To a stirred solution of 5-(4-methylpiperazin-1-yl)picolinic acid (185 mg, 0.46 mmol) in 5 mL of DCM was added DIEA (82 μL, 0.46 mmol) and ethyl chloroformate (45 μL, 0.46 mmol). The resulting mixture was stirred at rt for 15 min, sonicated for 10 min. 1-(4-Aminophenyl)-3-(5-tert-butylisoxazol-3-yl)urea (128 mg, 0.46 mmol) was added. The resulting mixture was refluxed for 30 min. LC-MS indicated the reaction mostly done. Solvent was then removed under reduced pressure and residue was purified on reverse phase HPLC to give N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-5-(4-methylpiperazin-1-yl)picolinamide (65 mg, 29%) as a white foamy solid. LC-MS (ESI) m/z 478 (M+H)+. 1H NMR (300 MHz, DMSO-d6) δ 10.26 (s, 1H), 9.48 (s, 1H), 8.79 (s, 1H), 8.36 (d, J=2.45 Hz, 1H), 7.96 (d, J=8.85 Hz, 1H), 7.80 (d, J=8.85 Hz, 2H), 7.47 (dd, J=2.64, 8.85 Hz, 1H), 7.41 (d, J=9.04 Hz, 2H), 6.50 (s, 1H), 3.35 (br. s., 8H), 2.26 (s, 3H), 1.30 (s, 9H).
