Synthesis
GENERAL METHOD: 1-methyl-4-(4-nitrophenyl)piperazine (5.53 mmol) was dissolved in methanol (15 mL) and stirred under N2 atmosphere. Pd/C (2.78 mmol) was added to this solution. Subsequently, the reaction flask was placed in H2 atmosphere (balloon) for hydrogenation reaction overnight. Upon completion of the reaction, the reaction mixture was filtered through a diatomaceous earth plate and the filtrate was concentrated under vacuum. The crude product was purified by silica gel column chromatography (eluent: 5% MeOH/DCM containing 1% NH3) to afford the target compound 4-(4-methyl-1-piperazinyl)aniline (3a) as a brown solid in 87% yield.
References
[1] Journal of Medicinal Chemistry, 2005, vol. 48, # 26, p. 8261 - 8269
[2] European Journal of Medicinal Chemistry, 2016, vol. 124, p. 896 - 905
[3] Patent: US6569878, 2003, B1
[4] Patent: EP1215208, 2002, A2. Location in patent: Example C(70)
[5] Patent: WO2012/110773, 2012, A1. Location in patent: Page/Page column 58; 59
