Tetrahydrofuran → 3-[3,4-dimethyl-5-(2-methyl-2H-[1,2,4]triazol-3-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 1-methyl-1,2,4-triazole (0.056 mL, 0.74 mmol) and THF (2 mL) is added a 1.6 M solution of n-BuLi in hexanes (0.46 mL, 0.74 mmol). The solution is warmed to ambient temperature and stirred for 30 minutes. The solution is cooled to 0° C., a 0.5 M solution of ZnCl2 in THF (4.70 mL, 2.33 mmol) is added and the solution warmed to ambient temperature and stirred for 30 minute. 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 PdCl2(dppf) (0.009 g, 0.012 mmol) is added and the solution heated at 65° C. overnight, diluted with EtOAc (25 mL), washed with sat. NH4Cl (20 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (15%-60% EtOAc/hexane gradient), followed by a second purification by ISCO column chromatography (100% Et2O) furnish the title compound (0.07 g, 0.17 mmol, 70%). 1H NMR (CDCl3) δ 0.87 (t, J=7.5 Hz, 6H), 1.73-1.92 (m, 4H), 2.06 (s, 3H), 2.29 (s, 3H), 2.47 (s, 3H), 2.51 (s, 3H), 3.27-3.37 (m, 1H), 3.97 (s, 3H), 6.69 (s, 1H), 8.00 (s, 1H). LC/MS (m/z): calcd. for C22H28N6S (M+H)+: 409.6; found: 409.2.

Provenance & Evidence