HCID 11518123, compound → HCID 58335761, compound

Participants

Reaction Conditions

Reaction Steps

In step 15-1, 2-(2-methyl-1,3-dioxolan-2-yl)-6-(tributylstannyl)pyridine (57 g, 124 mmol) in 100 mL of toluene was cannula transferred under the argon atmosphere to a suspension of 3-bromo-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (15-1) (30 g, 83 mmol) and tetrakis(triphenylphospine)palladium (4.8 mg, 4.15 mmol) in 500 mL of toluene. The resulting reaction mixture was heated to 110° C. for overnight. The reaction progress was monitored by LC/Mass. After the reaction was complete, the reaction vessel was cooled to room temperature and the solvent reduced to ⅓ of the original volume. The purification was performed by flash chromatography using pure ethyl acetate to afford (R)-6-(2-(3-fluorophenyl)pyrrolidin-1-yl)-3-(6-(2-methyl-1,3-dioxolan-2-yl)pyridine-2-yl)imidazo[1,2-b]pyridazine (15-2). 1H NMR (400 MHz, DMSO-d6) δ 8.10 (s, 1H), 8.09 (s br, 1H), 7.93 (d, 1H, J=9.6 Hz), 7.72 (m, 1H), 7.39 (m, 2H), 7.18 (m, 2H), 7.04 (m, 1H), 6.89 (br s, 1H), 5.16 (d, 1H, J=8.0 Hz), 4.02 (m, 3H), 3.91 (m, 2H), 3.68 (m, 2H), 2.48 (m, 1H), 2.05 (m, 2H), 1.88 (m, 1H), 1.69 (s, 3H). LCMS: m/z 446.2 (M+1).

Provenance & Evidence