Mechlorethamine → 1-Methyl-4-(pyridin-2-yl)piperidine-4-carbonitrile

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A solution of 2-pyridyl acetonitrile (1.0 g, 8.54 mmol) in DMSO (8 mL) was treated with sodium hydride (1.195 g, 29.88 mmol) portionwise. The resulting brown suspension was stirred at 23° C. for 30 minutes. 2-Chloro-N-(2-chloroethyl)-N-methylethanamine (1.81 g, 9.39 mmol) was then slowly added over 5 minutes, then the suspension was heated at 65° C. overnight. The reaction was then diluted with 1N hydrochloric acid and washed with ethyl acetate (2×). The aqueous phase was basified with 1N sodium hydroxide and extracted with ethyl acetate (3×). The combined extracts were washed with water (5×) and brine, dried over anhydrous magnesium sulfate, filtered and concentrated to give an oil. This was purified on Biotage silica gel column (1% to 10% (methanol+1% ammonia) in dichloromethane) to give the desired product as an oil (0.583 g, 34%). 1H NMR (400 MHz, CDCl3) δ ppm: 2.14-2.25 (2H, m), 2.30-2.38 (2H, m), 2.40 (3H, s), 2.51 (td, J=12.25 and 2.27 Hz), 2.99 (2H, d, J=12.13 Hz), 7.25-7.36 (1H, m), 7.56 (1H, d, J=8.08 Hz), 7.75 (1H, td, J=7.71 and 1.77 Hz), 8.64 (1H, d, J=4.80 Hz). LC/MS (M+H)+: 202. HPLC ret. time (Condition E): 1.025 min.

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