Tetrahydrofuran → 3-[3,4-Dimethyl-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

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Reaction Steps

To a −78° C. solution of 3-iodo-pyridine (0.15 g, 0.74 mmol) and 0.5 M ZnCl2 in THF (1.5 mL, 0.75 mmol) is added t-BuLi (0.88 mL, 1.49 mmol). The slurry is warmed to ambient temperature and stirred for 30 minutes. 3-(5-bromo-3,4-dimethyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.10 g, 0.25 mmol) and Pd(PPh3)4 (0.014 g, 0.012 mmol) are added and the solution stirred at ambient temperature for 2 days, diluted with EtOAc (35 mL), washed with sat. NH4Cl (30 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20%-30% EtOAc/hexane gradient) furnish the title compound (6.1 mg, 0.015 mmol, 6%). 1H NMR (CDCl3), δ 0.88 (t, J=7.5 Hz, 6H), 1.74-1.92 (m, 4H), 2.07 (s, 3H), 2.29 (s, 3H), 2.49 (s, 3H), 2.53 (s, 3H), 3.30-3.39 (m, 1H), 6.68 (s, 1H), 7.36 (dd, J=8.0, 4.5 Hz, 1H), 7.79-7.83 (m 1H), 8.57 (d, J=4.5 Hz, 1H), 8.79 (d, J=0.9 Hz, 1H). LC/MS (m/z): calcd. for C24H28N4S (M+H)+: 405.6; found: 405.2.

Provenance & Evidence