反应详情

To a solution of 6-bromo-4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide from Step 2 of Example 125 (150 mg, 0.410 mmol) and DIEA (429 μl, 2.457 mmol) in DMF (2.7 ml) was added methanesulfonyl chloride (47.5 μl, 0.614 mmol). The reaction was stirred at room temperature for 2 hrs. After removal of the solvent, the residue was dissolved in ethyl acetate, washed successively with saturated ammonium chloride, water, and brine; dried with 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-(methylsulfonyl)piperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (95 mg, 0.214 mmol, 52.2% yield) as a yellow solid. LCMS (Method K) m/z 446.0 ([M+H]+).

1. customAfter removal of the solvent
2. dissolutionthe residue was dissolved in ethyl acetate
3. washwashed successively with saturated ammonium chloride, water, and brine
4. dry with materialdried with sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe crude product was purified via medium pressure chromatography (silica gel column, EtOAc/hexanes eluent, 0-100% gradient elution)