Potassium Phosphate, Tribasic → (R)-tert-butyl 4-((7-carbamoyl-2-(1-ethyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-8-yl)amino)-3,3-dimethylpiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a reaction vial charged with (R)-tert-butyl 4-((2-bromo-7-carbamoylimidazo[1,2-b]pyridazin-8-yl)amino)-3,3-dimethylpiperidine-1-carboxylate (69.1 mg, 0.148 mmol), 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (65.7 mg, 0.296 mmol), and PdCl2(dppf)-CH2Cl2 Adduct (12.07 mg, 0.015 mmol) in dioxane (986 μl) was added potassium phosphate, dibasic (222 μl, 0.444 mmol). The suspension was purged with nitrogen for 5 minutes. The vial was sealed and heated at 100° C. for 2 hrs. The reaction was diluted methanol (10 ml), filtered, and concentrated. The resulting brown oil was partitioned between ethyl acetate and water. The organic layer was washed with water and brine, dried with sodium sulfate, filtered, and concentrated to give an oil. The oil was purified via flash chromatography (ISCO silica gel column, 0-100% EtOAc/hexanes) to afford (R)-tert-butyl 4-((7-carbamoyl-2-(1-ethyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-8-yl)amino)-3,3-dimethylpiperidine-1-carboxylate (62.2 mg, 0.129 mmol, 87% yield) as a white solid. ESI-MS (analytical LCMS Method B): m/z 483.1 ([M+H]+). HPLC (analytical HPLC Method B) Rt: 3.345 min

Provenance & Evidence