Pyrimidone ring

An alternate scheme for preparing these compounds starts with a prefabricated pyrimidone ring. Aldol condensation of that compound (95), which contains an eneamide function, with pyridine-3-aldehyde (80), gives the product 96. Catalytic hydrogenation gives the product of 1,4 reduction. The resulting pyrimidinedione, of course exists in the usual tautomeric keto (97a) and enol (97b) forms. Reaction with phosphorus oxyxchloride leads to the chloro derivative 98. Displacement with methoxide gives 99. Reaction of this last intermediate with the furylalkylamine derivative 92 leads to the H-2 blocker lupitidine (100) [22]. 

The pyrimidone ring system is not fully aromatic, since such compounds exist as amides, rather than hydroxypyrimidines, and the rr-system does not extend fully around the ring. In the case of the uracils, the 5,6-double bond possesses allylic character, and various relatively stable adducts can be obtained, for example, with bromine or chlorine water [210, 486—488]. Catalytic reduction across the 5,6-double bond is also readily accomplished [441, 489—491]. 

The most important feature of organocobalt cyclizations is that a variety of functionalized products can be obtained, depending on the nature of the substrate and the reaction conditions. The most common transformation has been formation of an alkene by cobalt hydride elimination. Alkenes are often formed in situ during the photolysis, and with activated alkene acceptors the formation of these products by cobalt hydride elimination is very facile. Scheme 31 provides a representative example from the work of Baldwin and Li.143 The alkene that is formed by cobalt hydride elimination maintains the correct oxidation state in the product (54) for formation of the pyrimidone ring of acromelic acid. Under acidic conditions, protonation of the cyclic organocobalt compound may compete 144 however, if protonated products are desired, the cyclization can probably be conducted by the reductive method with only catalytic quantities of cobalt (see Section 4.2.2.2.2). 

The pyrimidone ring of pyrimido[l,6-nucleophilic attack at position 1. Compound 488 (R = H) gave azepine derivative 487 when heated with p-phenylethylamine or in a basic buffer solution (80KGS1120). 

A synthesis of sildenafil, which contains a bicyclic system (a l//-pyrazolo[4,3- f pyrimidine) isomeric with that of a purine, starts with a routine synthesis of a pyrazole (cf. 25.12.1.1) followed by M-methylation and ring nitration. Functional group manipulation provides a pyrazole equivalent to AICA (27.11.1.2) from which the pyrimidone ring is formed via reaction with an aromatic acid chloride. 

An ingenious modification of the general method uses 5,6-diaminouracil as a masked unsaturated 1,2-diamine the products can be hydrolysed with cleavage of the pyrimidone ring finally arriving at amino-pyrazine acids as products. ... 

C-Glycosylation of a thiophene has been reported <88TL3537>. SnCU-catalyzed reaction of N-formyl-4-aminothiophene-3-carboxylic ester with 1-O-acetyl-tri-O-benzoyl- -D-ribofuranose gave the product (59) in 43% overall yield, with a p/a ratio of 2.4. Fusion of a pyrimidone ring on the thiophene in (59) gave a C-nucleoside inosine analogue. 

Reduction of the pyrimidone ring in quinazolinone systems can be easily achieved. For example, hydrogenation of 110 under conventional conditions gave the hydroquinazolinone 111 as reported by Drizin and co-workers <01JMC1971>. 

This gives the 4-pyrimidone ring, which is converted into the 4,5-dichloro-6-(l-fluoroethyl)pyrimidine by the action of sulfuryl chloride in the presence of dimethylformamide (DMF) [68]. The chlorine on the 4-position of the pyrimidine ring is substituted with the side chain 2-[4-(trifluoromethyl)phenyl]ethylamine through a nucleophilic substitution reaction [63]. The side chain 2-[4-(trifluoro-methoxy)phenyl]ethylamine is prepared by chloromethylation of trifluorome-thoxybenzene followed by displacement of the chlorine atom with cyanide and reduction of the nitrile with Raney nickel [69]. 

Toledo, L. M., Musa, K., Lauher, J. W, and Fowler, F. W., Development of strategies for the preparation of designed soUds. An investigation of the 2-amino-4(IH)-pyrimidone ring system for the molecular self-assembly of hydrogen-bonded a- and P-networks, Chem. Mater., 7, 1639, 1995. 

From an analysis of the product obtained in preparative electrolysis of pyrimidone, in conjunction with other data, it has been suggested that a dimer with the carbon-nitrogen double bond of the pyrimidone rings hydrogenated is formed as a result of the electrode reaction [58]. 

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