Trifluoroacetic acid → HCID 178474200, compound

Participants

Reaction Steps

To N-(3-aminophenyl)acetamide (4.09 mg, 0.027 mmol), 83C (10 mg, 0.018 mmol) and DIEA in DMF (0.5 mL) was added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (16.06 mg, 0.036 mmol) and the reaction was stirred at room temperature overnight. One mL of TFA was added to the reaction mixture and heated at 60° C. After 1 hr, the reaction mixture was concentrated under reduced pressure and purified using preparative HPLC containing TFA to isolate N-(3-acetamidophenyl)-6-((trans)-4-aminocyclohexylamino)-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carboxamide (4 mg, 5.02 μmol, 27.6% yield) as a white solid. LC/MS (Phenomenex Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2 min with 1 min hold time, Flow rate=5 mL/min, detection at 254 nm, Solvent A: 10% methanol/90% water/0.1% TFA; Solvent B: 10% water/90% methanol/0.1% TFA) Rt=1.3 minutes. [M+H]=463.23. 1H NMR (500 MHz, METHANOL-d3) δ ppm 10.99 (1H, s), 7.92 (1H, d, J=1.83 Hz), 7.62 (1H, d, J=8.25 Hz), 7.37 (2H, t, J=8.25 Hz), 7.16 (1H, d, J=8.25 Hz), 6.08 (1H, s), 3.80 (1H, t, J=4.35 Hz), 3.09-3.26 (1H, m), 2.51-2.72 (1H, m, J=6.76, 6.76, 3.67, 3.44 Hz), 2.35 (2H, d, J=10.08 Hz), 2.11-2.24 (3H, m), 1.98-2.14 (2H, m), 1.67-1.89 (2H, m, J=12.72, 12.43, 12.43, 3.21 Hz), 1.37-1.53 (2H, m), 1.20-1.38 (1H, m), 0.82-1.00 (2H, m), 0.58-0.76 (2H, m).

Provenance & Evidence