SYNTHESIS OF CERTAIN N-ALKYL AND C-ALKYL PURINE ANALOGS

A number of N- and C-alkyl derivatives of selected guanine analogs hav e been synthesized as potential antiviral agents. n-Pentyl, n-hexyl an d 6-hydroxyhexyl derivatives in the imidazo[1,2-a]-s-triazine, 9-11, i midazo[1,2-a]pyrimidine, 13-17, and thiazolo[4,5-d]pyrimidine, 19-21, ring system have been prepared by the direct alkylation of the sodium salt of the appropriate aglycon with the respective alkylbromides. Deh ydrative coupling of 3-amino-6-hydrazino-1,2,4-triazin-5(4H)-one (22) with either hexanoic acid or heptanoic acid, and further ring closure of the reaction products 24a and 24b provided the n-pentyl and n-hexyl derivatives of mino-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one 25a and 25b, respectively. A similar condensation of 3-amino-6-aminomethy l-1,2,4-triazin-5(4H)-one (23) with heptanoic acid, followed by ring a nnulation, readily gave no-7-n-hexylimidazo[5,1-f][1,2,4]triazin-4(3H) -one (25c). Bromination of 25c with N-bromosuccinimide afforded the co rresponding 5-bromo derivative 26. Alkylation of the in situ generated sodium salt of onylmethyl-5-methoxycarbonyl-2-oxo-1H,3H-imidazole (27 ) with 1-bromohexane gave the N-1 alkylated product 31. Manipulation o f the functional groups in 31 and further hydrazine mediated ring annu lation furnished 1-n-hexyl-3-methylimidazo[4,5-c]pyridine-2,4-dione (3 9). Catalytic hydrogenation of 39 gave 7-methyl-8-oxo-9-hexyl-3-deazag uanine (40), a congener of the immunostimulator 7-methyl-8-oxoguanosin e.