A new 2′-deoxyuridine modification, 3′,5′-bis-(dimethyl-tert-butylsilyl)-5-(3-(2-(dimethylamino)ethoxy)-3-methylbutyn-1-yl)-2′-deoxyuridine was effectively synthesized in four easy steps. Its reactivity toward a range of cyclic oxonium adducts of closo-dodecaborate and cobalt-bis-dicarbollide boron clusters was studied. The cleavage reactions of cluster oxonium rings by the N,N-dimethylamino group of the modified nucleoside led to 5-ethynyl-2′-deoxyuridine conjugates with [B12H12]2− and [Co(C2B9H11)2]−, respectively. Cytotoxicity of these new conjugates in several cell lines was examined. Closo-dodecaborate conjugates showed low cytotoxicity in all examined cell lines, an advantageous and preferred property for potential boron delivering drugs for the boron neutron capture therapy (BNCT) of tumors.