The retrosynthetic analysis of the dinucleoside 1 structure suggested the coupling reaction between the tosyl derivative 17 previously described by us (Scheme 2) [14], and the readily accessible 5′-amino-2′,3′-isopropylidene adenosine [21]. The direct N-alkylation at room temperature did not afford the secondary amine in satisfactory yields and when increasing the temperature to enhance the reactivity of the primary amine, we noticed degradation of 17. To circumvent the lack of reactivity of primary amines, a synthetic method using nitrobenzenesulfonamides (Ns-amides) as both a protecting and activating group has been developed by Fukuyama [22]. The main advantage of this nosyl strategy is that both alkylation and deprotection proceed under mild conditions. Recently, the 2-nitrobenzenesulfonamide has been used successfully to synthetize transition state analogs of DNA methylation based on the coupling of cytosine analogs to adenosine [15]. In the same way, we envisaged the coupling between 17 and the 5′-nosyl adenosine 18 to obtain the dinucleoside 1 (Scheme 2). The building block 18 was prepared in 74% yield by reacting 4-nitrobenzenesulfonyl chloride [22] that has a similar reactivity to 2-nitrobenzenesulfonyl chloride as used in Ref. [15], with 5′-amino-2′,3′-isopropylidene adenosine prepared upon published procedures [23]. N-alkylation of Ns-amide 18 with 17 in the presence of K2CO3 in DMF at room temperature did not afford the expected dinucleoside 19, even at high temperature. Nevertheless, according to the literature [24], the addition of a catalytic amount of KI to the reaction mixture was beneficial to give 19 in 74% yield. Facile deprotection of 19 by treatment with a nucleophilic thiolate produced the desired secondary amine 20 in high yield. Removal of sugar protecting groups has been accomplished in acidic medium to give dinucleoside 1 in 76% yield. Likewise, the acidic treatment was applied to the intermediate Ns-amide 19 to afford the 4-nitrobenzenesulfonamide-containing dinucleoside 9 in 34% yield (Scheme 2).