2-Hydroxyisobutyric acid → Pyrrolo[1,2-b]pyridazine-3-carboxamide

To a solution of 6-bromo-4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (275 mg, 0.75 mmol) and 2-hydroxy-2-methylpropanoic acid (156 mg, 1.501 mmol) in dichloromethane (3.8 ml) were added DIEA (1.3 ml, 7.5 mmol) and HATU (571 mg, 1.501 mmol). The reaction was stirred at room temperature for 14 hrs. The product mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified via medium pressure chromatography (silica gel column, EtOAc/hexanes eluent, 0-100% gradient elution) to yield 6-bromo-4-((3R,4R)-3-ethyl-1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl)amino)pyrrolo-[1,2-b]pyridazine-3-carboxamide (240 mg, 0.531 mmol, 70.7% yield) as a white solid. LCMS (Method K) m/z 454.4 ([M+H]+).

1. customThe product mixture was partitioned between ethyl acetate and water
2. washThe ethyl acetate layer was washed with brine
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe crude product was purified via medium pressure chromatography (silica gel column, EtOAc/hexanes eluent, 0-100% gradient elution)

ORD record

ord-e3e0591ba9d748b7810b24c9b44bac36

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987268B2