Potassium Phosphate, Tribasic → 4-(((3R,4R)-3-ethyl-1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl)amino)-6-(1-isopropyl-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a vial charged with 6-bromo-4-(((3R,4R)-3-ethyl-1-(2-hydroxy-2-methylpropanoyl)-piperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (20 mg, 0.044 mmol), 1-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (20.88 mg, 0.088 mmol), and PdCl2(dppf)-CH2Cl2 Adduct (3.61 mg, 4.42 μmol) were added 1,4-dioxane (295 μl) and a 2M solution of potassium phosphate (66.3 μl, 0.133 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 with methanol (10 ml), filtered, and concentrated under reduced pressure. The crude product was purified via preparative HPLC (Column: Waters XBridge C18, 19×200 mm, 5-μm). The collected fractions were combined and dried via centrifugal evaporation, yielding 4-(((3R,4R)-3-ethyl-1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl)amino)-6-(1-isopropyl-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (14.6 mg, 0.030 mmol, 68.6% yield) as a white solid. 1H NMR (500 MHz, 1:1 Chloroform-d/Methanol-d4) δ 8.10 (s, 1H), 7.83 (s, 1H), 7.75-7.72 (m, 2H), 6.92 (d, J=1.5 Hz, 1H), 4.65-4.50 (m, 2H), 4.32 (s, 2H), 4.15 (br. s., 1H), 2.97 (d, J=12.4 Hz, 1H), 2.36 (d, J=11.4 Hz, 1H), 1.79 (br. s., 1H), 1.70-1.61 (m, 2H), 1.57 (d, J=6.4 Hz, 6H), 1.49 (s, 6H), 1.41-1.25 (m, 1H), 1.01 (t, J=7.4 Hz, 3H). HPLC (Method F) Rt: 1.966 min. LCMS (Method K) m/z 482.29 ([M+H]+).

Provenance & Evidence