Trifluoroacetic acid → HCID 178486185, compound

Participants

Reaction Steps

To a solution of 6-((trans)-4-aminocyclohexylamino)-8-(cyclopropyl(4-methoxybenzyl)amino)-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide 8B (30 mg, 0.055 mmol) in CH2Cl2 (1 mL) was added DIEA (0.0062 mL, 0.035 mmol) and dimethylsulfamoyl chloride (1.5 mg, 10.45 μmol). The reaction mixture was stirred at room temperature for 2 hrs, concentrated, re-dissolved in TFA (0.849 mL, 11.02 mmol) and heated at 70° C. for 1 hr. The reaction mixture was concentrated and purified by HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 30% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 100% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA)) to isolate the title compound, 8-(cyclopropylamino)-6-((trans-4-((dimethylsulfamoyl)amino)cyclohexyl)amino)-N-(3-fluoro-4-pyridinyl)imidazo[1,2-b]pyridazine-3-carboxamide, as a white solid (13.0 mg, 44.4%). 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=1.61 (M+H=532.26). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.39 (1H, s), 8.71 (1H, d, J=2.52 Hz), 8.49 (1H, t, J=6.17 Hz), 8.43 (1H, d, J=5.29 Hz), 8.00 (1H, s), 7.61 (1H, s), 7.28 (1H, d, J=8.06 Hz), 6.92 (1H, d, J=8.31 Hz), 5.98 (1H, s), 3.78 (1H, br. s.), 3.00 (2H, br. s.), 2.58-2.73 (6H, m), 2.01 (2H, br. s.), 1.90 (2H, br. s.), 1.26 (4H, d, J=13.09 Hz), 0.68-0.85 (2H, m), 0.51-0.69 (2H, m).

Provenance & Evidence