4-Amino-2-pyrimidone

Cytidine 4-Amino-2-pyrimidone Uridine 2,6-Pyrimidinedione Thymidine 5-Methyl-2,6-pyrimidinedione (5-methyluracil)... 

Figure 5.9 Fixed (35, 36) and mobile (34) tautomers of some 4-amino-2-pyrimidones.

A product (180), of unexpected structure, was also obtained by treatment of the Michael adduct (179) of the amino-pyrimidone (178) and ethyl propiolate with acid. ... 

Flucytosine. Flucytosine (17) or 5-fluorocytosine (4-amino-5-fluoro-2-pyrimidone, 5-FC), C H FN O, is a pyrimidine derivative, that is efficient against Candida albicans Cryptococcus neoformans and Torulopsis glabrata. 

A. Mononucleotides.—A new journal has appeared in the past year consisting of abstracts of papers published in the nucleotide and nucleic acid fields. The use of nucleosides and nucleotides as potential therapeutic agents has been reviewed. Nucleotides which have been prepared recently using conventional methods of phosphorylation include those derived from 6-methylthiopurine ribonucleoside (la), 5-methylsulphonyluridine (lb), l-(jS-D-ribofuranosyl)-2-pyrimidone (Ic), 3-(jS-D-ribofuranosyl)-4-pyrimidone (Id), and various thionucleosides. - O-Phosphorylated 3 -amino-3 -deoxythymidine (2a) and 5 -amino-5 -deoxythymidine (2b)... 

Aminopyrimidines have been studied by Albert et al. (1948), and, by relying on the pAj-values at 20° of aminopyridines, there is no doubt that the 4-amino-derivative is protonated on the ring nitrogen N-1 (pAj = 5 69, as compared with pA = 1-23 for unsubstituted pyrimidine). The 2-amino-derivative is a weaker base (pAg = 3 45) and the 5-amino-derivative is weaker still (p/Cg = 2-60). An interesting ultraviolet spectral correlation has recently been pointed out (Albert and Taguchi, 1973) between compounds containing the 2-aminopyrimidinium and 2-pyrimidone structures ([59] and [60]). 

A similar route to the i -triazolo[4,5-d]pyrimidine ( 8-azapurine ) ring system has been developed. This involves reaction of 4-amino-l,2,3-triazole-5-carboxamide or its ring iV-alkyl derivatives with formamide (Scheme 46). - 232-234 pyrimidone derivatives thus... 

In a similar vein, the displacement of the nitrated amino group in pyrimidone (61-2), prepared in the same way as (60-5) using the methoxyl pyridinealdehyde, with the ranitidine nucleus (61-1) affords the H2 blocker donetidine (61-4) [63] after cleavage of the methyl ether. 

Quaternary salts having structure 51 have been isolated R, and R2 are amino, alkoxy, and thioalkoxy substituents. Except in the case of 2-amino products, dealkylation to give a 2-pyrimidone takes place readily under alkaline conditions.158... 

Amino-l-methylimidazole (169) reacted with DMAD145 in dioxane to form 30% of imidazo[l,2-a]pyrimidone (170), identified by the low-field 3-proton, and 5% of the diazepine 171, which was presumably built up by cyclobutene formation across the 4,5-double bond of 169 and ring expansion.148 Both l-methyl-2-methylthioimidazoline and its... 

Triamino-4-pyrimidone (211) and 2,4,5,6-tetraminopyrimidine (212) add DMAD and DEAD to give the isoxanthopterin-6-acetates and their 4-amino analogs (213)339 via Michael reactions starting with the most basic (5-)amino groups. 

Similar condensations of 5-amino-6-substituted anilino-3-methyluracils with glyoxal, diacetyl and benzil led to the corresponding 3-methyl-8-substituted phenyllumazines of which the 8-(4-chlorophenyl)- and 8-(3,5-dimethylphenyl)-3-methyllumazines showed activity against cultured Plasmodium falciparum <90AJC1449>. 5-Amino-6-methylamino- and 6-/Miydroxyethyl-2-methylthio-4(3//)pyrimidone also condense with glyoxal, diacetyl, and benzil to the corresponding 8-substituted... 

Condensation with ethyl formate (HC02Et) and cyclization with guanidine gives the pyrimidine ring system but with an OH instead of the required amino group. Aromatic nucleophilic substitution in the pyrimidone style from Chapter 43 gives trimethoprim. 

Similarly, reaction of anti-amino ketoximes with phosgene results in the formation of intermediate 2-pyrimidone Ai-oxide derivatives [785] ... 

Each of the diazines can be constructed from an appropriate source of two nitrogens and a dicarbonyl compound. In the case of pyridazines, the nitrogen source is, of course, hydrazine and this in combination with 1,4-dicarbonyl compounds readily produces dihydro-pyridazines, which are very easily dehydrogenated to the aromatic heterocycle. Pyrimidines result from the interaction of a 1,3-dicarbonyl component and an amidine (as shown) or a urea (giving 2-pyrimidones) or a guanidine (giving 2-amino-pyrimidines), without the requirement for an oxidation step. 

The reaction involves an electrophilic attack into the 5-position of the pyrimidine ring and thus only those pyrimidines that are activated toward electrophilic substitution40 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( iff )-one, and various 4-amino-AT-alkyl and aryl pyrimidones have all been converted into pyrido[2,3-d]pyrimidines when treated with the required 40 B, Lythgoe, A. R. Todd, and A. Topham, J. Otem.Soc. p. 316 (1944). 

For a related cyclization of 2-(eyanoamino)nicotinonitriles with hydrogen halides to give the corresponding 4-amino-2-halopyrido[2,3-t/]pyrimidones, see refs 549 and 550. 

Other synthons for 1,3-dicarbonyl compounds which have been successfully applied include / -chloro-a,/ -unsaturated ketones and aldehydes,/J-amino-a,/J-unsaturated ketones, vinylamidinium salts,and propiolic acid, reaction of which with urea gives uracil directly in about 50% yield. " 1,3-Ketoesters with formamidine produce 4-pyrimidones. 2-Aminomalondialdehyde leads to 5-aminopyrimidines. In analogy, pyrimidines fused to other rings, for example as in quinazolines, can be made from ort/io-aminonitriles and in general, from (3-... 

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