 A DEH12135 A DE H12135A DE H0012135 A DEH0012135 A DE H0012135A DE 908857 C DE908857 C DE 908857C
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Germany
Prior art keywords
theophylline
aminomethylpyridine
compound
preparation
soluble compound
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Expired
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DEH12135A
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German (de)
Inventor
Dr Phil Reinhard Schlaepfer
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F Hoffmann La Roche AG
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F Hoffmann La Roche AG
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Publication date
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Publication of DE908857C publication Critical patent/DE908857C/en
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Description

Verfahren zur Herstellung einer leicht löslichen Verbindung aus Theophyllin und 3-Aminomethylpyridin Aus den Patentschriften 214 376, 217 62o, 223 695 und 224 981 ist es bekannt, lösliche Verbindungen aus Theophyllin und Diaminoverbindungen, wie Piperazin und Äthylendiamin, herzustellen.Process for the preparation of a readily soluble compound from theophylline and 3-aminomethylpyridine It is known from patents 214 376, 217 62o, 223 695 and 224 981 to prepare soluble compounds from theophylline and diamino compounds such as piperazine and ethylenediamine.

Es wurde nun gefunden, daß Theophyllin mit 3-Aminomethylpyridin zu einer farblosen Verbindung zusammentritt. Die kristalline Verbindung aus 3 MOI Theophyllin und 2 M01 3-Aminomethylpyridin erweicht bei 155 bis 16o', zeigt jedoch im offenen Kapillarrohr keinen charakteristischen Schmelzpunkt, da sich das 3-Aminomethylpyridin beim Erhitzen verflüchtigt. Beim Eintragen in Wasser wird unterhalb pH 8 die Verbindung unter Abscheidung von Theophyllin teilweise hydrolytisch gespalten, durch Zugabe von freiem 3-Aminomethylpyridin bzw. Erhöhen des pH auf 8,3 können stabile wäßrige Lösungen hergestellt werden. Untersuchungen am isolierten überlebenden Katzenherzen zeigten, daß die erfindungsgemäße Verbindung eine gegenüber dem Theophyllin und den bekannten Theophyllinverbindungen verstärkte Coronarwirkung aufweist.It has now been found that theophylline combines with 3-aminomethylpyridine to form a colorless compound. The crystalline compound of 3 MOI theophylline and 2 M01 3-aminomethylpyridine softens at 155 to 16 °, but does not show a characteristic melting point in the open capillary tube because the 3-aminomethylpyridine evaporates on heating. When added to water below pH 8, the compound is partially hydrolytically cleaved with the separation of theophylline; stable aqueous solutions can be prepared by adding free 3-aminomethylpyridine or increasing the pH to 8.3. Investigations on the isolated surviving cat heart showed that the compound according to the invention has a stronger coronary effect than the theophylline and the known theophylline compounds.

Es lassen sich konzentrierte wäßrige Lösungen der genannten Verbindung herstellen, die sich sowohl für die orale wie auch für die parenterale Applikation eignen. Dabei erübrigt sich die Zugabe der üblichen Lösungsvermittler, die einerseits als Ballaststoffe wirken, andererseits zum Teil unerwünschte pharmakologische oder klinische Nebenreaktionen auslösen können.Concentrated aqueous solutions of the compound mentioned can be used produce that are suitable for both oral and parenteral administration suitable. There is no need to add the usual solubilizers, on the one hand act as dietary fiber, on the other hand partly undesirable pharmacological or can trigger clinical side reactions.

Beispiel i 40 Gewichtsteile kristallwasserfreies Theophylhn werden in 16o Gewichtsteilen 3-Anünomethylpyridin zweckmäßig unter leichtem Erwärmen gelöst. Beim Animpfen oder Stehen in der Kälte kristallisiert die Verbindung aus 3 Mol Theophyllin und?, M01 3-Aminomethylpyridin in Nadeln aus.Example i 40 parts by weight of anhydrous Theophylhn are dissolved in 160 parts by weight of 3-anenomethylpyridine, expediently with gentle heating. When inoculating or standing in the cold, the compound of 3 moles of theophylline and ?, M01 3-aminomethylpyridine crystallizes out in needles.

Man trennt die Verbindung unter Ausschluß von Kohlendioxyd und Luftfeuchtigkeit von der Mutterlauge ab.The compound is separated in the absence of carbon dioxide and atmospheric moisture from the mother liquor.

Anhaftende Mutterlauge kann entweder durch Stehenlassen der Verbindung auf Ton im Vakuumexsikkator über fester Kalilauge oder durch Auswaschen mit Tetralin und Nachwaschen mit Petroläther oder Äther entfernt werden.Adhering mother liquor can either be obtained by letting the compound stand on clay in a vacuum desiccator over solid potassium hydroxide solution or by washing out with tetralin and washing with petroleum ether or ether can be removed.

Mit frischem Theophyllin kann aus der Mutterlauge erneut die Verbindung erhalten werden. Die farblose Verbindung aus 3 Mol Theophyllin und 2 Mol 3-Aminomethylpyridin emeicht zwischen 155 und 16o', ohne scharf zu schmelzen; durch anhaltendes Sauge'n mittels der Wasserstrahlpumpe kann sie verwittern und in eine neue Verbindung aus 9, Mol Theophyllin und i Mol 3-Aminomethylpyridin vom Erweichungsintervall 165 bis 170' übergeführt werden.The compound can be obtained again from the mother liquor with fresh theophylline. The colorless compound of 3 moles of theophylline and 2 moles of 3-aminomethylpyridine weighs between 155 and 16o 'without melting sharply; If you keep sucking it with the water jet pump, it can weather and be converted into a new compound of 9 moles of theophylline and 1 mole of 3-aminomethylpyridine with a softening range of 165 to 170 '.

Beispiel 2 22 Gewichtsteile Theophyllin mit i Mol Kristallwasser oder eine äquivalente Menge kristall-,vasserfreien Theophyllins werden in 66,74 bzw. 68,74 Gewichtsteilen frisch ausgekochtem Wasser suspendiert und dazu 19,86 Gewichtsteile 3-Aminomethylpyridin zugesetzt. Es entsteht eine klare Lösung d22' = i,o86, 4' welche 2o 0/, wasserfreies Theophyllin enthält und sich vorzüglich für die parenterale Applikation von Theophyllin eignet.Example 2 22 parts by weight of theophylline with 1 mole of water of crystallization or an equivalent amount of crystal-free, anhydrous theophylline are suspended in 66.74 or 68.74 parts by weight of freshly boiled water and 19.86 parts by weight of 3-aminomethylpyridine are added. The result is a clear solution d22 '= 1, 086, 4' which contains 2o 0 /, anhydrous theophylline and is particularly suitable for the parenteral application of theophylline.

Claims (3)

PATENTAN,.3pRüciir,: :i. Verfahren zur Herstellung einer #wasserlöslichen Verbindung aus Theophyllin und 3-Aminomethylpyridin, dadurch gekennzeichnet, daß Theophyllin mit 3-Aminomethylpyridin umgesetzt wird. PATENTAN, .3pRüciir ,:: i. Process for the preparation of a # water-soluble Compound of theophylline and 3-aminomethylpyridine, characterized in that Theophylline is reacted with 3-aminomethylpyridine. 2. Verfahren nach Anspruch i, dadurch gekennzeichnet, daß Theophyllin mit 3-Aminomethylpyridin im Überschuß umgesetzt und die ausgeschiedene Verbindung von der Mutterlauge abgetrennt wird. 3. Verfahren nach Anspruch i, dadurch gekennzeichnet, daß man auf Theophyllin 3-Aminomethylpyridin in einer Menge von mindestens 2/, Mol in Gegenwart von Wasser einwirken läßt. 2. The method according to claim i, characterized in that theophylline is reacted with 3-aminomethylpyridine in excess and the excreted compound is separated off from the mother liquor. 3. The method according to claim i, characterized in that theophylline is allowed to act on 3-aminomethylpyridine in an amount of at least 2 /, mol in the presence of water. Angezogene Druckschriften: Deutsche Patentschriften Nr. 214 376, 217 62o, 224 981:, 223 695. Cited publications: German patent specifications No. 214 376, 217 62o, 224 981 :, 223 695.
DEH12135A 1951-05-28 1952-04-11 Process for the preparation of an easily soluble compound from theophylline and 3-aminomethylpyridine Expired DE908857C (en)

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CH908857X 1951-05-28

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DE908857C true DE908857C (en) 1954-06-08

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE223695C (en) *

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE223695C (en) *
DE217620C (en) *
DE214376C (en) *
DE224981C (en) *

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