Isco combiflash rf system

All commercial reagents and solvents were used as provided. Flash chromatography was performed with Ultrapure silica gel or with RediSep R_f silica gel columns on a Teledyne ISCO CombiFlash Rf system using the solvents as indicated. Reverse-phase chromatography was performed with C18-bound silica gel. The general method for purification of these compounds involved the adjustment of the pH of aqueous TFA salt solutions to 8.0 using 28% aqueous ammonia, followed by evaporation. The residues were loaded on a C-18 bound silica gel cartridge, followed by elution with water. Relevant fractions were lyophilized to obtain the final compounds. Nuclear magnetic resonance (NMR) spectra were recorded on a Varian 600 MHz (Agilent Technologies, Santa Clara, CA) or Bruker 400 spectrometer (Bruker, Billerica, MA) with Me₄Si or signals from the residual solvent as the internal standard for ¹H and ¹³C. Chemical shifts are reported in ppm, and signals are described as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), brs (broad singlet), and dd (double doublet). Values given for coupling constants are first order. High-resolution and low-resolution mass spectra were recorded on an Agilent TOF II TOF/MS instrument equipped with an ESI interface. All compounds were >95% pure by HPLC analysis.

All reagents and solvents were obtained from commercial sources and used without further purification. Microwave reactions were performed in 10 or 35 mL microwave reaction vials using a CEM Discover S reactor. Column chromatography was performed using a Teledyne ISCO CombiFlash Rf system with prepacked silica cartridges or High Performance Gold C18 columns. ¹H/¹³C NMR spectra were recorded at ambient temperature on a 400 or 500 Varian FT-NMR instrument located in the Department of Chemistry and Biochemistry at the U.C. San Diego. Mass spectra were obtained from the Molecular Mass Spectrometry Facility (MMSF) in the Department of Chemistry and Biochemistry at the University of California, San Diego. The purity of all compounds used in assays was determined to be ≥95% by high performance liquid chromatography (HPLC) analysis (Table S1, Figure S5) using an Agilent 6230 Accurate-Mass LC-TOFMS from the MMSF at U.C. San Diego.