Quinoxaline derivative synthesis

All reactions were carried out in an oven-dried round-bottom flask with magnetic stirring under an open atmosphere. Reagents were purchased from MilliporeSigma, Acros, or Alfa Aesar. Before use, solvents were treated with 4 Å molecular sieves. The purification of the reaction products was carried out by chromatography using CHEM-LAB silica gel (230–400 mesh). The purity of the quinoxaline derivatives was tested by HPLC, and only compounds with more than 95% purity were used for the experiments. ¹H NMR and ¹³C NMR spectra were recorded with tetramethylsilane as an internal standard at ambient temperature on a Bruker 400 Avance III HD for ¹H NMR and a 100 MHz for ¹³C NMR. Chemical shifts were reported in parts per million and coupling constants in hertz. Splitting patterns were designated as a singlet, broad singlet, doublet, triplet, doublet of a doublet, or triplet of a triplet. Splitting patterns that could not be interpreted or easily visualized were designated as multiple. Spectroscopic data of all the compounds matched with the previously reported data.

In general, a stoichiometric quantity of substituted aromatic diamine was condensed in the presence of a strong acidic condition, which undergoes oxidation to furnish the quinoxaline derivatives. The progress of the reaction was monitored by thin layer chromatography. Once the complete consumption of the starting material was confirmed, the reaction mixture was quenched with a saturated solution of sodium bicarbonate, extracted twice with ethyl acetate, and dried over anhydrous sodium sulfate. The combined organic layer was then evaporated under vacuum, and the resulting crude was purified by column chromatography on silica gel with an increasing concentration of ethyl acetate in hexane to afford the desired compound.

Some of the quinoxaline derivatives were purchased from MilliporeSigma, Acros, or Alfa Aesar (Supplemental Table 1).

Stock solutions were prepared in DMSO at 50–100 mM. The working solutions never contained more than 1% DMSO.