Water → HCID 68291100, compound

Participants

Reaction Steps

To a solution of methyl 3-(6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-ylamino)-2,2-dimethylbutanoate (1.0 g, 2.61 mmol) in toluene (10 ml) was added phenyl boronic acid (0.44 g, 3.91 mmol) and stirred for 10 minutes at RT. Sodium carbonate (0.553 gm, 5.22 mmol), Pd(dppf)2 (0.10 gm, 3.91 mmol), water (2.0 ml) and tetrabutyl ammonium hydroxide (1 drop) was added at room temperature under nitrogen atmosphere and the reaction mixture was degassed with nitrogen for 15 minutes. The reaction mixture was stirred at 110° C. in a CEM microwave synthesizer for 8 hours. Upon completion, the reaction mixture was cooled to room temperature and the layers were separated. The aqueous layer was washed with ethyl acetate (3×50 ml). The combined organic layers were washed with brine (25 ml), dried over anhyd. sodium sulfate, filtered and concentrated under vacuum. The crude compound was purified by column chromatography using 30% ethyl acetate in hexanes as the eluting solvent to give the title compound (600 mg, 60%). 1H NMR (400 MHz, DMSO-d6): δ 1.32-1.34 (m, 6H), 1.37-1.39 (m, 3H), 3.73 (s, 3H), 4.68-4.70 (m, 1H), 7.157-7.161 (d, J=1.6 Hz, 1H), 7.27-7.31 (m, 1H), 7.41-7.44 (m, 2H), 7.62-7.65 (m, 2H), 7.87-7.88 (m, 2H). 10.60-10.63 (d, J=10 Hz, 1H).

Provenance & Evidence