54864-83-4

5326-23-8

124-40-3

54864-83-4

Scheme 32: Synthesis of 6-chloro-N,N-dimethylnicotinamide [198] 6-Chloronicotinic acid [197] (3.0 g, 19.0 mmol) was dissolved in tetrahydrofuran (THF, 100 ml) in an oven-dried 250 ml two-necked round-bottomed flask. The reaction system was degassed with nitrogen. To this clarified solution 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCl, 4.02 g, 20.9 mmol) and N-methylmorpholine (NMM, 2.3 ml, 20.9 mmol) were added sequentially. The reaction mixture was stirred for 10 min at room temperature under nitrogen protection. Subsequently, dimethylamine solution (Me2NH, 13.06 ml, 2N, 25.5 mmol) was slowly added dropwise and the reaction was continued to be stirred for 16 h at room temperature. The progress of the reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, the reaction mixture was quenched with water and extracted with ethyl acetate (3 x 100 ml). The organic phases were combined, washed with saturated saline and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure to obtain the crude product, which was purified by column chromatography (silica gel 100-200 mesh, 2% methanol/dichloromethane) to afford the target compound [198] (2.62 g, 75%) as a white solid. Electrospray mass spectrometry (ESTMS): 185 (M++1).