Synthesis and Characterization of Sobetirome Derivatives

¹H and ¹³C NMR were taken on a Bruker 400 MHz. All spectra were calibrated to the NMR solvent reference peak (chloroform-d or d₃-MeCN). ¹H coupling constants (JHH, Hz) are reported as follows: chemical shift, multiplicity (br = broad, s = singlet, d = doublet, sept= septet, m = multiplet, dd = doublet of doublets), coupling constant, and integration. High-resolution mass spectrometry (HRMS) with electrospray ionization was performed by the Bioanalytical MS Facility at Portland State University. Sobetirome and d₆-sobetirome were synthesized as previously described.^{40 (link), 41 (link)} All other reagents were purchased from Fisher, Sigma, or TCI and used as received. Analytical HPLC analysis was performed on a Varian ProStar HPLC with a Grace Altima C18, 5 μm column (4.6 × 250 mm) with a gradient (Solvent A: Water + 0.1% TFA; Solvent B: MeCN + 0.1% TFA) for B: 20–100% 0–20 minutes, 100% B 20–25min, 100%−20% B 25–26min, hold 20% B 26–30 min. Flowrate was 1 mL/min. Purity analysis of final compounds was determined to be >95% by HPLC (A_235nm). HPLC traces can be found in the Supplemental Information.