Tetrahydrofuran → 2-[8-(1-Ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-thiophene-3-carbonitrile

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Reaction Steps

To a solution 0.05 g/mL of Reike® Zn (31 mL, 23.93 mmol) is added 2-bromo-thiophene-3-carbonitrile (Fournari, P. et al. Bull. Soc. Chim. Fr., 1967, 4115) (2.25 g, 11.96 mmol) and THF (5 mL). The solution is heated at a reflux for 2 hours, cooled to ambient temperature and the excess Zn allowed to settle. The solution is transferred via a cannula into a flask of 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (2.5 g, 7.98 mmol) and PdCl2(dppf) (0.29 g, 0.040 mmol). The mixture is heated at 65° C. overnight, diluted with EtOAc (75 mL), washed with sat. NH4Cl (2×75 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (10%-20% EtOAc/hexane gradient) furnish the title compound (1.10 g, 3.39 mmol, 42%). 1H NMR (CDCl3) δ 0.86 (t, J=7.5 Hz, 6H), 1.74-1.91 (m, 4H), 2.55 (s, 3H), 2.61 (s, 3H), 3.25-3.34 (m, 1H), 6.75 (s, 1H), 7.35 (d, J=5.2 Hz, 1H), 7.53 (d, J=5.2 Hz, 1H). LC/MS (m/z): calcd. for C18H20N4S (M+H)+: 325.5; found: 325.2.

Provenance & Evidence