Pyridopyrimidines nucleophilic

As in the pyridopyrimidines, selective nucleophilic substitution reactions at reactive ring positions have been a fruitful source of pyridopyridazines. 

Pyrido[3,4-d]pyrimidine-2,4-dione synthesis, 3, 215 Pyridopyrimidines, 3, 201 iV-alkylations, 3, 206 biological activity, 3, 260-261 1-electron reductions, 3, 207 IR spectra, 3, 204 mass spectra, 3, 204 MO calculations, 3, 204 NMR, 3, 202, 203 nucleophilic substitution, 3, 213 8-nucleosides synthesis, 3, 206 physical properties, 3, 201-205 protonation, 3, 206 radical reactions, 3, 215 reactions with water, 3, 207 reduced... 

A large number of nucleophilic substitution reactions involving interconversions of pyridopyrimidines have been reported, the majority of which involve substituents in the pyrimidine ring. This subject has been reviewed previously in an earlier volume in this series which dealt with the theoretical aspects of nucleophilic re-activiti in azines, and so only a summary of the nucelophilic displacements of the substituent groups will be given here. In general, nucleophilic substitutions occur most readily at the 4-position of pyrido-... 

In common with other fused pyrimidines, the pyridopyrimidines are susceptible to the nucleophilic addition of water across the 3,4-bond. This is the phenomenon of covalent hydration... 

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,-... 

Triazanaphthalene (449) is the most unstable of the pyrido-pyrimidines to ring-degradation at pH 2 or pH 7.7 The 4-oxo derivative was converted into the 4-thioxo compound via nucleophilic displacement of the acyloxy intermediate formed with phosphorus pentasulfide. The 4-carboxymethylthio-pyridopyrimidine underwent some substitution by hydroxide ion but primarily gave the ring-opening reaction, which is facilitated by resonance activation of the 2-position by the 6-aza moiety. 

In the above reactions of enamine derivatives with oxazolidines and oxazinanes, pyridine systems did not constitute direct targets but were formed, in a few cases, by air oxidation of initially formed dihydropyridine derivatives. Oxazolidines 30, possessing electron-withdrawing groups in C-2 substituents, exist mainly as tautomeric acyclic enamines 28 (Section II.C.2), which in the presence of an acid would also generate iminium cations such as 54 that should react with nucleophiles. Thus, it has been found that such oxazolidines in presence of an acid, react with acyclic, cyclic, and heterocyclic enamine derivatives in 1 1 stoichiometry to provide a unique synthesis of pyridine, quinolinone, and pyridopyrimidine derivatives (98T935). 

A number of reports concern the attack of nucleophiles on perfluoro-olefins to give cumulenes or heterocumulenes, which in turn imdergo nucleophilic attack to give heterocyclic compounds with perfluoroalkyi substituents. o-Phenylenedi-amine reacts with hexafluoropropene to give 2-(o j8j8>tetrafluoroethyl)benzimidazole (301) ketenimine intermediates have also been utilized in the formation of quinolines (302) (see p. lll) 89.59o j,y intramolecular cyclization, and (303) (see p. 112) by intermolecular cyclization, naphthyridines (304), pyridopyrimidines (305), and isoquinolines (306). The pyran derivative (307) is formed via isomerization of an allene intermediate (see p. 100). 3-Fluoro-2-isopropyl-l,2,4-thiadiazolin-... 

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