General procedure for the synthesis of (S)-6-(3-methylpiperazin-1-yl)nicotinonitrile from 2-chloro-5-cyanopyridine and (S)-2-methylpiperazine: to a solution of DMF (15 mL) containing 6-chloronicotinonitrile (1.38 g, 10 mmol, 1 eq.) and (S)-2-methylpiperazine (1.00 g, 10 mmol) was added triethylamine (4.13 g. 3 mL, 40.8 mmol, 4 equiv). The reaction mixture was stirred at room temperature for 14 h, during which the formation of a white triethylamine hydrochloride precipitate was observed. Upon completion of the reaction, water (15 mL) and ethyl acetate (100 mL) were added for extraction, the organic layer was separated, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a white residue. The solid was further dried under high vacuum to afford the target product (S)-6-(3-methylpiperazin-1-yl)nicotinonitrile as a white solid (1.4 g, 69% yield). The 1H NMR (400 MHz, chloroform-d) data of the product were as follows: δ 8.38 (s, 1H), 7.58 (d, J = 9.60 Hz, 1H), 6.59 (d, J = 9.09 Hz, 1H), 4.19-4.31 (m, 2H), 3.08-3.15 (m, 1H), 2.92-3.04 (m, 1H), 2.81 -2.91 (m, 2H), 2.57-2.65 (m, 1H), 1.15 (d, J = 6.32Hz, 3H).
