反应详情

To a solution of (3R,4R)-tert-butyl 4-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-3-ethylpiperidine-1-carboxylate (350 mg, 0.750 mmol) in dichloromethane (3.8 ml) cooled to 0° C. was added trifluoroacetic acid (578 μl, 7.50 mmol). The reaction was allowed to warm to room temperature and stirring was continued for 1 hr. After removal of the solvent, the residue was taken into ethyl acetate, washed successively with saturated sodium bicarbonate, water, and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure, yielding 6-bromo-4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (275 mg, 0.75 mmol, 100% yield) as a yellow solid. LCMS (Method K) m/z 368.3 ([M+H]+). Analytical SFC conditions, Column: CC4 from ES Industries; Mobile phase: 10-50% MeOH (with 0.1% DEA) in CO2 in 8 min, 50% MeOH (with 0.1% DEA) in CO2 for 4 more min; Temperature: 40° C., Flow rate: 3 mL/min, BPR: 140 bars, Detection: UV (254 & 220 nm). Retention Time (min): 8.153 (>98.5% ee).

1. customAfter removal of the solvent
2. washwashed successively with saturated sodium bicarbonate, water, and brine
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure