Practical Synthesis Strategy for NIR-II Cyanine Fluorophores: Laboratory-Scale Development and Structural Characterization of IR 1048

As a representative NIR-II cyanine fluorescent dye, IR 1048 exhibits excellent optical properties and biocompatibility. However, its synthesis and structural characterization have not been systematically investigated until now. In this paper, a decagram-scale preparation method that avoids chromatographic purification and the use of harmful reagents was developed. IR 1048 was obtained in seven steps with an overall yield of 31.2%. Meanwhile, structural characterization was also accomplished by HRMS and 1 H NMR using a mixed deuterated solvent system (CDCl 3 /CD 3 OD).