Pyridopyrimidines electrophilic

REACTIVITY AT RING ATOMS IN PYRIDOPYRIMIDINES 2.15.3.1 Electrophilic Attack at Ring Carbon... 

REACTIVITY OF SUBSTITUENTS IN PYRIDOPYRIMIDINES 2.15.4.1 Electrophilic Attack on Substituents... 

Alkyl groups attached to pyridopyrimidines adjacent to a nitrogen are activated , i.e. they are readily deprotonated and react with electrophilic reagents as their anions, or resonance stabilized equivalents, e.g. (64). This ready deprotonation, of course, leads to facile exchange of the alkyl protons for deuterium (Sections 2.15.2.2.1, 2.15.4.2), but, in... 

Carboxylic acid derivatives on pyridopyrimidine rings appear to undergo normal reactions with electrophilic reagents, e.g. the 6-amide (70) is dehydrated to the 6-nitrile with phosphorus oxychloride. 

Factors that affect the rate-determining step (171 172) will influence the overall rate of reaction. A stronger nucleophile, such as hydrazine, is certainly more efficient than hydroxide, but no studies have been reported on the alternative variation of the electrophilicity of the 4-carbonyl group. Ring-opening may occur at either the 3 4.35,91,136,136 qj. 1 2-bouds in pyridopyrimidine-2,4(lH,-... 

Hydroxy-2-methyl-4//-pyrido[ 1,2-a]pyrimidin-4-one 365 gave 8-sub-stituted derivatives in a reaction with different electrophilic reagents (Scheme 28) (92KGS1660). Nitration gave 8-nitro-9-hydroxy-2-methyl-pyridopyrimidin-4-one 326. Reaction with iodine afforded 8-iodo-... 

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