Acetaldehyde → HCID 54760985, compound

Participants

Reaction Steps

To a stirred solution of N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-4-(piperidin-4-yloxy)picolinamide hydrochloride from Example 1 (100 mg, 0.19 mmol) in 2 mL of pH˜4 MeOH/NaOAc buffer (21 grams of NaOAc.3H2O and 48 mL of AcOH, diluted to 1.0 L with methanol) was added acetaldehyde (0.2 mL, excess) and NaCNBH3 (25 mg, excess). The resulting mixture was stirred at rt for 3 h. LC-MS indicated that the reaction was complete. The crude product was purified by reverse phase HPLC to afford N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-4-(1-ethylpiperidin-4-yloxy)picolinamide as a white powder (52 mg, 53% yield). LC-MS (ESI) m/z 507 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 10.55 (s, 1H), 9.49 (s, 1H), 8.79 (s, 1H), 8.54 (d, J=5.65 Hz, 1H), 7.83 (d, J=9.04 Hz, 2H), 7.67 (br. s., 1H), 7.43 (d, J=8.85 Hz, 2H), 7.26 (dd, J=2.45, 5.65 Hz, 1H), 6.50 (s, 1H), 4.82 (br. s., 1H), 2.75-3.14 (m, 3H), 2.07 (br. s., 2H), 1.75 (br. s., 2H), 1.30 (s, 9H), 1.13 (br. s., 3H).

Provenance & Evidence