Synthesis
Step 1: Piperazine (10.20 g, 2.45 mmol) was dissolved in 15 mL of isopropanol in a dry round-bottomed flask under nitrogen protection. Subsequently, 2-chloroquinoline (0.20 g, 1.2 mmol) was added and the reaction mixture was heated and stirred at reflux for 24 hours. After completion of the reaction, water was added to the mixture and extracted with ethyl acetate. The organic layers were combined, washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to remove the solvent. The crude product obtained was purified by silica gel column chromatography with eluent ratio of dichloromethane:methanol=4:1 to afford the target compound 2-(piperazin-1-yl)quinoline in 36% yield.
References
[1] Patent: EP1724267, 2006, A1. Location in patent: Page/Page column 35; 68
[2] Journal of Medicinal Chemistry, 2010, vol. 53, # 21, p. 7549 - 7563
[3] Journal of Pharmaceutical Sciences, 1992, vol. 81, # 1, p. 99 - 103
[4] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 10, p. 1314 - 1320
[5] Patent: WO2004/46124, 2004, A1. Location in patent: Page 41