Acetyl chloride → 8-(6-acetamido-4-chloropyridin-2-ylamino)-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

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Reaction Steps

To a solution of 4-chloropyridine-2,6-diamine (35.2 mg, 0.245 mmol) in THF (0.5 mL) was added 60% NaH (12.26 mg, 0.307 mmol). The mixture was stirred for 10 min. 5A (40 mg, 0.123 mmol) was added, followed by DMF (0.5 mL). The mixture was stirred at room temperature overnight. To the reaction mixture was added acetyl chloride (0.052 mL, 0.736 mmol) and a few drops of DIEA. The mixture was stirred at 65° C. for 20 min and then cooled to room temperature. Saturated NH4Cl was added and the resulting precipitate was collected by filtration, washed with water, and dried in vacuum to give crude 41A as a yellow solid (40 mg, 49%). HPLC Rt=3.283 min. (Chromolith SpeedROD 4.6×50 mm, 10-90% aqueous methanol containing 0.1% TFA, 4 min gradient, monitored at 220 nm), [M+H]=475.

Provenance & Evidence