Diisopropylethylamine → 4-(((3R,4R)-3-ethyl-1-((S)-2-hydroxybutanoyl)piperidin-4-yl)amino)-6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide

Participants

Reaction Steps

To a solution of (S)-2-hydroxybutanoic acid (3.54 mg, 0.034 mmol) in DMF (181 μl) were added DIEA (28.5 μl, 0.163 mmol) and HATU (25.9 mg, 0.068 mmol). After 15 minutes, 4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)-6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (10 mg, 0.027 mmol) was added. The reaction was stirred at room temperature for 3 hrs. The product mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried with sodium sulfate, 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 to yield the title compound (7.9 mg, 0.017 mmol, 64.0% yield) as a white solid. 1H NMR (500 MHz, 1:1 Chloroform-d/Methanol-d4) δ 8.12-8.09 (m, 1H), 7.77 (d, J=2.5 Hz, 1H), 7.72 (d, J=3.5 Hz, 2H), 6.92-6.88 (m, 1H), 4.42-4.34 (m, 2H), 4.24-4.13 (m, 1H), 3.95 (s, 3H), 3.12-3.03 (m, 1H), 2.41-2.34 (m, 1H), 1.84-1.73 (m, 2H), 1.70-1.58 (m, 3H), 1.43-1.32 (m, 1H), 1.06-0.97 (m, 7H). LCMS (Method K) m/z 454.249 ([M+H]+). HPLC (Method F) Rt: 1.12 min.

Provenance & Evidence