Synthesis of certain N ‐ and C ‐alkyl purine analogs

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(4 H )‐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(7 H )‐one 25a and 25b , respectively. A similar condensation of 3‐amino‐6‐aminomethyl‐1,2,4‐triazin‐5(4 H )‐one ( 23 ) with heptanoic acid, followed by ring annulation, readily gave 2‐amino‐7‐ n ‐hexylimidazo[5,1‐ f ][1,2,4]triazin‐4(3 H )‐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‐1 H ,3 H ‐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.