Trifluoroacetic acid → HCID 86631967, compound

Participants

Reaction Steps

A sealable vial was charged with tert-butyl 4-(2-acetamido-6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate (104.0 mg, 151 μmol) and neat trifluoroacetic acid (1.16 mL, 15.1 mmol). The solution was stirred at rt for 1 h. The solution was then concentrated to give N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)-3-(1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide, which was of sufficient purity for further use. Methanol (2.0 mL) was added to the crude residue followed by an aqueous solution of sodium hydroxide (6 N, 502 μl, 3014 μmol). The solution was heated at 50° for 18 h. The solution was concentrated, then taken up in minimal MeOH/DMSO and purified by preparative HPLC (Gilson GX-218, Middletown, Wis.: 5-90% (0.1% TFA in CH3CN) in H2O over 15 min, Phenomenex, Zorbax 00F-4435-UO 150×30 mm, 5 micron) to afford the title compound, N-(5-(2-amino-3-(1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-b]pyridazin-6-yl)-2-chloropyridin-3-yl)-3-(difluoromethoxy)benzenesulfonamide (8.6 mg, 8.6% yield) as a yellow solid. LCMS (ESI positive ionization) m/z: 548.1 (M+1); 1H NMR (400 MHz, MeOH) δ ppm 3.12-3.23 (m, 2H); 3.59 (t, J=5.97 Hz, 2H); 3.97-4.08 (m, 2H); 6.35-6.48 (m, 1H); 6.84 (t, J=73.02 Hz, 1H); 7.40-7.46 (m, 1H); 7.49-7.66 (m, 3H); 7.87-7.94 (m, 1H); 7.97-8.04 (m, 1H); 8.79 (dd, J=15.55, 2.25 Hz, 2H).

Provenance & Evidence