Sodium Bicarbonate → Ethyl 2-[6-[3-[4-(diphenylmethoxy)piperidino] propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate difumarate

関与物質

反応手順

4.2 g of 4-(diphenylmethoxy)-1-piperidinepropanamine and 1.76 g of ethyl 2-[6-chloroimidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate were stirred at 190-200° C. for 3.5 hours. After cooling, aqueous sodium bicarbonate was added, followed by extraction with ethyl acetate; the extract was washed with saturated saline and dried with magnesium sulfate. After the dry product was concentrated under reduced pressure, the residue was subjected to silica gel column chromatography and eluted with ethyl acetate:methanol:triethylamine (100:5:1). The desired fraction was collected, dissolved in 16 ml of ethyl acetate; a solution of 867 mg of fumaric acid in 16 ml of methanol was added, followed by concentration. Acetone was added to the residue; the crystal precipitated was collected by filtration, washed with acetone and dried to yield 2.30 g of the title compound.

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