7-Alkyl purine-2,4- -diones

Ultraviolet (UV) spectroscopy does not tend to be the method of choice for structure determination, but a list of UV absorptions was given in the review by Knowles <1996CHEC-II(7)489>. Fluorescence properties and triplet yields of [l,2,3]triazolo[4,5-r/ pyridazines in various solvents have been reported <2002JPH83>. These heterocyclic systems were found to be photochemically very stable. In a recent paper, Wierzchowski et al. studied the fluorescence emission properties of 8-azaxanthine ([l,2,3]triazolo[4,5-r/ pyrimidine-5,7-dione) and its A -alkyl derivatives at various pH s <2006JPH276>. For the 8-azaxanthines, an important characteristic of emission spectra in aqueous solutions was the unusually large Stokes shift. Since 8-azaxanthine is a substrate for purine nucleoside phosphorylase II from Escherichia coli, the reaction is now monitored fluorimetrically. The fluorescence properties of [l,2,3]triazolo[4,5-r/ -pyrimidine ribonucleosides were earlier described by Seela et al. <2005HCA751>. 

In addition to the intermolecular alkylation reactions described, intramolecular alkylations have been reported. One example is the intramolecular reaction of 7-(3-chloropropyl)theophylline to give l,3-dimethyl-7,8-dihydro-6//-pyrrolo[2,l-/]purine-2,4(l/f,3/f)-dione (27). ... 

An alternate method started from 5,6-diamino-1,3-dipropyluracil which reacted with 4-chlorobutyryl chloride to give 6-amino-5-(4-chlorobutyryl)amino-1,3-dipropyl- I //,3//-pyrimidine-2,4-dione (17a) and subsequently underwent cyclization in diphenyl ether under reflux. The water produced in this step hydrolyzed the product into 8-(3-hydroxypropyl)-l,3-dipropyl-7/7-purine-2,4(1/7,3/7)-dione (19a). Heating the latter in thionyl chloride led to the appropriate 8-(3-chloropropyl) derivative 19b which underwent intramolecular alkylation with NaOCH3 to afford the final tricyclic 20b. Another route started from 6-amino-5-(4-chlorobutyl)amino derivative 17a by an intramolecular alkylation to 6-amino-5-(2-oxopyrolidin-l-yl)-1,3-dipropyl- 1/7,3/7-pyrimidine-2,4-dione (17b) and its subsequent cyclization by phosphorus oxychloride under reflux to 20b (94JHC81) (Scheme 5). 

Bromation of l,3-dimethyl-7-phenyl-oxazolo[2,3-/]-purine-2,4-dione 49 (bromine in acetic acid), took place at position 6 (compound 50). Nitration with potassium nitrate in sulfuric acid did not take place at Cg but instead gave 7-(4-nitrophenyl)-oxazolo[2,3-/]purinedione derivate 51 due of the protonation of the oxazolo-purine ring system by acid. Alkylation at position 1 with ethyl iodoacetate in dimethylformamide in the presence of potassium carbonate gave 52 (90KGS1396) (Scheme 14). 

The third method utilized 8-bromo-7-(2-chloroethyl)purine-2,4-dione 109 obtained by alkylation of the sodium salt of 8-bromopurinedione with 1-bromo-2-chloroethane, followed by cyclization with sodium sulfide producing 1,3-di-alkyl-6,7-dihydrothiazolo-[2,3 / ]purine-2,4(l //,3//)-diones 110 (96KFZ(3)49)... 

Three methods were reported to obtain the title compounds. The first was based on a reaction sequence starting from 5,6-diamino-4-thiouracil-sodium salt, alkylation with 1,2-dibromoethane to 7,8-diamino-2,3-dihydro-5//-thiazolo-[3,2-c]pyrimidine (135) and fusion with urea or thiourea under formation of a third ring to the respective 7,8-dihydrothiazolo[2,3-/]purine-2,5(l//,3//)-dione (136) and 2,3,7,8-tetrahydro-2-thioxothiazolo[2,3- ]purin-5(l//)-one (137) (92FES1315) (Scheme 37). 

The following examples illustrate the scope of this reaction 3-aminopyr-role-2-carboxamide to a pyrrolo[3,2-d]pyrimidine-2,4-dione205 2-amino(IV-alkyl)benzamides to 3-alkyl-2,4-quinazoline-2,4-diones266 5-aminothiazole-4-carboxamide to thiazolo[5,4-d]pyrimidine-2,4-dione (see 149)236 4-aminoimidazole-5-carboxamide (and derivatives) to purine-2,6-diones (see... 

H-Purin-2,6-dione, 1,7-dihydro- xanthine H H 6H-Purin-2,6-dione, 1,7-dihydro-, Cs-alkyl- 1587, 4249 2539, 2939 ... 

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