1.4.6- Triaminopyrimidine-2 -ones

The reaction of 6-amino-5-(l,2-diethoxycarbonylhydrazino)pyrimidines with enamines represents another convenient method for the preparation of pteridines. Fusion of 5-(l,2-diethoxycarbonylhydrazino)-2,4,6-triaminopyrimidine (281) with an excess of mor-pholinocyclohexene leads to 2,4-diaminotetrahydrobenzo[g]pteridine, and with the morpholinoenamine (282) from 17/3-hydroxy-5a-androstan-3-one regioselective condensation to the fused pteridine (283) takes place in almost quantitative yield (equation 101) (71CC83). 6-Amino-5-nitroso- and 6-amino-5-phenylazo-pyrimidines react similarly, imitating the Timmis-type reaction (72CPB1428). 

The reaction involves an electrophilic attack into the 5-position of the pyrimidine ring and thus only those pyrimidines that are activated toward electrophilic substitution by the presence of electron-donating substituents at the 2- and 4-positions undergo cyclization. 2,4,6-Triaminopyrimidine, 6-aminouracil, 6-amino-2-thiouracil, 4-amino-2,4 dimercaptopyrimidine, 2,4-diaminopyrimidin-6(l/I)-one, and various 4-amino-vV-alkyl and aryl pyriinidones have all been converted into pyrido[2,3-[Pg.160]

Triaminopyrimidin-6(l/0-one 39 reacts with a range of fluorocarbonyls to give fluoropterins (Scheme 6). The fluoropterins are even more insoluble than the parent compounds and are also stable to nucleophiles and bases in dilute aqueous solution <96113017 >. 

Several studies deal with the reactivity of 2,4-disubstituted-6-aminopyrimidines, which have competing sites for ring formation with 1,3-biselectrophiles. Treatment of 2,4,6-triaminopyrimidine with ethyl acetoacetate in acetic acid formed the pyrimido[l,6-tf]pyrimidin-4-one 216, while the expected pyrido[2,3-r/]pyrimidin-7-one 217 was obtained under thermal conditions (Scheme 34) <1999JOC634>. 

The triaminopyrimidine 466 was also reacted with ethyl acetoacetate in Ph20 or dioxane under thermal conditions to form the diamino-5-methylpyrido[2,3- pyri idin-7(8//)-one 483 <1999JOC634>. Its reaction with bromo(nitro)-malonaldehyde in boiling EtOH in the presence of HCl afforded the corresponding 6-bromo(nitro) analogues 484 and 485, respectively <1996JME1438, 1997JME470>. 

The thermal cyclization reaction of 2,4,6-triaminopyrimidine 466 with ethyl 2-cyclohexanonecarboxylate 588 in PhgO at 190 °C gave the tetrahydropyrimido[4,5-r-]isoquinolin-6(5//)-one 589 as the sole product (Equation 48) <1999JOC634>. 

Formation of l,2,4-triazolo[l,5-c]pyrimidine-5(6//)-thiones or their 5(6//)-ones by the reaction of l,4,6-triaminopyrimidine-2(l//)-thiones (468) with the Vilsmeier reagent has been found to be dependent on the temperature. Thus, treatment of 468 with phosphoryl chloride and DMF at 0-5°C afforded mainly the thiadiazolopyrimidinium chloride 470 in addition to the thione 471, but at 25°C a mixture of 471 and 7-formamido-l,2,... 

In recent years, a considerable amount of attention has been focussed on the derivatization of the pyrimidine core structure on resins. Usually, the sequential substitution of the pyrimidine template on a resin with various amines provides a diverse set of 2,4,6-triaminopyrimidines. Synthetic strategies leading to pyrimidines with one [136], two [137,138], and three diversity points have been reported [139-141]. 

I,4,6 Triaminopyrimidine-2-thione reacts with the Vilsmeier reagent to give one or more of several products according to the temperature of the reaction. In this way, thiadiazolopyrimidines are formed at 0 C. 

An unusual formyl ketone equivalent which has been used for the synthesis of biopterin (10, X = H) via the actyl derivative 10 (X = Ac) is the phenylhydrazone of 5-deoxy-L-ribose (9) which has been condensed with 2,5,6-triaminopyrimidin-4(3/7)-one.78... 

A readily available formyl ester equivalent is ethyl dibromo- or dichloroacetate, or the free acid. For example xanthopterin, 2-aminopteridine-4,6(3/T,5/T)-dione, can be made in 65% yield via the intermediate dibromoacetamino compound, from 2,5,6-triaminopyrimidin-4(3//)-one and dibromoacetic acid.82... 

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