Dimethylformamide → HCID 86716512, compound

Participants

Reaction Steps

A mixture of 2-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-3-phenylimidazo[1,2-b]pyridazine-6-carboxylic acid that was prepared in a manner analgous to that described for Intermediate Example Int-27 (0.40 g, 0.82 mmol), O,N-dimethylhydroxylamine hydrochloride (0.12 g, 1.24 mmol, 1.5 equiv), PYBOP (0.54 g, 1.03 mmol, 1.25 equiv) and N,N-diisopropylethylamine (0.9 mL, 4.95 mmol, 6.0 equiv) in DMF (15 mL) was stirred at room temperature for 21 h. The resulting mixture was added to ice water (50 mL). The aqueous mixture was extracted with EtOAc (4×25 mL). The combined organic phases were sequentially washed with water (25 mL) and a saturated aqueous NaCl solution (25 mL), dried (Na2SO4 anh.) and concentrated under reduced pressure. The resulting brown oil (1.48 g) 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 4.5 min) to give tert-butyl {1-[4-(6-{4-[methoxy(methyl)carbamoyl]phenyl}-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate (0.25 g, 57%):

Provenance & Evidence