Amination of Aromatic Heterocyclic Lactam Systems

The amination of aromatic hydroxy-N-heterocycles is a standard reaction in medicinal and agricultural chemistry and has heen reviewed [36]. The hitherto commonly used two-step procedure for amination of hydroxy-N-heterocycles, starts with conversion into the chloro-N-heterocycles, e.g. by treatment of the hydroxy-N-heterocycle with POCI3, PCI5, or SOCI2, followed by reaction with the amine moiety. This methodology has several drawbacks however, for example  

the difficulty of isolating the pure aromatic chloroheterocycles during work up from the viscous phosphoric acid-polyphosphoric acid on employing POCI3 or PCI5 and 

Reaction of 2,4-(lH,3H)-quinazolinedione 250 for 8h at 130°C with two equivalents of N-2-hydroxyethylpiperazine 251 (the alcohol group of which is in-situ protected by silylation), HMDS 2, and catalytic amounts of TSOH H2O, and subsequent transsilylation with boiling methanol, affords 68% of the monoaminated product 252 and methoxytrimethylsilane 13 a. Reaction of 250 with fivefold excess of N-2-hydroxyethylpiperazine 251 in the presence of octamethylcyclotetrasilazane 

Silylation-aminations of a variety of other hydroxy-N-heterocycles, for example 4(lH)-pyridinone, 2(lH)-pyrimidone, uracil, 2(lH)-quinoline, and 9(10H)-acridone are described in the full paper, which was published in English [27]. 

The advantages of the one-step silylation-amination of hydroxy-N-heterocycles are demonstrated by the amination of 2-methylpyrido[3,4-d]pyrimidin-4-one 261. Whereas silylation-amination of 261 with three equivalents of benzylamine- 

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Amination of Aromatic Heterocyclic Lactam Systems (Synthesis of Cytidines)... 

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