Sodium Bicarbonate → (2S)-2-{[4-(6-methoxyquinolin-2-yl)piperazin-1-yl]methyl]-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinoline

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Reaction Conditions

Reaction Steps

A mixture of 6-methoxy-2-piperazin-1-yl-quinoline of Step D (1.05 g, 4.31 mmol) in dimethylsulfoxide (15 mL) and [(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl-4-bromobenzene sulfonate (1.62 g) is heated at 80° C. under nitrogen for 3 hours and at 90° C. for 1 additional hour. The solution is poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The extracts are dried over anhydrous magnesium sulfate and evaporated to dryness. The residue is flash chromatographed on silica gel Merck-60 using a gradient of methanol (0.5–3%) in dichloromethane-hexane (1:1) containing 0.1% ammonium hydroxide to provide the title compound (0.790 g). The pure material is charcoalized (in ethyl acetate), filtered, evaporated and induced to crystallize from hexane by sonication. The off-white solid melts at 158–160° C.

Provenance & Evidence