(R)-6-(3-methylpiperazin-1-yl)nicotinonitrile

33252-28-7

75336-86-6

1057682-05-9

The general procedure for the synthesis of (R)-6-(3-methylpiperazin-1-yl)nicotinonitrile from 2-chloro-5-cyanopyridine and (R)-(-)-2-methylpiperazine was as follows: to a solution of acetonitrile (80 mL) containing 6-chloro-pyridine-3-carbonitrile (10 g, 0.06 mol) and (2R)-2-methylpiperazine (6.35 g, 0.06 mol) was added K2CO3 (12.0 g, 0.09 mol). The reaction mixture was heated to 60 °C and stirred for 2 h at room temperature (completion of the reaction was monitored by TLC). After the reaction was cooled to room temperature, the reaction was quenched with water (150 mL) and subsequently extracted with EtOAc (3 x 80 mL). The organic phases were combined, dried with anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (100-200 mesh silica gel, 5% MeOH-DCM as eluent) to afford the target product (R)-6-(3-methylpiperazin-1-yl)nicotinonitrile (10.0 g, 69% yield).