Sodium Hydroxide → 5-(2-Amino-6-(6-chloro-5-(methylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzoic acid

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Reaction Steps

Following the procedure described for N-(5-(2-amino-3-(3-fluorophenyl)imidazo[1,2-b]pyridazin-6-yl)-2-chloropyridin-3-yl)methanesulfonamide (Example 23), N-(6-(6-chloro-5-(methylsulfonamido)pyridin-3-yl)-3-(4-fluoro-3-(morpholine-4-carbonyl)phenyl)imidazo[1,2-b]pyridazin-2-yl)acetamide (TFA salt) (Example 24) (0.016 g, 0.023 mmol) was treated with sodium hydroxide (0.100 mL, 1.0 mmol, 10 M) and purified by preparative HPLC (Phenomenex Gemini 5 micron (Phenomenex, Torrance, Calif.), C18, 100×30 mm, 5 to 85% CH3CN(0.1% TFA)/H2O(0.1% TFA) over 20 min then 100% CH3CN(0.1% TFA) for 3 minutes at 20 mL/min) with the fractions containing suspected product concentrated to afford the title compound as a yellow solid (3.6 mg, 27%). MS (ESI, positive ion) m/z: 477 (M−TFA+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.19 (s, 3H), 6.00 (br s, 2H), 7.40-7.45 (m, 1H), 7.77 (d, J=9.2 Hz, 1H), 7.91 (d, J=9.2 Hz, 1H), 8.23-8.28 (m, 1H), 8.45 (d, J=2.0 Hz, 1H), 8.47-8.50 (m, 1H), 8.93 (d, J=2.0 Hz, 1H), 9.85 (s, 1H), 13.28 (br s, 1H).

Provenance & Evidence