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

Participants

Reaction Steps

Compound 21a (195 mg, 0.393 mmol) was placed in an 8 mL vial equipped with a stir bar and then DCM (2 mL) was added. The Dess-Martin periodinane (184 mg, 0.433 mmol) was added and then the reaction was stirred at rt for 20 min. The reaction was diluted with DCM (20 mL) and washed with saturated NaHCO3 solution (2×20 mL). The organic phase was dried over MgSO4 and filtered. The solvent was removed under reduced pressure. The residue was placed in a 20 mL vial equipped with a stir bar and then MeOH (5 mL) was added. K2CO3 (163 mg, 1.18 mmol) was added and then dimethyl (1-diazo-2-oxopropyl)phosphonate (113 mg, 0.590 mmol) dissolved in MeOH (2 mL) was added. The reaction was stirred at reflux for 3 h. Additional K2CO3 (163 mg, 1.18 mmol)) and diazophosphonate (113 mg, 0.590 mmol) were added and the reaction was refluxed for 6 h. The reaction was cooled to rt and then the solvent was removed under reduced pressure. The residue was dissolved in DCM (20 mL) and washed with water (20 mL). The aqueous layer was extracted with DCM (3×10 mL) and then the combined organic extracts were washed with brine (20 mL), dried over MgSO4, and filtered. The solvent was removed under reduced pressure. The crude product was chromatographed on a 40 g SiO2 pre-packed column eluting with 0-60% ACN/DCM to afford compound 26a. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.85 (d, J=2.2 Hz, 1H), 8.16 (dd, J=8.8, 2.4 Hz, 1H), 8.03 (d, J=5.6 Hz, 1H), 6.77 (d, J=9.0 Hz, 1H), 6.08 (d, J=5.6 Hz, 1H), 3.95-4.03 (m, 4H), 3.88-3.95 (m, 4H), 3.60-3.68 (m, 4H), 3.50-3.60 (m, 4H), 3.28 (s, 1H), 1.50 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C26H31N7O3: 490.3 (M+H). Found: 490.3.

Provenance & Evidence