Methanol → HCID 178498530, compound

Participants

Reaction Steps

To a solution of tert-butyl (1-{4-[8-(benzyloxy)-6-chloro-3-phenylimidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutyl)carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-17 (0.91 g, 1.48 mmol) in MeOH (20 mL) and THF (2 mL) in an autoclave was added 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride (0.24 g, 0.30 mmol, 0.20 equiv) and triethylamine (0.23 mL, 1.63 mmol, 1.1 equiv.). The autoclave was flushed with CO (approximately 5 bar) three times, then was pressurized with CO (5.2 bar), stirred at room temperature 30 min., and briefly placed under reduced atmosphere (0.06 bar). The autoclave was then pressurized with CO (5.9 bar at 20° C.), heated to 100° C., and stirred at this temperature for 18 h. The resulting solution was concentrated under reduced pressure. The resulting material was purified using MPLC (Biotage Isolera; Snap 25 g cartridge, 100% hexane 2.0 min, gradient to 80% hexane/20% EtOAc 1.0 min, 80% hexane/20% EtOAc 3.0 min, gradient to 50% hexane/50% EtOAc 6.0 min, 50% hexane/50% EtOAc 6.5 min, gradient to 10% hexane/90% EtOAc 6.0 min, gradient to 100% EtOAc 2.7 min, 100% EtOAc 26.7 min) to give methyl 2-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-8-hydroxy-3-phenylimidazo[1,2-b]pyridazine-6-carboxylate (0.34 g, 44%):

Provenance & Evidence