Carbon Dioxide → 2-[[4-[(6-Chloronaphthalen-2-yl)sulfonyl]piperazin-1-yl]carbonyl]-6-methyl-4,5,6,7-tetrahydrofuro[2,3-c]pyridine Hydrochloride

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-methyl-4,5,6,7-tetrahydrofuro[2,3-c]pyridine (58.1 mg) in tetrahydrofuran (3.2 ml), n-butyl lithium (a 1.59N hexane solution, 320 μl) was added at −78° C., followed by stirring for 1 hour and then at 0° C. for 30 minutes. The reaction mixture was cooled to −78° C. and a carbon dioxide gas was introduced thereinto for 1 hour. After the reaction mixture was heated to room temperature over 30 minutes, it was concentrated. To a solution of the resulting residue in N,N-dimethylformamide (6.0 ml), 1-[(6-chloronaphthalen-2-yl)sulfonyl]piperazine hydrochloride (177 mg, 510 μmol) was dissolved, followed by the addition of 1-(dimethylaminopropyl)-3-ethylcarbodiimide (98.0 mg, 511 μmol) and 1-hydroxybenzotriazole (69.0 mg, 511 μmol) at room temperature and then, diisopropylethylamine (185 μl, 1.06 mmol) at 0° C. After stirring overnight at room temperature, the reaction mixture was added with methylene chloride (20 ml) and a saturated aqueous solution (50 ml) of sodium bicarbonate, whereby the organic layer was separated. The resulting organic layer was extracted with methylene chloride (2×10 ml). The organic layers were combined, washed with water (50 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified twice by preparative thin-layer chromatography on a silica gel (methylene chloride:acetone:methanol=10:5:1). The white solid thus obtained was dissolved in a 1N ethanol hydrochloride solution and the resulting solution was concentrated. After the addition of water, the mixture was concentrated again, whereby the title compound (74.7 mg) was obtained as a white solid.

Provenance & Evidence