Acetic Acid → HCID 86670393, compound

Participants

Reaction Steps

Using a new 10% Pd/C CatCart cartridge (30 mm), a H-Cube/Gilson (Thalesnano Technology, Budapest, Hungary) system was purged with 1:1 0.5 M AcOH in EtOAc:EtOH. The CatCart was pre-saturated with H2 for 10 min (using the pre-saturate setting in the autosampler software program) at 0.5 mL/min. A solution of ((S)-1,1,1,3,3,3-hexafluoro-2-(2-(2-methyl-4-(2-nitrophenylsulfonyl)piperazin-1-yl)pyrimidin-5-yl)-2-propanol (0.21 g, 0.40 mmol) in 4.0 mL 1:1 0.5 M AcOH in EtOAc:EtOH was prepared. Three injections set at 1.5 mL were made, 30 mm 10% Pd/C CatCart, flow rate 0.5 mL/min, “1 bar” i.e., setting at “Full H2” on H-cube; temp 40° C.; 10 mL volume collected for each injection. The collected solution was concentrated and then dissolved in CH2Cl2. The solution was treated with saturated aqueous sodium bicarbonate then passed through a phase separation cartridge (Radleys Discovery Technologies, Essex, UK) dried (Na2SO4), and then concentrated. The residue was then purification by silica gel chromatography (0 to 70% EtOAc/hexane) to afford (S)-2-(2-(4-(2-aminophenylsulfonyl)-2-methylpiperazin-1-yl)pyrimidin-5-yl)-1,1,1,3,3,3-hexafluoro-2-propanol (92 mg) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.87 (s, 1H), 8.53 (s, 2H), 7.40 (dd, J=1.4, 8.2 Hz, 1H), 7.25-7.34 (m, 1H), 6.85 (d, J=7.8 Hz, 1H), 6.63 (t, J=7.1 Hz, 1H), 6.06 (s, 2H), 4.94 (br s, 1H), 4.57 (d, J=13.7 Hz, 1H), 3.75 (d, J=11.5 Hz, 1H), 3.51 (d, J=11.9 Hz, 1H), 3.10-3.27 (m, 1H), 2.60 (dd, J=3.7, 11.9 Hz, 1H), 2.38-2.47 (m, 1H), 1.10-1.22 (m, 3H). m/z (ESI, +ve ion) 499.9 (M+H)+. GK-GKRP IC50 (Binding)=0.508 μM; GK-GKRP EC50 (LC MS/MS-2)=0.516 μM.

Provenance & Evidence