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

Participants

Reaction Conditions

Reaction Steps

Compound 28c (867 mg, 2.99 mmol), 5-bromo-2-chloropyridine (888 mg, 4.48 mmol), Pd(OAc)2 (46.9 mg, 0.209 mmol), PPh3 (54.8 mg, 0.209 mmol), and KOAc (879 mg, 8.95 mmol) were placed in a 40 mL vial equipped with a stir bar and then the vial was evacuated and backflushed with argon. Dry DMA (10 mL) was added via syringe and then the mixture was heated to 110° C. and stirred for 16 h. The reaction was cooled to rt, diluted with EtOAc (30 mL), and filtered. The solids were washed with EtOAc (30 mL) and then the combined filtrates were washed with water (2×20 mL) and brine (20 mL). The organic phase was dried over Na2SO4 and filtered, and then the solvent was removed under reduced pressure. The crude product was chromatographed on a 40 g SiO2 pre-packed column eluting with 0-60% EtOAc/DCM to afford compound 28d. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.68 (d, J=2.2 Hz, 1H), 8.07 (dd, J=8.3, 2.4 Hz, 1H), 8.00 (d, J=5.6 Hz, 1H), 7.47 (d, J=8.3 Hz, 1H), 6.11 (d, J=5.6 Hz, 1H), 4.18 (q, J=7.2 Hz, 2H), 3.96-4.03 (m, 4H), 3.89-3.95 (m, 4H), 3.84 (s, 2H), 1.26 (t, J=7.1 Hz, 3H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C19H20ClN5O3: 402.1 (M+H). Found: 402.1.

Provenance & Evidence