Hydrochloric Acid → 7-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-(2-methylphenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine

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Reaction Conditions

Reaction Steps

7-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (0.330 g, 1 mmol, Example 1), 1-bromo-2-methylbenzene (0.132 mL, 1.100 mmol), palladium(II)acetate (0.011 g, 0.050 mmol), triphenylphosphine (0.026 g, 0.100 mmol) and cesium carbonate (0.342 g, 1.050 mmol) were suspended in 1,4-dioxane (5 ml) under argon. The mixture was degassed 3 times and heated at 90° C. for 16 h. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (50 ml) and water (50 ml). The aqueous phase was extracted with ethyl acetate (2×50 ml), the combined organic extracts were washed with water (3×50 ml), brine (50 ml) dried over anhydrous sodium sulfate and concentrated to a crude oil. The crude oil was purified by mass-directed automated preparative HPLC to afford the free base that was dissolved in dichloromethane (5 ml) and treated with 4N HCl in dioxane. The solvents were removed in vacuo and the solid tritruated with diethyl ether to afford 7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-(2-methylphenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (0.027 g, 0.059 mmol, 5.92% yield).

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