3-[(4-Methylpiperazin-1-yl)methyl]benzonitrile

Uses

3-((4-Methylpiperazin-1-yl)methyl)benzonitrile is involved in the preparation of N-Hydroxyphenylacrylamides and N-Hydroxypyridin-2-ylacrylamides as novel histone deacetylase inhibitors.

Synthesis

General procedure for the synthesis of 3-((4-methylpiperazin-1-yl)methyl)benzonitrile from N-methylpiperazine and 3-cyanobenzaldehyde: Step 1: 3-Formylbenzonitrile (1.5 g, 11.45 mmol), N-methylpiperazine (1.49 g, 14.9 mmol) and sodium triacetoxyborohydride (3.63 g, 17.18 mmol) were dissolved in dichloromethane (75 ml), acetic acid (0.851 ml, 14.9 mmol) was added and the reaction was stirred at room temperature overnight. After completion of the reaction, the reaction mixture was diluted with dichloromethane and washed with 1 M sodium carbonate solution. The organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (eluent: dichloromethane/methanol/ammonia = 97:3:0.5) to give 3-(4-methylpiperazin-1-ylmethyl)benzonitrile 1.7 g in 70% yield.

References

[1] Patent: WO2007/113249, 2007, A2. Location in patent: Page/Page column 60-61
[2] Journal of Medicinal Chemistry, 2010, vol. 53, # 2, p. 822 - 839
[3] Patent: EP2033956, 2009, A1. Location in patent: Page/Page column 13
[4] Patent: WO2006/130075, 2006, A1. Location in patent: Page/Page column 25-26