Synthesis of certainN- andC-alkyl purine analogs

Autor: Birendra K. Bhattacharya, Yogesh S. Sanghvi, T. Sudhakar Rao, Ganapathi R. Revankar, Arthur F. Lewis, Roland K. Robins
Rok vydání: 1993
Předmět:
Zdroj: Journal of Heterocyclic Chemistry. 30:1341-1349
ISSN: 1943-5193
0022-152X
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: