Hydrochloric Acid → 3-(3-Chloro-4-pyridin-4-yl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine, hydrochloride salt

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Reaction Conditions

Reaction Steps

A solution of 3-(4-bromo-3-chloro-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.25 g, 0.61 mmol), 4-pyridyl-boronic acid (0.82, 0.67 mmol), a 2 M solution of Na2CO3 (0.5 mL, 0.91 mmol), and n-PrOH (2.5 mL) are degassed with nitrogen for 10 minutes. Pd(OAc)2 (0.0027 g, 0.012 mmol) and PPh3 (0.0095 g, 0.036 mmol) are added, and the solution heated at a 90° C. overnight. The solution is diluted with ethyl acetate (40 mL) and washed with a 10% solution of Na2CO3 (30 mL). The organic layer is dried over MgSO4, filtered, and concentrated. The residue is purified by ISCO flash chromatography (20%-30% EtOAc gradient). The resulting product is dissolved in dichloromethane (5 mL), treated with a 1 M solution of HCl in EtOH (0.35 mL, 0.35 mmol), and concentrated. The residue is recrystallized from acetonitrile and ethyl acetate furnish the title compound (0.15 g, 0.34 mmol, 56%). 1H-NMR (CDCl3), δ 0.95 (t, J=7.5 Hz, 6H), 1.73-1.88 (m, 2H), 1.89-2.04 (m, 2H), 2.68 (s, 3H), 2.82 (s, 3H), 3.87-3.97 (m, 1H), 7.28 (s, 1H), 8.26-8.34 (m, 3H), 8.95 (d, J=5.3 Hz, 2H) ppm. LC/MS (m/z): calcd. for C22H24Cl2N4S (M+H)+: 411.1; found: 411.2.

Provenance & Evidence