Trifluoroacetic acid → (3S,4S)-benzyl 3-((2-bromo-7-carbamoylimidazo[1,2-b]pyridazin-8-yl)amino)-4-(fluoromethyl)pyrrolidine-1-carboxylate

Participants

Reaction Steps

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.

Provenance & Evidence