Preparation of new N6, 9-disubstituted 2-phenyl-adenines and corresponding 8-azaadenines.: A feasibility study for application to solid-phase Synthesis. I

• Published in: Journal of heterocyclic chemistry 2004-07, Vol.41 (4), p.575-580
• Main Authors: Biagi, Giuliana, Giorgi, Irene, Livi, Oreste, Pacchini, Federica, Scartoni, Valerio, Salerni, Oreste Leroy
• Format: Article
• Language: English
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.5570410415

A suitably substituted pyrimidine 1 was converted to a number of title compounds. Nucleophilic substitu tion involving the chlorine atoms in 1 by treatment with phenylmethanethiol yielded 2 or 3, depending on the reaction temperature. Treatment of 3 with an amine afforded 6‐phenylmethanesulfanyl‐N4‐substituted‐2‐phenyl‐pyrimidine‐4,5‐diamines 4–7. These pyrimidines were converted into 2‐phenylpurines 8–11 and 2‐phenyl‐8‐azapurines 12–14, by treatment with triethyl orthoformate in the presence of hydrochloric acid (or acetic anhydride), or with potassium nitrite and acetic acid respectively. The thioether function on C(6) was then converted into a sulfonyl group by oxidation with m‐chloroperoxybenzoic acid affording purines 15–18 and their 8‐azaanalogs 19–21; these compounds, as crude products, were treated with an amine to yield the corresponding adenines 22–25 or 8‐azaadenines 26–31. All reactions were performed under conditions com patible with the possible use of a thiomethyl resin in place of phenylmethanethiol to bind the pyrimidine ring of 1 to a solid phase.