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Glycosylation of 6-(substituted-imidazol-1-yl)purine sodium salts with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride proceeds with regiospecific formation of the N9 isomers. Base substrates with lipophilic substituents on the C6-linked imidazole moiety are more soluble in organic solvents, and the solubility is further increased with binary solvent mixtures. Selective solvation also diminishes the extent of anomerization of the chlorosugar. Stirred reaction mixtures of the modified-purine sodium salts generated in a polar solvent and cooled solutions of the protected 2-deoxysugar chloride in a nonpolar solvent give 2′-deoxynucleoside derivatives with N9 regiochemistry and enhanced β/α configuration ratios. Application of the binary-solvent methodology with 2-chloro-6-(substituted-imidazol-1-yl)purine salts in cold acetonitrile and the chlorosugar in cold dichloromethane gives essentially quantitative yields of the N9 isomers of β-anomeric 2′-deoxynucleoside intermediates. Direct ammonolysis (NH3/MeOH) of such intermediates or benzylation of the imidazole ring followed by milder ammonolysis of the imidazolium salt gives high yields of the clinical anticancer drug cladribine (2-chloro-2′-deoxyadenosine). [ABSTRACT FROM AUTHOR]