Potassium Carbonate → tert-Butyl 4-(5-(2-(2-ethoxy-2-oxoethyl)-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Compound 28d (854 mg, 2.13 mmol), K2CO3 (323 mg, 2.34 mmol), Cu powder (27.0 mg, 0.425 mmol), and 1-(tert-butoxycarbonyl)piperazine (435 mg, 2.34 mmol) were placed in a 40 mL vial equipped with a stir bar. The vessel was evacuated and backflushed with argon and then dry DMF (4 mL) was added via syringe. The reaction was heated to 130° C. and stirred for 3 d. The solvent was removed under reduced pressure and then the residue was partitioned between water (50 mL) and DCM (70 mL). The organic phase was separated and then the aqueous layer was extracted with DCM (2×20 mL). The organic extracts were combined and washed with brine (2×30 mL), and then dried over Na2SO4 and filtered. The solvent was removed under reduced pressure. The crude product was chromatographed on a 40 g SiO2 pre-packed column eluting with 0-80% ACN/DCM to afford compound 28e. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.42 (d, J=1.7 Hz, 1H), 7.97 (d, J=5.6 Hz, 1H), 7.83 (dd, J=8.8, 2.4 Hz, 1H), 6.78 (d, J=9.0 Hz, 1H), 6.06 (d, J=5.6 Hz, 1H), 4.17 (q, J=7.1 Hz, 2H), 3.94-4.01 (m, 4H), 3.87-3.94 (m, 4H), 3.83 (s, 2H), 3.59-3.67 (m, 4H), 3.50-3.59 (m, 4H), 1.50 (s, 9H), 1.25 (t, J=7.1 Hz, 3H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C28H37N7O5: 552.3 (M+H). Found: 552.2.

Provenance & Evidence