Potassium Phosphate, Tribasic → (S)-4-(4,4-dimethylpyrrolidin-3-ylamino)-6-(2-methoxypyridin-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of benzyl 4-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-3,3-dimethylpyrrolidine-1-carboxylate (35 mg, 0.072 mmol) in 1,4-dioxane (0.3 mL), was added (2-methoxypyridin-4-yl)boronic acid (14.3 mg, 0.094 mmol), X-Phos (3.43 mg, 7.2 μmol) and potassium phosphate (2 M, 0.115 mL, 0.23 mmol). The reaction vial was purged with nitrogen, sealed and heated at 100° C. for 18 h. The reaction was diluted with ethyl acetate (50 mL), washed with aq. sodium bicarbonate and brine. The organic layer was dried and concentrated. The residue was suspended in acetonitrile (5 mL), was added iodotrimethylsilane (36.0 mg, 0.180 mmol) at 0° C., stirred at rt for 1 h. To the suspension was added ether (30 mL), stirred for additional 2 h, filtered and rinsed the collected solid with ether and dried to give the hydroiodide salt of the title compound (15 mg, 0.030 mmol, 41.0% yield) as a yellow solid. 1H NMR (500 MHz, METHANOL-d4) δ 8.15 (s, 1H), 8.09 (d, J=5.4 Hz, 1H), 8.01 (d, J=1.5 Hz, 1H), 7.58 (s, 3H), 7.31 (d, J=1.5 Hz, 1H), 7.25 (dd, J=5.4, 1.5 Hz, 1H), 7.09 (d, J=1.0 Hz, 1H), 4.61-4.54 (m, 1H), 4.30 (br. s., 1H), 3.94 (s, 3H), 3.73 (dd, J=11.9, 6.9 Hz, 1H), 3.12-3.04 (m, 2H), 1.97 (s, 2H), 1.24 (d, J=14.4 Hz, 6H), MS (ES+) m/z: 380.2, 381.3 (M+H); LC retention time: 0.84 min (analytical HPLC Method I).

Provenance & Evidence