Tetrahydrofuran → HCID 57932976, compound

Participants

Reaction Conditions

Reaction Steps

To a −78° C. solution of 3-(5-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.50 g, 1.27 mmol), and THF (5 mL) is added 1.34 M n-Bu-Li (1.0 mL, 1.34 mmol). The solution is stirred for at −78° C. for 30 minutes and 0.5 M ZnCl2 in THF (2.7 mL, 1.34 mmol) is added and the solution warmed to ambient temperature. After 30 minutes 3-bromopyridine (0.15 mL, 1.53 mmol) and PdCl2(dppf) (0.047 g, 0.064 mmol) is added and the solution heated at 65° C. overnight. The solution is diluted with CH2Cl2 (40 mL), washed with 10% citric acid (20 mL), water (20 mL), brine (20 mL) dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20%-40% EtOAc/hexane gradient) concentrated and re-dissolved in Et2O. The solution is treated with Darco®-60 for 15 minutes, dried over Na2SO4, and filtered thru Celite® furnish the title compound (0.26 g, 0.67 mmol, 52%). 1H NMR (CDCl3), δ 0.88 (t, J=7.5 Hz, 6H), 1.74-1.92 (m, 4H), 2.17 (s, 3H), 2.50 (s, 3H), 2.52 (s, 3H), 3.28-3.38 (m, 1H), 6.68 (s, 1H), 7.26-7.32 (m, 2H), 7.86 (dt, J=7.9, 1.8 Hz, 1H), 850 (d, J=3.2 Hz, 1H), 8.89 (s, 1H). LC/MS (m/z): calcd. for C23H26N4S (M+H)+: 391.6; found: 391.2.

Provenance & Evidence