Sodium Hydroxide → 4-(1-(8-(5,6-Dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ylcarbamoyl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 4-(1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ylcarbamoyl)benzoate (100 mg, 0.19 mmol) and sodium hydroxide (100 mg) in 1,4-dioxane (5 mL) and water (5 mL) was stirred at 40° C. for 2 h. The residue was concentrated to ˜5 mL in vacuo and adjusted pH=2 with 1M HCl. The crude mixture was concentrated and purified by prep-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; gradient conditions: 20% acetonitrile/80% water (0.1% TFA, v/v) initially, proceeding to 45% acetonitrile/55% water (0.1% TFA, v/v) in a linear fashion over 9 min) to give 4-(1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ylcarbamoyl)benzoic acid (9.5 mg, 10%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 10.29 (s, 1H), 8.80 (d, 1H, J=5.4 Hz), 8.13 (s, 1H), 8.00-7.92 (m, 5H), 7.51-7.40 (m, 2H), 6.98-6.92 (m, 2H), 4.58 (brs, 2H), 3.99 (s, 3H), 3.85 (s, 3H), 2.28-1.98 (m, 5H). LC-MS: [M+H]+, 504, tR=1.236 min, HPLC: 98.3% at 214 nm, 98.4% at 254 nm, tR=4.52 min.

Provenance & Evidence