Dichloromethane → tert-Butyl 4-(5-(8-morpholino-2-((quinolin-2-ylsulfonyl)methyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazine-1-carboxylate

Participants

Reaction Steps

Compound 21a (152 mg, 0.307 mmol) was placed in an 8 mL vial equipped with a stir bar and then DCM (4 mL) was added and the solid dissolved. Thionyl chloride (54.7 μL, 0.750 mmol) was added dropwise via microsyringe and then the reaction was stirred at rt for 5 min. The solvent was removed under reduced pressure. The residue was placed in a 40 mL vial equipped with a stir bar and then acetone was added. Compound 24a (199 mg, 1.00 mmol) was dissolved in water (5 mL) and added to the stirred acetone solution. The reaction turned yellow immediately. The reaction was stirred at rt for 18 h and then diluted with EtOAc (30 mL). The organic layer was separated and then the aqueous layer was extracted with EtOAc (3×20 mL). The aqueous layer was then extracted with DCM (3×30 mL). The organic extracts were combined, dried over MgSO4, and filtered. The solvent was removed under reduced pressure. The crude residue was chromatographed on a 12 g SiO2 pre-packed column eluting with 0-80% ACN/DCM to afford compound 24b. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.47 (d, J=2.2 Hz, 1H), 8.33 (d, J=8.6 Hz, 1H), 8.29 (d, J=8.6 Hz, 1H), 7.93-7.98 (m, 2H), 7.92 (d, J=5.6 Hz, 1H), 7.85-7.90 (m, 1H), 7.83 (dd, J=8.8, 2.4 Hz, 1H), 7.72-7.78 (m, 1H), 6.68 (d, J=8.8 Hz, 1H), 5.93 (d, J=5.6 Hz, 1H), 5.07 (s, 2H), 3.59-3.64 (m, 4H), 3.55-3.59 (m, 4H), 3.36-3.41 (m, 4H), 3.29-3.36 (m, 4H), 1.51 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C34H38N8O5S: 671.3 (M+H). Found: 671.3.

Provenance & Evidence