Acetone → HCID 54761506, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of N-(4-(3-(5-(1,3-difluoro-2-methylpropan-2-yl)isoxazol-3-yl)ureido)phenyl)-5-(piperidin-4-yloxy)picolinamide hydrochloride (50 mg, 0.091 mmol) from Step 4 of Example 17 (65 mg, 0.12 mmol) in 2 mL of pH˜4 MeOH/NaOAc buffer was added acetone (0.3 mL, excess) and NaCNBH3 (25 mg, excess). The resulting mixture was reflux at 80° C. for 3 h. LC-MS indicated that the reaction was 50% complete. The reaction was cooled to rt and the crude product was purified by reverse phase HPLC to give N-(4-(3-(5-(1,3-difluoro-2-methylpropan-2-yl)isoxazol-3-yl)ureido)phenyl)-5-(1-isopropylpiperidin-4-yloxy)picolinamide as a white solid (20 mg, 31% yield). LC-MS (ESI) m/z 557 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 10.38 (s, 1H), 9.83 (br. s., 1H), 9.03 (br. s., 1H), 8.35 (d, J=2.83 Hz, 1H), 8.08 (d, J=8.67 Hz, 1H), 7.81 (d, J=9.04 Hz, 2H), 7.65 (dd, J=2.73, 8.76 Hz, 1H), 7.43 (d, J=9.04 Hz, 2H), 6.79 (s, 1H), 4.73 (s, 2H), 4.57 (s, 3H), 2.73 (d, J=6.40 Hz, 3H), 2.23-2.45 (m, 2H), 1.99 (br. s., 2H), 1.53-1.73 (m, 2H), 1.34 (s, 3H), 0.98 (d, J=6.59 Hz, 6H).

Provenance & Evidence