The reaction of (2R)-2-methyl-1,4-butanediamine (I) with potassium tetraidoplatinate (II) gives diaminediiodoplatinum complex (III), which is converted to diamineplatinum nitrate (IV) with silver nitrate. The nitrate (IV) is reacted with sodium cyclobutanedicarboxylate (V).

The synthesis of radiolabeled NK-121 has been described: 192Pt is submitted to thermal neutron irradiation and the resulting radiolabeled Pt is treated with aqua regia to give H2PtCl6, which by treatment with KCl is converted to the corresponding potassium salt (II). The reaction of (II) with hydrazine in water yields potassium tetrachloroplatinate (III), which by treatment with 2(R)-methylbutane-1,4-diamine (IV) and KI in water affords the corresponding diiodo platinum complex (IV). Finally, this compound is treated with cyclobutane-1,1-dicarboxylic acid and silver nitrate in aqueous 0.1 N NaOH.

The synthesis of [14C]-labeled CI-973 (NK-121) has been described: The reaction of 3-bromo-2(R)-methylpropanol (I) with sodium azine in hot DMSO gives the corresponding azide (II), which by hydrogenation with H2 over Pd/C in methanol in the presence of tert-butyl dicarbonate affords 3-(tert-butoxycarbonylamino)-2(S)-methylpropanol (III). The acylation of (III) with methanesulfonyl chloride and triethylamine in dichloromethane yields the corresponding mesylate (IV), which is treated with [14C]-potassium cyanide in hot DMSO to give [1-14C]-4-(tert-butoxycarbonylamino)-3(R)-methylbutanenitrile (V). The reduction of (V) with H2 over RaNi in methanol-NH3 affords the partially protected diamine (VI), which by treatment with dild. HCl in ethyl acetate yields the free diamine (VII). The reaction of (VII) with potassium tetraiodoplatinate in water gives the polymeric platinum complex (VIII), which is treated with silver nitrate in water to obtain the monomeric diaqua complex (IX). The reaction of (IX) with KI in water gives the monomeric diiodo complex (X), which is finally treated with silver cyclobutane-1,1-dicarboxylate (XI) in hot water.