Pyrimidine compounds

As mentioned above (Section 2.13.2.1.3), bipyrimidine photoproducts can arise, probably by reaction between two radicals. Thus, irradiation of an aqueous solution of 5-bromouracil (ill R=Br) in the absence of oxygen produces a variety of products including uracil, barbituric acid, 5-carboxyuracil (111 R = CO2H), several non-pyrimidine compounds and, as a stable end-product, the biuracil (114 R = H). A similar product (114 R = Me) is formed from 5-bromo-l,3-dimethyluracil (ilS). When two such related uracil derivatives are irradiated together, a mixed bipyrimidine product is formed, inter alia (B-76MI21302). 

Chapter 4 Compounds containing one or more nitrogen atoms in the macroring, whether or not the nitrogen is part of another heterocyclic subunit. Certain pyridine and pyrimidine compounds have been included in chapter 3 as well. 

The pyrimidine compounds are known to undergo a rearrangement of the 0-alkyl derivatives to the iV-alkyl ones. The methoxy derivatives of 1,3,5-triazine display a similar behavior. On applying methyl iodide to 2,4-dimethoxy-l,3,5-triazine one of the methyl groups is shifted giving rise to l-methyl-4-methoxy-derivative (22). This compound was also obtained by methylation of 4-methoxy-2-oxo-1,2-dihydro-1,3,5-triazine (18) with diazomethane. At higher temperature (100°C) in presence of methyl iodide a shift of both methyl groups takes place and methiodide is formed simultaneously (23). Similarly,... 

To hydrolyze the sulfa pyrimidine compound, the same is heated at 90°C with 200 cc of 2 (M potassium hydroxide solution for about one hour until complete solution is obtained. The resultant solution is then cooled to room temperature (25°C) and acidified with acetic acid to precipitate the hydrolyzed product, which is then recrystallized from dilute acetone admixed with animal charcoal. 

The Wiirtz reaction can be used to incorporate some functionality in an alkyl chain bound to tin in a stannane111, e.g. by reaction of Ph3SnCH2I or (ICH2)4Sn respectively with RSNa (where RH = benzothiazole, benzoxazole, 1-methylimidazole, pyrimidine). Compounds of the type Ph3SnCH2SR or (RSCH2)4Sn were obtained. 

It is important to note that besides these synthetic pathways a very important access to [ 1,2,4]triazolo[ 1,5 z] pyrimidine derivatives is the Dimroth rearrangement of [l,2,4]triazolo[4,3-c]pyrimidine compounds. This type of ring transformation is specifically discussed in Section 11.16.5.2 these possibilities are also reviewed in Section 11.16.7. As these isomerizations always take place into the direction of the [l,2,4]triazolo[l,5-c]pyrimidine ring, in several studies only these products are described without special (or any) note of the primarily formed [l,2,4]triazolo[4,3-c]pyrim-idine ring. Table 17 contains the stmctures of some [l,2,4]triazolopyrimidines and benzologues with a fusion site of the triazole ring that have been formed via transformation of the isomeric [ 1,2,4] triazolo[4,3-f]-pyrimidine compounds with or without isolation of these intermediates. 

Table 17 [1,2,4]Triazolopyrimidines and benzologues with a fusion site of the triazole ring that have been formed via transformation of the isomeric [1,2,4]triazolo[4,3-c]pyrimidine compounds...

Golankiewicz et al. <1995JME3558> described a synthesis of the title ring system by ring closure of the five-membered ring. In this case, the pyrimidine compound 253 was treated first with trimethylchlorosilane and, then, with hexamethyldisilazane, and as a consequence of a quite complicated rearrangement the imidazotriazine compound 254 was obtained in excellent yield (80-90%). 

Pyrimidine is a six-membered aromatic heterocyclic compound that contains two nitrogen atoms, separated by a carbon atom, in the ring. Nucleic acids, DNA and RNA, contain substituted purines and pyrimidines. Cytosine, uracil, thymine and alloxan are just a few of the biologically significant modified pyrimidine compounds, the first three being the components of the nucleic acids. 

Of the investigated 4-oxo-4/f-pyrido[l,2-a]pyrimidines, compound (63 R = H) was moderately active against solid tumors,384 whereas its 7-carboxy derivative showed a weak antiallergic activity in the PCA test.63 The blood sugar level reducing activity of 4-oxo-4tf-pyrido[l,2-a]pyrimidine-3-esters and their derivatives is about one-sixth of that of tolbutamide.136... 

Amino-5-methoxy pyrimidine is obtained having a melting point of about 300°C by condensation of methoxymalonic acid ester with guanidine carbonate in the presence of sodium ethylate. The resultant reaction product is then converted to 2-amino-5-methoxy-4,6-dichloropyrimidine (melting point 216°C to 217°C) by heating this reaction product with phosphorus oxychloride. The dichloro compound is then suspended in water with zinc dust and is tested in the presence of caustic alkaline or carbonates to produce the 2-aminod-methoxy pyrimidine compound, melting point 80°C to 82°C, (benzene). 

Figure 9-1 Sites of feedback inhibition in carbamyl phosphate metabolism of E. coli. Note that aspartate trascarbamylase is the first enzyme on the unique pathway to pyrimidine compounds.

Triazolo[4,5-d]pyrimidine compounds, (VII), prepared by Harden (7) were effective in controlling platelet-mediated occlusion and useful in treating thrombolysis compromised by reocclusion. 

In addition to major nucleosides and bases, modified nucleosides and bases have also been isolated from tRNA hydrolysates and in physiological fluids of man. Unlike the major nucleic acid components, the methylated or otherwise structurally altered purine and pyrimidine compounds are not recycled in the salvage pathways but are excreted. It has been suggested that the measurement of these modified compounds may provide an indicator of the rate of tRNA metabolism. Furthermore, the altered patterns of excretion for these compounds may be used as biomarkers for the detection of disease states and aberrations in metabolic pathways. 

Although it has been difficult to rationalize the retention behavior of purine and pyrimidine compounds based upon their chemical structure and physiochemical characteristics. Brown and Grushka (B26) have recently formulated some rules for predicting retention behavior of these compounds. These rules are summaried below ... 

In cases where there is a suitable leaving group, such as chloro, alkoxy, or amino, the nucleophilic attack at the activated vinyl system of the C—C —C fragment will be followed by the reestablishment of the C—C double bond, the result being a vinylic substitution. In these cases the final cyclization affords the pyrido[2,3-d]pyrimidine compound, or otherwise its dihydro derivative. 

R.B. Bradbury, N.C. Hancnox, and H.H. Haft, Reaction between acetone and ammonia the formation of pyrimidine compounds analogous to the aldoxanes of spath, J. Chem. Soc. 1947, 1394-1399. 

Figure 6-32. In the upper half the match is poor in this pyrimidine compound the phosphine phenyl rings do not match at all. HEGLEK is Ref. [49] and HEGLEKOl is Ref. [50]...

Pulse Radiolysis of DNA and Related Pyrimidine Compounds Reactions of the OH- Free Radical... 

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