Synthesis of certain N‐ and C‐alkyl purine analogs

Abstract

A number of N‐ and C‐alkyl derivatives of selected guanine analogs have been synthesized as potential antiviral agents. n‐Pentyl, n‐hexyl and 6‐hydroxyhexyl derivatives in the imidazo[1,2‐α]‐s‐triazine, 9–11, imid‐azo[1,2‐α]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. Dehydra‐tive 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 6‐amino‐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‐aminomethyl‐1,2,4‐triazin‐5(4H)‐one (23) with heptanoic acid, followed by ring annulation, readily gave 2‐amino‐7‐n‐hexylimidazo[5,1‐f][1,2,4]triazin‐4(3H)‐one (25c). Bromination of 25c with N‐bromosuccini‐mide afforded the corresponding 5‐bromo derivative 26. Alkylation of the in situ generated sodium salt of 4‐methoxycarbonylmethyl‐5‐methoxycarbonyl‐2‐oxo‐1H,3H‐imidazole (27) with 1‐bromohexane gave the N‐1 alkylated product 31. Manipulation of the functional groups in 31 and further hydrazine mediated ring annulation furnished 5,6‐diamino‐1‐n‐hexyl‐3‐methylimidazo[4,5‐c]pyridine‐2,4‐dione (39). Catalytic hydrogena‐tion of 39 gave 7‐methyl‐8‐oxo‐9‐hexyl‐3‐deazaguanine (40), a congener of the immunostimulator 7‐methyl‐8‐oxoguanosine. Copyright © 1993 Journal of Heterocyclic Chemistry