Reaction Steps
Piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (HVB01062, 1.19 g, 5.2 mmol) was dissolved in anhydrous DCM (40 ml), and stirred under nitrogen. To this was added N N-4-dimethylaminopyridine (cat.), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.0 g, 4.2 mmol) and TEA (0.84 ml). Stirred for 30 min. 2-(4-Trifluoromethoxy-phenoxy)-phenylamine (HVB01053, 1.4 g, 5.2 mmol) was added and stirred under nitrogen for 20 h. Diluted with DCM, washed with HCl (1M, 20 ml), Sodium hydrogen carbonate (sat. 20 ml), and brine (20 ml). Organic layers combined and dried over anhydrous magnesium sulphate, and evaporated in-vacuo. The crude mixture was purified using flash chromatography (DCM/hexane, 0 to 100%), to afford a yellow solid, 1.59 g, 57%. m.p. 45-48° C., Rf. 0.65 (DCM), 1HNMR: (CDCl3, 270 MHz) δ 1.44 (9H, s, CH3), 1.67 (2H, td, J=13.4, 4.4 Hz, CH2), 1.80 (2H, dd, J=1.8 Hz, CH2), 2.36 (1H, m, CH), 2.74 (2H, t, J=11.9 Hz, CH2N), 4.12 (2H, d, J=11.6 Hz, CH2N), 6.85 (1H, dd, J=6.7, 1.5 Hz, Ar HD), 7.03 (2H, d, Ar HF), 7.04 (1H, m, Ar HB), 7.13 (1H, td, J=1.5, 6.4 Hz, Ar HC), 7.20 (2H, d, J=1.5, 6.4 Hz Ar HF), 7.64 (1H, s, NH), 8.40 (1H, d, J=8.2 Hz, Ar HA.
