Pyrimidine ring amides

This pyridine-pyrimidine ring transformation has also been observed on treatment of 2-bromoquinoline with potassium amide in liquid ammonia, 2-methylquinazoline being obtained (67RTC187). Similarly, 8-bromo-l,7-phenanthroline gives 2-methyl-l,3,5-triazaphenanthrene (83JHC447)... 

Soai and co-workers reported the oxidative cleavage of the pyrimidine ring in pyrimidines 106 to produce chiral acetamides 107 along with amides 108 with excellent retention of optical purity <00H151>, This is claimed to be the first such oxidative cleavage of the pyrimidine ring. 

It is of interest to mention that the addition of the amide ion to C-2 of the pyrimidine ring is in general not a favored reaction. There is sound NMR evidence that addition of the amide ion to the parent system pyrimidine occurs exclusively at C-4 there is almost no indication for addition at C-2 (72JA682). For a more detailed discussion on this topic, see Section II,C,l,a. 

When amination-without-quenching is carried out with N-labeled potassium amide/liquid ammonia and the degree and position of labeling in both amino products are determined, it appears that the incorporation of the label in the pyrimidine ring of 2-amino-4-phenylpyrimidine 61 has decreased from 92 to 52% see Table II.8. Thus, not only the yield of the 2-amino product is lower, but also the fraction that is formed via a ring opening-ring closure sequence [Sn(ANRORC) mechanism]. 

Amination of 5-phenylpyrimidine with N-labeled potassium amide revealed that no label was incorporated in the pyrimidine ring of 6-amino-5-phenylpyrimidine this means that exclusively 72 has been formed. 

The pyrimidine ring is made up of three components the nitrogen atom N-1 and carbons C-4 to C-6 are derived from aspartate, carbon C-2 comes from HCOa", and the second nitrogen (N-3) is taken from the amide group of glutamine. 

However, perhaps the simplest route to quinazoline derivatives involves the heating of 2-aminobenzamides with formic acid to give 4(3//)-quinazolinones, where the formic acid provides the solvent, the C-2 synthon, and the acid catalysis of the ring-closure step. For example, in the synthesis of the imidazoquinazolinone 798, both the imidazo and pyrimidine rings were formed simply by heating the triamino amide 797 in formic acid for 2h <1996JME918>. 

The pyrimidine rings in the pyrido[2,3- - and [3,2-i7ipyrimidinones 325 and 327 were formed by heating the corresponding amides 324 and 326 at reflux in pyridine and aqueous NaOH, respectively (Equations 27 and 28) <1994WO9405661, 2000USP6060477>. 

The formation of a pyrimido[5,4-f][l,2]thiazine by annulation of a pyrimidine ring onto a benzoH[l,2]thiazin-4-one has been reported, involving condensation with dimethylformamide dimethyl acetal followed by Bredereck s reagent (Scheme 90), and reaction of the resultant vinylogous amide with guanidine <2005W02005/037843>. Essentially, the same approach has been used to prepare annulated forms of the isomeric pyrimido[4,5-< ][l,2]thiazines, as outlined in Scheme 91 <1998W098/28281>. 

Reaction of 2-oxopyrido[l,2-a]pyrimidines (33) with /f-oxo esters in dimethylformamide in the presence of l,5-diazabicyclo[4,3,0]non-5-ene at room temperature, or with /Toxo amides in the presence of zinc chloride in boiling ethanol, affords the pyridone derivatives (199). Cleavage of the pyrimidine ring can also be effected with amines.28... 

Imidazolecarboxitnidamides are readily available by degradation of the pyrimidine ring of adenines. Ortho esters, amides, and acid anhydrides are used for the condensation reaction. Thus, 2-(trifluoromethyl)adenine (1) is prepared from 5-aminoimidazole-4-carboximidamide dihydrochloride by refluxing with trifluoroacetamide. ... 

Extensive investigation of amide-induced amination of purine and its derivatives has shown that the parent compound (purine) as well as its 2-methyl and 8-methyl derivatives react with potassium [ - Njamide in ammonia to undergo exclusive amination at C6 without incorporation of the N label into the ring (Chichibabin reaction). Amination of 2-fluoro-, 2-chloro-, and 2-(methylsulfanyl)purine 7, and 2-chloro-6-phenylpurine with potassium [ N]amide in ammonia, however, gives purin-2-amines with complete incorporation of the N label in the pyrimidine ring. 

FIGURE 9.7 Pyrimidine biosynthetic pathway. The pathway of pyrimidine biosynthesis involves sbc steps and results in the production of uridine 58-monophosphate. Folate is not used in this pathway The pathway commences with the transfer of the amide nitrogen of glutamine to bicarbonate to produce caibamy I phosphate. This molecule then reacts with aspartate to form the beginnings of the siK-membered pyrimidine ring. 

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