Chlorotrimethylsilane → (E)-tert-Butyl 4-(5-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[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 (4 mL) was added. 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 an 8 mL vial equipped with a stir bar and then dry DMF (4 mL) was added. 2-Methylquinoline (51.5 μL, 0.393 mmol) and TMSCl (150 μL, 1.18 mmol) were added sequentially and then the mixture was heated to 80° C. and stirred for 3 h. The reaction was cooled to rt and then poured into water (50 mL) and neutralized with saturated NaHCO3 solution (50 mL). The aqueous mixture was extracted with EtOAc (3×50 mL), and then the organic extracts were combined, washed with brine (2×50 mL), dried over Na2SO4, and filtered. The solvent was removed under reduced pressure. The crude product was chromatographed on a 12 g SiO2 pre-packed column eluting with 0-80% EtOAc/DCM to afford compound 30a. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.50 (d, J=2.0 Hz, 1H), 8.07 (dd, J=8.4, 4.3 Hz, 2H), 7.88-7.98 (m, 3H), 7.65-7.78 (m, 4H), 7.44-7.51 (m, 1H), 6.83 (d, J=8.8 Hz, 1H), 6.05 (d, J=5.6 Hz, 1H), 4.02-4.10 (m, 4H), 3.92-4.01 (m, 4H), 3.63-3.71 (m, 4H), 3.57-3.63 (m, 4H), 1.51 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C35H38N8O3: 619.3 (M+H). Found: 619.3.

Provenance & Evidence