Triphenylphosphine → Ethyl 3-(6-chloropyridin-3-yl)-8-morpholinoimidazo[1,2-b]pyridazine-2-carboxylate

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Reaction Conditions

Reaction Steps

Compound 5c, 5-bromo-2-chloropyridine (12.7 g, 64.1 mmol), Pd(OAc)2 (671 mg, 2.99 mmol), PPh3 (784 mg, 2.99 mmol), and KOAc (12.6 g, 128 mmol) were placed in a 250 mL pressure vessel equipped with a stir bar and then the flask was flushed with Argon. Dry DMA (150 mL) was added and then the vessel was capped under an argon purge. The reaction was stirred at 110° C. for 8 h. The reaction was cooled to rt, diluted with water (300 mL), and filtered. The precipitate was washed with water (2×200 mL), and then the solid was dissolved in DCM (500 mL). To this solution was added 50 g SiO2 and the solvent was removed under reduced pressure. The material was dry-loaded onto a 240 g SiO2 pre-packed column and eluted with 0-60% EtOAc/DCM. The fractions containing the product were pooled and concentrated to afford a residue that was triturated with EtOAc. The solid was isolated by filtration, washed with EtOAc (2×50 mL), and then dried under reduced pressure to afford compound 20a. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.65 (d, J=2.0 Hz, 1H), 8.04 (d, J=5.9 Hz, 1H), 7.97 (dd, J=8.2, 2.3 Hz, 1H), 7.47 (d, J=8.3 Hz, 1H), 6.14 (d, J=5.9 Hz, 1H), 4.34 (q, J=7.1 Hz, 2H), 4.01-4.11 (m, 4H), 3.90-3.99 (m, 4H), 1.29 (t, J=7.1 Hz, 3H).

Provenance & Evidence