Fractionlynx system

Reagents purchased were used as received, unless otherwise noted. Purification of intermediates and final compounds was performed using silica gel chromatography using the Biotage® Isolera^™One flash purification system. When required, preparative HPLC was conducted for final compounds on Waters FractionLynx system using acetonitrile/water and 0.1% formic acid gradient and collected based on UV monitoring at 254 nm. LCMS analysis was performed using a Waters Alliance reverse phase HPLC (columns Waters SunFire C18 4.6 × 50 mm, 3.5 μm, or Waters SunFire C8 4.6 × 50 mm, 3.5 μm), using a multi-wavelength photodiode array detector from 210 nm to 600 nm and Waters Micromass ZQ detector (electrospray ionization). All compounds tested had a purity of > 95% as measured by LCMS. ¹H NMR spectra were obtained with Varian NMR systems, operating at either 400 or 500 MHz at room temperature, using solvents from Cambridge Isotope Laboratories. Chemical shifts (δ, ppm) are reported relative to the solvent peak (CDCl₃: 7.26 [¹H]; DMSO-d₆: 2.50 [¹H]; Acetone-d₆: 2.05; or CD₃OD: 3.31 [¹H]). Data for ¹H NMR spectra are reported as follows: chemical shift (ppm), multiplicity (s for singlet, d for doublet, t for triplet, dd for doublet of doublet, m for multiplet), coupling constant (Hz), and integration. Compounds obtained from GSK in-house library were not resynthesized unless otherwise noted.