reagents for each reaction were purchased from Sigma-Aldrich, Fluorochem, TCI, ABCR, Merck or Acros Organics and used without further purification. All reactions were carried out using anhydrous solvents. Preparative column chromatography was performed on Merck silica gel (0.063-0.200 mm, 60 Å) or using an automated flash column chromatography system puriFlash XS520Plus (Interchim, Montluçon, France). Thin-layer chromatography was carried out on Merck (Darmstadt, Germany) aluminum sheets, silica gel 60 F254. Detection was performed with UV light at 254 nm. Retention factors (Rf) are indicated. Melting points were determined on a Büchi (Essen, Germany) 510 oil bath apparatus. H NMR and 13 C NMR spectra were recorded on a Bruker Avance 400 MHz NMR spectrometer, Bruker Avance DRX 500 MHz NMR spectrometer or on a Bruker Avance III 600 MHz NMR spectrometer, respectively. NMR spectra were processed and analyzed in MestReNova. Chemical shifts are given in parts per million (ppm), coupling constants J are given in hertz (Hz), and standard abbreviations are used to indicate spin multiplicities. In case of rotamers, only the peaks for the major rotamer are given. Assignments were made based on one and two-dimensional NMR techniques, which include 1 H, 13 C, DEPT, HSQC, and HMBC experiments. LC-MS analyses were carried out on an API2000 (Applied Biosystems, Darmstadt, Germany) or an Expression CMSL (Advion, Ithaca, NY, USA) mass spectrometer coupled to an Agilent (Santa Clara, CA, USA) 1100 or 1260 Infinity II LC system. An EC50/2 Nucleodur C18 Gravity 3 μm column (Macherey-Nagel, Düren, Germany) or a XBridge BEH C18 3.5 µm column (Waters, Eschborn, Germany) was used. Samples (1 mg/mL) were dissolved in MeOH containing 2 mM ammonium acetate or MeOH. A volume of 8 µL or 10 µL was injected into the column at 25 °C or at 40 °C. Flow rate was 0.3 mL/min or 1.5 mL/min. Unless stated otherwise, the mobile phase was a gradient of 90% H2O to 100% MeOH containing 2 mM ammonium acetate in 10 min, then 100% MeOH containing 2 mM ammonium acetate to 20 min. For purity determination, diode array detection (DAD) was applied in the range of 220-400 nm. Positive total ion scans were observed from 150-800 m/z. High resolution mass spectrometry (HRMS) spectra were recorded on a Thermo Scientific Q Exactive Plus mass spectrometer (Thermo Fisher Scientific). LC-MS was used to determine the purity of the compounds. The area under the curve (AUC) of all peaks, except of the injection peak, were added and set to 100%. The purity of all the final compounds was confirmed to be ≥ 95%, as analyzed by LC-MS. cisVH298 was available from previous studies. Daprodustat was obtained from GSK (UK).