ADENINE ISOSTERES WITH BRIDGEHEAD NITROGEN .1. 2 INDEPENDENT SYNTHESES OF THE [1,2,4]TRIAZOLO[1,5-ALPHA][1,3,5]TRIAZINE RING-SYSTEM LEADINGTO A RANGE OF SUBSTITUENTS IN THE 2-POSITION, 5-POSITION AND 7-POSITION

Condensation of a 3-substituted 5-amino-1,2,4-triazole with an N-cyano carbonimidate (RX)(2)C=NCN, yields the title compounds, in most cases as a mixture of isomers; separation and elaboration then gives [1,2,4] triazolo[1,5-a][1,3,5]triazines bearing a range of substituents in the 5 and 7 positions. Under milder reaction conditions, less stable isom eric products (e.g., the [1,2,4]triazolo[4,3-a][1,3,5]triazine ring sy stem or an uncyclised N-cyano intermediate) can be isolated and shown to rearrange to the [1,5-a] isomer. A second synthesis is described in which a suitably substituted 2-hydrazido-1,3,5-triazine is cyclodehyd rated to give a single isomer with identical substituents in the 5 and 7 positions; the large difference in reactivity between these allows selective replacement at the 7-position with nucleophile. Additionally , the second synthesis is more readily adaptable to the introduction o f substitutents at the 2 position of the bicyclic nucleus. 7 yl)-5-phe noxy[1,2,4]triazolo[1,5-a][1,3,5]triazine 12a is prepared independentl y by both synthetic sequences and its structure verified by X-ray crys tallographic analysis, H-1 NMR, C-13 NMR and MS data are also presente d in support of the proposed structures.