5,6-Diamino-1,3-dimethyluracils

Synthesis of annelated diazepines based on unsaturated aromatic diazepines may involve the preliminary transformation of ketones into the corresponding l,3-diaryl-2,3-dibromopropane-3-ones (chalcone dibromides). The interaction between o-PDA or some of its substituted analogues with chalcone dibromides leads to the formation of aziridine derivatives [64] (see Chap. 1). However, in the case of 4-nitro-o-PDA, either azirenoquinoxalynes 53 or benzodiazepine derivatives 54 may be obtained depending on the reaction conditions [65] (Scheme 4.15). Diazepine derivatives 56 are obtained by the condensation of chalcone dibromides 51 with 5,6-diamino-1,3-dimethyluracil 55 [66], but aziridine derivatives are not isolated in this reaction. It should be noted that compounds 54 and 56 are formed owing to cyclization of the intermediate (3-enaminoketones [65, 66, 67] and are easily isolated from the reaction mixture. 

In the cyclocondensation, in the second diamine group of 1,2-diamine both the ortho and ipso heterocycle atoms may react. Such a nontrivial result was obtained while studying the interaction of chalcones 157 and cyclic unsaturated ketones 161 with 5,6-diamino- 1,3-dimethyluracil 55 [61, 62]. This refuted the data [57] on the oxazepine 158 structure of the products of this reaction the formation of the spiro systems 159 and 162 was unambiguously proven... 

An interesting pyrazine ring formation was detected between 5,6-diamino-1,3-dimethyluracil (309) and 6-hydroxy-6-(2,3,5-tri-0-benzoyl-/ -D-ribofuranosyl)-2//-pyran-3(6//)-one (310) leading to a mixture of l,3-dimethyl-7-(2,3,5-tri-0-benzoyl-/ -D-ribofuranosyl)lumazine (311), 1,3-dimethyl-6-[3-(2,3,5-tri-0-benzoyl-/ -D-ribofuranosyl)-3-oxopropyl]-lumazine (312), and 6,8-dimethyl-l-(2,3,5-tri-0-behzoyl-/ -D-ribofuranosyl)pyrrolo[l,2-/]pteridine-7,9-dione (313) (Equation (14)) <89JOC3927>. 

Reaction of 5,6-diamino-1,3-dimethyluracil with the 6-hydroxy-6- -o-ribofuranosyl-2f/-pyran-3(6//)-one 606 in toluene gave, in addition to another product (Section XI,Y), the lumazin-7-yl C-nucleoside (609) in low yield (5%) and the lumazin-7-yl homo C-nucleoside (614,16%) according to the mechanisms shown in Scheme 162. When the reaction was performed in ethylene glycol, the C-nucleoside (609) was obtained as the main product (35%) and the homo C-nucleoside (614) in 13% yield (89JOC3927). 

A/,N -Ditosyl-2,3-naphthalenediamine was reacted with succinoyl chloride in the presence of sodium carbonate to yield the napthodiazocine 75 (84MI1). Thompson reacted 5,6-diamino-1,3-dimethyluracil hydrate with succinic and phthalic anhydrides and obtained 76 and 77, respectively. When succinic anhydride was reacted with 2,3-diaminopyridine, however, only one amino group reacted to give an intermediate diamino acid, which cyclized to 22 (see Section II,A,2) (86JHC1545). Siemion and Wieland condensed homoanthranilic acid derivative 78 with 1-proline p-nitrophenyl ester and... 

Folate analogues continue to have importance in chemotherapy, especially heterocyclic analogues other than pteridines which are covered in Chapters 10.15-10.17 and 10.19. 1,3-Dimethyllumazine analogues of folates for use as model compounds have been prepared by side-chain elaboration of 6-bromomethyl-l,3-dimethyllumazine (Scheme 34) <1996JHC341>. More notable in this work, however, was the synthesis of the bromomethyl precursor itself in addition to routine bromination of the 6-methyllumazine 175 prepared by condensation of dihydroxyacetone with 5,6-diamino-l,3-dimethyluracil, a cycloaddition reaction between trimethylsilyl enol ethers and the pyrimidyl bisimine 177, via cycloadducts such as 176, afforded substituted pteridines in moderate to good yields. 

Another interesting reaction of diamines with isothiocyanates is the formation of l,3,5-triazepine-2-thione derivatives by the action of various classes of diamines on 2,3,4,5,6-penta-O-acetyl-D-gluconyl isothiocyanate (32). The reaction has been performed in acetonitrile or N,N-dimethyl-formamide solution with o-phenylenediamine, diaminomalononitrile, 5,6-diamino-l,3-dimethyluracil, 4,5-diamino-2,6-dithiopyrimidine, 4,5-diamino-2-thiopyrimidine, and 4,5-diaminopyrimidine, and afforded... 

In addition to the pyrazino[2,3-d]pyrimidin-7-yl C-nucleoside 609 and its homo analog 614, which were obtained by the reaction of 5,6-diamino-l,3-dimethyluracil with the 6-hydroxy-6-/8-D-ribofuranosyl-2/7-pyran-3(6//)-one derivative 606 (Section XI,B Scheme 162), the pyrrolo-pyrazino-pyrimidine C-nucleoside 680 was produced in 30% yield according to the mechanism outlined in Scheme 175 (89JOC3927). 

A variant of the previous reaction was utilized for the synthesis of the l,3-dimethyl-8(/3-D-ribofuranosyl)xanthosine 515 the ethyl 2,5-anhydro-o-allonodithioate derivative 512 was cyclocondensed with 5,6-diamino-l,3-dimethyluracil (513) followed by removal of the 0-protective group of 514 (86MI4) (Scheme 138). 

The 7-(alditol-l-yl)-l,3-dimethylpteridine-2,4-diones 671 were the only products obtained from the reaction of aldehydo-sugar acetates (180) with 5,6-diamino-l,3-dimethyluracil (669) followed by oxidative cyclization of... 

Diamino-l,3-dimethyluracil hydrate (5,6-diamino-l,3-dimethyl-2-pyrimidme-2,4-dione hydrate)... 

Keywords 5,6-Diamino-l,3-dimethyluracils, aryl/cycloaryl/heteroaryl aldehydes, N-bromosuccinimide (NBS), 2,2 -azoisobutyronitrile (AIBN), aqueous acetonitrile, room temperature, condensation, ring closure, 8-substituted xanthines... 

Diamino-l,3-dimethyluracil stirred 2 hrs. under Ng at 150-160° with n-butyl phenylboronate in anhydrous xylene with azeotropic distillation of the resulting n-butanol -> 7,8-dihydro-8-phenylboratheophylline. Y 89%. F. e. s. R. Caujolle and Dang-Quoc-Quan, C. r. 271 (C), 754 (1970). 

The n.m.r. spectra and rates of periodate oxidation of anomeric l-A -o-gluco-pyranosylnicotinamide cations have been measured, and they indicate that the anti-anomeric effect stabilizes the conformations in which the aglycone is equatorially oriented. The conformations of jV-hexopyranosylimidazoles are discussed in Chapter 23. Modified nucleoside derivatives [e.g. (156)] have been synthesized by condensation of 2,3,4,6-tetra-O-acetyl-jS-D-glucopyranosyl isothiocyanate with either 5,6-diamino-l,3-dimethyluracil or o-phenylenediamine. ... 

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