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

Participants

Reaction Steps

Compound 26a (131 mg, 0.268 mmol) and 2-bromoquinoline (558 mg, 2.68 mmol) were placed in an 8 mL vial equipped with a stir bar and then the vial was evacuated and backflushed with argon. Dry DMF (4 mL) and DIEA (0.468 mL, 2.68 mmol) were added via syringe and then the mixture was deoxygenated by bubbling argon through the stirred solution for 5 min. CuI (2.56 mg, 0.0134 mmol) and (Ph3P)2PdCl2 (18.9 mg, 0.0268 mmol) were added and then the reaction was stirred at rt for 1 h. The reaction was poured into water (50 mL) and then the mixture was extracted with EtOAc (3×30 mL). The combined organic extracts were washed with water (20 mL) and brine (2×20 mL) and then dried over MgSO4 and filtered. The solution was concentrated 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 26b. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.97 (d, J=2.2 Hz, 1H), 8.27 (dd, J=8.9, 2.3 Hz, 1H), 8.12 (t, J=8.6 Hz, 2H), 8.04 (d, J=5.6 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 7.67-7.77 (m, 1H), 7.62 (d, J=8.6 Hz, 1H), 7.49-7.59 (m, 1H), 6.81 (d, J=8.8 Hz, 1H), 6.09 (d, J=5.6 Hz, 1H), 3.98-4.07 (m, 4H), 3.88-3.98 (m, 4H), 3.61-3.70 (m, 4H), 3.51-3.61 (m, 4H), 1.50 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C35H36N8O3: 617.3 (M+H). Found: 617.3.

Provenance & Evidence