18087-73-5

3-Bromoimidazo[1,2-B]pyridazine is a pharmaceutical intermediate compound. It is used in the preparation of Ponatinib, a tyrosine kinase inhibitor (TKI), which is used in the treatment of chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL).

Imidazo[1,2-b]pyridazine (6.0 g, 50.4 mmol) was used as starting material, and N-bromosuccinimide (NBS, 6.0 g, 75.6 mmol) and a catalytic amount of azobisisobutyronitrile (AIBN) were added in 50 mL of chloroform. The reaction mixture was heated and refluxed for 2 h, during which the progress of the reaction was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the mixture was cooled to room temperature and subsequently stirred under ice bath conditions to promote precipitation. The precipitate was separated by filtration and the filtrate was concentrated to afford the target product 3-bromoimidazo[1,2-b]pyridazine as a pale yellow solid in 75% yield.

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[2] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 23, p. 5830 - 5835
[3] Patent: EP2818471, 2014, A1. Location in patent: Paragraph 0122; 0123
[4] Synthesis, 1981, # 12, p. 987 - 989
[5] Patent: WO2016/210036, 2016, A1. Location in patent: Page/Page column 107