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

Participants

Reaction Steps

Crude compound 21b (140 mg, 0.284 mmol) was placed in a 50 mL round bottom flask equipped with a stir bar and then 2-aminoquinoline (49.1 mg, 0.340 mmol) was added. DCE (10 mL) and AcOH (32.5 μL, 0.567 mmol) were added and then NaBH(OAc)3 (180 mg, 0.851 mmol) was added as a solid. The reaction was stirred at rt for 20 h and then additional NaBH(OAc)3 (60.0 mg, 0.283 mmol) was added. After 24 h, more NaBH(OAc)3 (60.0 mg, 0.283 mmol) was added and the reaction was stirred for an additional 20 h. The reaction was poured into saturated NaHCO3 solution (30 mL) and extracted with DCM (3×10 mL), and then the combined organic extracts were dried over MgSO4 and filtered. The solvent was removed under reduced pressure. The crude product was chromatographed on a 12 g SiO2 pre-packed column eluting with 0-100% ACN/DCM to afford compound 21c. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.52 (d, J=2.0 Hz, 1H), 8.00 (d, J=5.4 Hz, 1H), 7.88 (dd, J=8.8, 2.2 Hz, 1H), 7.80 (d, J=9.0 Hz, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.58 (d, J=7.8 Hz, 1H), 7.52 (t, J=7.7 Hz, 1H), 7.21 (t, J=7.5 Hz, 1H), 6.76 (d, J=8.8 Hz, 1H), 6.71 (d, J=9.0 Hz, 1H), 6.08 (d, J=5.9 Hz, 1H), 5.49 (br. s., 1H), 4.87 (d, J=4.9 Hz, 2H), 3.88-4.01 (m, 8H), 3.52-3.65 (m, 8H), 1.50 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C34H39N9O3: 622.3 (M+H). Found: 622.3.

Provenance & Evidence