4-Aminopyridine → 8-Bromo-6-chloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

関与物質

反応条件

反応手順

To a 2 dram vial was added a mixture of 8-bromo-6-chloroimidazo[1,2-b]pyridazine-3-carboxylic acid and 6,8-dichloroimidazo[1,2-b]pyridazine-3-carboxylic acid (250 mg, 1.077 mmol), and oxalyl chloride (1.077 mL, 2.155 mmol) in dichloromethane (2 mL). The solution was stirred at 25° C. for 1 hour. The solvent and excess oxalyl chloride were removed in vacuo. The residue was dissolved in dichloromethane (2 mL), and triethylamine (0.451 mL, 3.23 mmol), pyridin-4-amine (152 mg, 1.616 mmol), and 2 crystals of DMAP were added. The reaction solution was stirred at 25° C. for 6 hours. The solution was quenched with dichloromethane, washed 2× with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give a mixture of 6,8-dichloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide and 8-bromo-6-chloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (202 mg, 0.656 mmol, 60.8% yield). LC/MS, m/z 307.93 (M+1). HPLC Rt, 1.49 min. Waters Sunfire C18 column (4.6×50 mm) 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

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