Non-costly and readily available inosine was transformed into 2′,3′,5′-tri-O-acetyl-6-chloropurineside via acetylation of sugar and chlorination of C6 carbonyl group. Then the nitro group was introduced into C2 of 2′,3′,5′-tri-O-acetyl-6-chloropurineside in CH2Cl2 with n-Bu4NNO3 and trifluoroacetic anhydride. The final product 2,6-dichloropurine riboside was synthesized in 63% total yield in HCl/EtOH solution which de-protected the acetyl groups and chlorinating the nitro group in one pot and two steps. The effects of nitro precursor, chloro precursor and reaction scales on the yields were investigated. The yield was maintained even on the 200 g scale.