Diethyl Ether → 4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [4-(4-{3-[2-(4fluorophenyl)acetyl]thioureido}phenoxy)pyridin-2-yl]amide

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Reaction Steps

4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (63 mg) was dissolved in ethanol (1.5 ml) under a nitrogen atmosphere, and then (S)-(+)-10-camphorsulfonic acid (111 mg) was added thereto, followed by stirring for 5 min. A 0.25 M solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.954 ml) was added thereto, followed by stirring for 13.5 hrs. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (30 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml), water (30 ml), brine (30 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; heptane:ethyl acetate=1:8, ethyl acetate, then ethyl acetate:ethanol=95:5). Fractions containing the target compound were concentrated under reduced pressure to give a residue, to which diethyl ether (2 ml) and hexane (2 ml) were then added to suspend. The solid was filtered off, and dried under aeration to provide the titled compound (34.1 mg, 36.2%) as white powder.

Provenance & Evidence