反应详情

A solution of (3S,4S)-benzyl 3-amino-4-(fluoromethyl)pyrrolidine-1-carboxylate, TFA (468 mg, 1.278 mmol) and 2-bromo-8-chloroimidazo[1,2-b]pyridazine-7-carboxamide (352 mg, 1.278 mmol), DIEA (1116 μl, 6.39 mmol) in DMA (5110 μl) was heated at 80° C. for 7 hrs. The reaction mixture was partitioned between ethyl acetate and water. The ethyl acetate solution was washed with saturated NaCl, dried with sodium sulfate, filtered, and concentrated to yield a brown oil. The crude product was purified by flash column (ISCO 12 g, 0-100% EtOAc/hexane) to afford (3S,4S)-benzyl 3-((2-bromo-7-carbamoylimidazo[1,2-b]pyridazin-8-yl)amino)-4-(fluoromethyl)pyrrolidine-1-carboxylate (615.6 mg, 1.253 mmol, 98% yield) as a faint yellow solid. ESI-MS (analytical LCMS Method B): m/z 493.2 ([M+H]+). HPLC (analytical HPLC Method B) Rt: 3.148 min.

1. customThe reaction mixture was partitioned between ethyl acetate and water
2. washThe ethyl acetate solution was washed with saturated NaCl
3. dry with materialdried with sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customto yield a brown oil
7. customThe crude product was purified by flash column (ISCO 12 g, 0-100% EtOAc/hexane)