Reaction Steps
To an ice cooled solution of piperidine-4-carboxylic acid [2-(2,4-dichlorophenoxy)phenyl]-amide (AMR01038, 100 mg, 0.274 mmol) in dry DCM (10 mL) were added pyridine (0.044 mL, 0.548 mmol) and benzoyl chloride (0.047 mL, 0.411 mmol). The reaction mixture was stirred at room temperature until TLC showed consumption of starting material (1 h), and quenched with saturated NaHCO3. The resulting solution was extracted with DCM (3×20 mL), and the combined organic layers were washed with water, 1M HCl (3×20 mL) and brine, dried (MgSO4), filtered and evaporated. Flash chromatography on silica gel of the crude product using hexane to EtOAc gradient as eluent gave 1-benzoylpiperidine-4-carboxylic acid [2-(2,4-dichloro-phenoxy)phenyl]amide (98 mg, 76%) as a white solid, mp 176-177° C. Rf: 0.17 (hexane/EtOAc 1:1) LC/MS (APCI) tr=1.10 min, m/z 471.26 (58), 469.31 (M++H, 100) HPLC tr=2.88 min (99.48%) 1H NMR (270 MHz, CDCl3) δ 1.85 (4H, m, 2CH2), 2.55 (1H, tt, CH), 3.01 (2H, m, CH2), 3.89 (1H, m, ½CH2), 4.74 (1H, m, ½CH2), 6.72 (1H, dd, J=8.2, 1.5 Hz, ArH), 6.95 (1H, d, J=8.6 Hz, ArH), 7.01 (1H, td, ArH), 7.14 (1H, td, ArH), 7.22 (1H, dd, J=8.6, 2.5 Hz, ArH), 7.39 (5H, s, ArH), 7.49 (1H, d, J=2.5 Hz, ArH), 7.78 (1H, br s, NH) and 8.38 (1H, br d, J=8.2, ArH). Anal. Calcd. for C25H22Cl2N2O3: C, 63.97; H, 4.72; N, 5.97. Found: C, 64.10; H, 4.83; N, 5.88%.
