Process for preparing N-9 substituted purine analogs

摘要

In the present invention, there is disclosed a process for preparing N-9 substituted purine analogs of the general formula III, in which Z represents a hydrogen atom or an amino group, Q denotes an amino group, alkylamine containing 1to 15 carbon atoms, dialkylamine having 1 to 15 carbon atoms, a heterocyclic amine, arylamine, diarylamine, a hydroxy group, an alkoxy group containing 1to 15 carbon atoms, a thio group, an alkylthio group containing 1to 15 carbon atoms, an azido group and Ri1 represents alkyl having 1 to 15 carbon atoms, an alkenyl containing 2 to 15 carbon atoms, an alkynyl having 2 to 15 carbon atoms, a cycloalkyl containing 3 to 10 carbon atoms, a cycloalkenyl having 3 to 10 carbon atoms, an aryl group, a heteroaryl group, wherein the invented process is characterized in that in the first step a primary amine or a diamine with the substituent Ri1, as described above or a salty thereof, is brought as a substrate into a reaction with an agent represented by a pyrimidine precursor of the general formula I, in which Z is hydrogen or an amino group, in a suitable solvent in the presence of a non-nucleophilic base, under heating to build-up successively on the amino group a purine base being represented by the substituted 6-chloropurine of the general formula II, wherein the Z and R1 substituents are the same as indicated above whereby the nitrogen atom of such amino group becomes the position N-9 of the produced nucleobase; in the second step a nucleophilic agent is selectively added to the reaction mixture without isolating the chloropurine intermediate and the so created substituted chloropurine analog of the general formula III is then separated. The reaction intermediate, 9-substituoted 6-chloropurine can also be obtained without execution of the second reaction step directly from the raw reaction mixture. The compounds of the general formula II are intermediates for the preparation of medicaments while the compounds of the general formula III are usable as medicaments.