PROCESS FOR THE PREPARATION OF 9-SUBSTITUTED GUANINE DERIVATIVES

摘要

PCT No. PCT/DK90/00077 Sec. 371 Date Sep. 20, 1991 Sec. 102(e) Date Sep. 20, 1991 PCT Filed Mar. 19, 1990 PCT Pub. No. WO90/11283 PCT Pub. Date Oct. 4, 1990.A process for the preparation of 9-substituted quanine derivatives of general formula (I), in which R is C1-C4-alkyl optionally substituted with one or more hydroxy groups, or R is ( alpha ), benzyl, ribosyl, 2'-deoxyribosyl or (CH2)n-OR1 where n is 1 or 2, and R1is CH2CH2OH or ( beta ) or salts thereof, in which a 1-substituted5-(thiocarbamoyl)amino-1H-imidazole-4-carboxamide of general formula (III), where R has the same meaning as in formula (I), is cyclized: a) by treatment with a heavy metal salt of the group of Cu-, Ag-, Pb- and Hg-salts in an aqueous alkaline medium containing at least for equivalents of OH-ions at a temperature form about 0 DEG C. to the reflux temperature, or b) by treatment with a peroxy compound in an aqueous alkaline medium at a temperature of about 0 DEG -30 DEG C., whereafter (I) is isolated by treatment with a acid and, if desired, is converted into a salt. The invention further comprises intermediates for use in the preparation of the above-mentioned compounds.