Tetrahydrofuran → 8-(1-Ethyl-propyl)-3-(3-methoxy-5-pyridin-3-yl-thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

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Reaction Steps

To a −78° C. solution of 3-iodo-pyridine (0.32 g, 1.56 mmol) and 0.5 M ZnCl2 in THF (3.20 mL, 1.59 mmol) is added t-BuLi (2.27 mL, 3.85 mmol). The solution is warmed to ambient temperature and stirred for 30 minutes. 3-(5-bromo-3-methoxy-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.26 g, 0.64 mmol) and Pd(PPh3)4 (0.037 g, 0.032 mmol) are added and the solution heated at 50° C. for 1 hour, cooled to ambient temperature and stirred overnight. The solution is diluted with EtOAc (30 mL), washed with sat. NH4Cl (2×30 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20%-50% EtOAc/hexane gradient), furnish the title compound (0.16 g, 0.39 mmol, 61%). 1H NMR (CDCl3) δ 0.87 (t, J=7.5 Hz, 6H), 1.74-1.91 (m, 4H), 2.52 (s, 3H), 2.55 (s, 3H), 3.28-3.38 (m, 1H), 3.93, (3H), 6.67 (s, 1H), 7.26 (d, J=3.5 Hz, 1H), 7.31-7.36 (m, 1H), 7.88-7.92 (m, 1H), 8.55 (d, J=4.5 Hz, 1H), 8.92 (d, J=1.8 Hz, 1H). LC/MS (m/z): calcd. for C23H26N4OS (M+H)+: 407.6; found: 407.4.

Provenance & Evidence