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

Participants

Reaction Steps

Compound 20c (258 mg, 0.506 mmol) was placed in a 20 mL vial equipped with a stir bar and then DCM (4 mL) and DMF (10 μL) were added. Oxalyl chloride (66.2 μL, 0.759 mmol) was added dropwise via syringe and the reaction was stirred for 20 min. The solvent was removed under reduced pressure. The residue was dissolved in DCM (25 mL) and then DIEA (440 μL, 2.53 mmol) and 2-aminoquinoline (87.5 mg, 0.607 mmol) were added sequentially. The reaction was stirred at rt for 16 h and then poured into water (20 mL) and separated. The aqueous layer was extracted with DCM (3×10 mL) and the combined organic layers were 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 0-100% EtOAc/DCM to afford compound 20d. 1H-NMR (400 MHz, CDCl3) δ (ppm): 9.99 (s, 1H), 8.59-8.64 (m, 2H), 8.16 (d, J=9.0 Hz, 1H), 8.06 (d, J=5.6 Hz, 1H), 7.96 (dd, J=8.8, 2.4 Hz, 1H), 7.90 (d, J=8.3 Hz, 1H), 7.78 (d, J=8.1 Hz, 1H), 7.65-7.71 (m, 1H), 7.42-7.48 (m, 1H), 6.79 (d, J=8.8 Hz, 1H), 6.15 (d, J=5.9 Hz, 1H), 4.04-4.10 (m, 4H), 3.98-4.04 (m, 4H), 3.63-3.70 (m, 4H), 3.54-3.60 (m, 4H), 1.50 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C34H37N9O4: 636.3 (M+H). Found: 636.4.

Provenance & Evidence