Trifluoroacetic acid → HCID 178501621, compound

Participants

Reaction Conditions

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 (50.0 mg, 0.092 mmol) and DIEA (0.064 mL, 0.367 mmol) in CH2Cl2 (1 mL) was added methyl 2-bromoacetate (21.07 mg, 0.138 mmol), and the reaction mixture was heated 45° C. in a seal-tube apparatus for 14 hrs. The reaction mixture was concentrated, treated with TFA (0.424 mL, 5.51 mmol) and heated at 65° C. for 1 hr. The reaction mixture was concentrated and diluted with methanol and purified using preparative 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, methyl N-(trans-4-((8-(cyclopropylamino)-3-((2-fluoro-4-pyridinyl)carbamoyl)imidazo[1,2-b]pyridazin-6-yl)amino)cyclohexyl)glycinate, as an off-white solid ((23 mg, 0.046 mmol, 50.5% 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=1.32 (M+H=497.3).

Provenance & Evidence