Pyrido pyrimidone

Chlorination of 2-hydroxy-4//-pyrido[l,2-n]pyrimidin-4-one with NCS in a mixture of AcOH and TFA at room temperature for 72 h yielded a 3-chloro-2-hydroxy derivative (95JMC4687). Bromination of 2-chloro-4//-pyrido[l, 2-n]pyrimidone with Br2 in a mixture of CH2CI2 and pyridine at room temperature for 15 min gave a 3-bromo derivative (00BMC751). 

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). 

The most important method for the introduction of halogen substituents into pyrido[2,3-c/]-pyrimidines 5 is the reaction of pyridone or pyrimidone functions with halogenating agents such as phosphoryl halides39-77,79 131, l34,200,237,332 or thionyl chloride238,333,569 to furnish the corresponding halogen compounds 6. 

Treatment of 2-azido-pyrido[ l,2-a]pyrimidone (317), which can exist only in an azide form, with base resulted in simultaneous cleavage of the pyrimidine ring and closure of the azidoazomethine moiety [Eq. 

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