Alfonz Rybár

[f]-Fused purine-2,6-diones: Synthesis of new [1,3,5]- and [1,3,6]-thiadiazepino-[3,2-f]-purine ring systems

Summary6-Phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,8,9-hexahydro-[1,3,5]-thiadiazepino-[3,2-f]-purine (5) was obtained by a three-step synthesis from 8-mercapto-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (1) and 2-(benzoylamino)-ethyl chloride (2)via 8-(benzoylaminoethylthio)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (3) and its chloromido derivative4. The analogous 9-phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,6,7-hexahydro-[1,3,6]-thiadiazepino-[3,2-f]-purine (7) was synthesized either from compound1 and N-(2-chloroethyl)-benzimido chloridevia N-(chloroethyl)-S-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-7H-purin-8-yl)-benzothioimide (6), or alternatively from 7-(2-benzoylaminoethyl)-8-bromo-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (9), its 8-mercapto derivative10 and the corresponding chloroimido compound11 being the intermediates.Zusammenfassung6-Phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,8,9-hexahydro-[1,3,5]-thiadiazepino-[3,2-f]-purin (5) wurde in drei Stufen aus 8-Mercapto-1,3-dimethyl-3,7-dihydro-1H-purin-2,6-dion (1) und 2-(Benzoylamino)-ethylchlorid (2)via 8-(2-Benzoylaminoethylthio)-1,3-dimethyl-3,7-dihydro-1H-purin-2,6-dion (3) und sein entsprechendes Chlorimid-Derivat4 dargestellt. Das analoge 9-Phenyl-1,3-dimethyl-2,4-dioxo-1,2,3,4,6,7-hexahydro-[1,3,6]-thiadiazepino-[3,2-f]-purin (7) wurde entweder aus Verbindung1 und N-(2-Chlorethyl)-benzimidochloridvia N-(Chlorethyl)-S-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-7H-purin-8-yl)-benzothioimid (6) oder aus 7-(2-Benzoylaminoethyl)-8-brom-1,3-dimethyl-3,7-dihydro-1H-purin-2,6-dion (9), seinem 8-Mercapto-Analogen10 und dem entsprechenden Chlorimid-Derivat11 erhalten.

7,8-Disubstituted [1,3]-thiazino-[2,3-f]-purine derivatives

Summary7-Cyanomethyl-8-ethoxycarbonylmethylthio- (3a), 7-cyanomethyl-8-cyanomethylthio- (3b) and 7-ethoxycarbonylmethyl-8-ethoxycarbonylmethylthio-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (3c) afforded 7-amino-8-ethyoxycarbonyl-(5), 7-amino-8-cyano- (6), and 8-ethoxycarbonyl-7-hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-6H-[1,3]-thiazino-[2,3-f]-purine (7), respectively, on intramolecular Claisen-type condensation.Zusammenfassung7-Cyanomethyl-8-ethoxycarbonylmethylthio- (3a), 7-Cyanomethyl-8-cyanomethylthio- (3b) und 7-Ethoxycarbonylmethyl-8-ethoxycarbonylmethylthio-1,3-dimethyl-3,7-dihydro-1H-purin-2,6-dion (3c) liefern bei einer intramolekularen Claisen-Kondensation die 7-Amino-8-ethoxy-carbonyl-(5), 7-Amino-8-cyano- (6), und 8-Ethoxycarbonyl-7-hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-6H-[1,3]-thiazino-[2,3-f]-purine (7).

New synthetic approach to 8-allyltheophylline

SummaryThe synthesis of 8-allyltheophylline (8) from 5,6-diamino-1,3-dimethyluracil (1) and 3-butenoic acid byTraubes methodvia 6-amino-5-(3-butenoylamino)-1,3-dimethyluracil (2) failed because an attempted alkaline cyclization of the intermediate2 afforded (E)-8-(1-propenyl)-theophylline (3) under rearrangement of the terminal C=C bond. Therefore, the cyclodehydratation of 6-(3-butenylamino)-5-nitroso-1,3-dimethyluracil (7), available from 6-chloro-1,3-dimethyluracil (5)via 6-(3-butenylamino) derivative6 has to be used for obtaining the required product8.Zusammenfassung8-Allyltheophyllin (8) kann nicht mittels derTraube-Synthese aus 5,6-Diamino-1,3-dimethyluracil und 3-Butensäurevia 6-Amino-5-(3-butenoylamino)-1,3-dimethyluracil (2) hergestellt werden, wei bei der alkalischen Cyclisierung des Zwischenproduktes2 Umlagerung der terminalen C=C-Doppelbindung unter Bildung von (E)-8-(1-Propenyl)theophyllin (3) erfolgt. Zur Darstellung der Verbindung8 muss man daher die Dehydratationscyclisierung von 6-(3-Butenylamino)-5-nitroso-1,3-dimethyluracil (7) anwenden. Letzteres ist aus 6-Chloro-1,3-dimethyluracil über das 6-(3-Butenylamino)-Derivat6 zugänglich.