Potassium Phosphate, Tribasic → 3-Bromo-6-chloro-8-(4-methylpyridin-3-yl)imidazo[1,2-b]pyridazine

Beteiligte Stoffe

Reaktionsschritte

A microwave vial was charged with a mixture of 3,8-dibromo-6-chloroimidazo[1,2-b]pyridazine (1.0 g, 3.21 mmol), 4-methylpyridin-3-ylboronic acid (0.440 g, 3.21 mmol), tetrakis(triphenylphosphine)palladium(0) (0.371 g, 0.321 mmol), dioxane (16 mL), and K3PO4 (4.82 mL, 9.64 mmol) (2.0 M solution in water) was stirred at room temperature for 5 min. under nitrogen. The resulting mixture was heated to 100° C. for 4 h in a microwave heater. The reaction mixture was cooled to room temperature, quenched with water, and diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by BIOTAGE® (20-80% EtOAc/CH2Cl2, 1.5 L, then 20%-65% B/CH2Cl2 (0.9 L); B: 10% MeOH/CH2Cl2) to give 320 mg (15.4%) product. 1H NMR (400 MHz, CD3OD) δ ppm 8.91 (1H, s), 8.82 (1H, d, J=5.79 Hz), 8.04 (1H, d, J=5.79 Hz), 7.88 (1H, s), 7.57 (1H, s), 2.54 (3H, s). LC (Conditions B & C): >95% purity; LC/MS: Rt=1.47 min. LC/MS (Condition A): 322.96/324.96.

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