Trifluoroacetic acid → HCID 178462171, compound

Participants

Reaction Steps

BOP (129 mg, 0.292 mmol) was added to a solution of 6-((trans)-4-aminocyclohexylamino)-N-(6-(benzyloxy)pyrimidin-4-yl)-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carboxamide (50.0 mg, 0.097 mmol), DIEA (0.068 mL, 0.39 mmol) and (R)-2-(tert-butoxycarbonylamino)propanoic acid (36.8 mg, 0.195 mmol) in DCM (1 mL). The clear reaction mixture was stirred at room temperature for 30 min and concentrated. TFA (0.450 mL, 5.84 mmol) was added, and the reaction mixture was heated at 70° C. for 1 hr. The reaction mixture was diluted in methanol and purified with HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 10% 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, 6-((trans-4-(D-alanylamino)cyclohexyl)amino)-8-(cyclopropylamino)-N-(6-oxo-1,6-dihydro-4-pyrimidinyl)imidazo[1,2-b]pyridazine-3-carboxamide, as a white solid (26 mg, 0.053 mmol, 54.0% yield). 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=1.393 (M+H=495.16).). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.56 (1H, br. s.), 11.73 (1H, s), 8.29 (1H, d, J=7.78 Hz), 8.18 (1H, s), 8.06 (3H, d, J=4.27 Hz), 7.90-8.00 (1H, m), 7.61 (1H, s), 7.05 (1H, s), 7.00 (1H, d, J=7.78 Hz), 5.96 (1H, s), 3.68-3.92 (2H, m), 3.46-3.69 (1H, m), 2.10 (2H, d, J=10.54 Hz), 1.82 (2H, d, J=2.51 Hz), 1.43-1.69 (2H, m), 1.16-1.43 (5H, m), 0.69-0.86 (2H, m), 0.51-0.70 (2H, m).

Provenance & Evidence