Potassium Phosphate, Tribasic → HCID 89995644, compound

Participants

Reaction Conditions

Reaction Steps

To a reaction vial charged with (3S,4S)-tert-butyl 3-((2-bromo-7-carbamoylimidazo[1,2-b]pyridazin-8-yl)amino)-4-methylpyrrolidine-1-carboxylate (from Step 3 of Example 1, 300 mg, 0.683 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (426 mg, 2.049 mmol) and PdCl2(dppf)-CH2Cl2 Adduct (55.8 mg, 0.068 mmol) were added dioxane (4.553 ml) and potassium phosphate, tribasic (1024 μl, 2.049 mmol). The suspension was purged with nitrogen for 5 minutes. The vial was sealed and heated at 90° C. for 1 hr. The reaction mixture was diluted with methanol (10 ml), filtered, and concentrated under reduced pressure, yielding a dark oil. The oil was partitioned between ethyl acetate and water. The organic layer was washed with (sat.) sodium chloride, dried with sodium sulfate, filtered and concentrated under reduced pressure to give an oil. The crude oil was purified via flash chromatography (ISCO silica gel column, 0-10% DCM-MeOH eluents) to give (3S,4S)-tert-butyl 3-((7-carbamoyl-2-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-8-yl)amino)-4-methylpyrrolidine-1-carboxylate as a yellow solid. 1H NMR (400 MHz, methanol-d4) δ 8.33 (s, 1H), 8.03-7.95 (m, 2H), 7.86 (s, 1H), 6.07-5.86 (m, 1H), 3.93 (s, 3H), 3.85-3.73 (m, 1H), 3.72-3.62 (m, 1H), 3.57-3.45 (m, 1H), 3.23-3.14 (m, 1H), 2.67 (d, J=4.8 Hz, 1H), 1.46 (d, J=13.0 Hz, 9H), 1.16-1.06 (m, 3H). ESI-MS (analytical LCMS Method B): m/z 441.3 ([M+H]+). HPLC (analytical HPLC Method B) Rt: 3.123 min.

Provenance & Evidence