4-Toluenesulfonyl chloride → 8-{4-[2-(1-Benzofuran-3-yl)ethyl]-1-piperazinyl}-6-fluoroquinoline

Participants

Reaction Steps

To a stirred solution of 2-(1-benzofuran-3-yl)ethanol (815 mg, 5 mmol) in anhydrous pyridine (20 ml), p-toluenesulfonyl chloride (1.14 g, 6.0 mmol) was added. The reaction mixture was kept at 0° C. for 48 hrs and quenched with ice cold water. The reaction mixture was extracted with chloroform, washed well with water, and dried over anhydrous MgSO4. It was then filtered and concentrated. The crude product obtained was taken to next step without any purification. A mixture of tosylate (316 mg. 1 mmol) (obtained by the above mentioned process) and 6-fluoro-8-piperazino quinoline (231 mg, 1 mmol) was heated at 120° C. in DMSO in the presence of N,N-diisopropylethylamine (5 ml, excess) for 24 hrs. At the end, reaction mixture was quenched with water and extracted with chloroform. The organic layer was washed with water and dried over anhydrous MgSO4 and concentrated to dryness. The dark colored solid was purified by silica-gel column chromatography by initially eluting it with 70% ethyl acetate:hexane and then with 55% methanol:ethyl acetate. The product, 8-{4-[2-(1-benzofuran-3-yl)ethyl]-1-piperazinyl}-6-fluoroquinoline, was isolated as yellow oil. Yield: 220 mg (58%); (M+H): 376. 1HNMR (400 MHz, CDCl3):δ 8.82˜8.80 (dd, J1=1.7 Hz, J2=1.7 Hz, 1H), 8.08˜8.03 (dd, J1=1.8 Hz, J2=1.8 Hz, 1H), 7.69˜6.32 (m, 8H), 3.50˜2.63 (m, 12H).

Provenance & Evidence