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

Participants

Reaction Conditions

Reaction Steps

Compound 21a (152 mg, 0.307 mmol) was placed in an 8 mL vial equipped with a stir bar and then DCM (2 mL) and DIEA (107 mL, 0.615 mmol) were added. The solution was cooled to 0° C. and MsCl (35.8 mL, 0.461 mmol) was added dropwise via microsyringe. The reaction was stirred at 0° C. for 15 min and then the solvent was removed under reduced pressure. The crude material was placed in a 50 mL round bottom flask equipped with a stir bar and then 2-quinolinethiol (56.2 mg, 0.338 mmol) and K2CO3 (63.7 mg, 0.461 mmol) were added. Dry ACN (10 mL) was added and then the reaction was stirred at rt for 20 h. The reaction was diluted with water (20 mL) and extracted with DCM (3×30 mL). The combined organic extracts were washed with brine (20 mL) and then 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 0-60% ACN/DCM to afford compound 22a. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.54 (d, J=2.2 Hz, 1H), 7.96 (d, J=5.6 Hz, 1H), 7.84 (d, J=8.6 Hz, 2H), 7.87 (d, J=8.8 Hz, 1H), 7.70 (d, J=7.8 Hz, 1H), 7.56-7.66 (m, 1H), 7.38-7.47 (m, 1H), 7.26 (d, J=6.1 Hz, 1H), 6.69 (d, J=8.8 Hz, 1H), 6.03 (d, J=5.6 Hz, 1H), 4.85 (s, 2H), 3.89-3.98 (m, 4H), 3.81-3.89 (m, 4H), 3.56 (d, J=5.4 Hz, 8H), 1.49 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C34H38N8O3S: 639.3 (M+H). Found: 639.4.

Provenance & Evidence