4-chloro-N-methoxy-N-methylpicolinamide

Synthesis

N,O-dimethylhydroxylamine hydrochloride (4.6 g, 47.61 mmol) was dissolved in DMF (50 mL) at 0 °C, followed by the addition of DIPEA (16.9 mL, 95.23 mmol) and the mixture was stirred for 10 min. Next, 4-chloropyridine-2-carboxylic acid (5.0 g, 31.74 mmol) and HATU (17.8 g, 47.61 mmol) were added and the reaction mixture was stirred for 16 hours at room temperature. After completion of the reaction, the solvent was removed by vacuum concentration and the product was purified by silica gel column chromatography using a hexane solution of 15-20% ethyl acetate as eluent to give 4-chloro-N-methoxy-N-methylpyridine-2-carboxamide (4.8 g, 96% yield). The product was characterized by 1H NMR (400 MHz, CDCl3): δ 3.37 (s, 3H), 3.72 (s, 3H), 7.35 (d, 1H), 7.63 (br s, 1H), 7.48 (d, 1H). the LCMS analysis showed a retention time of Rt = 2.30 min and a mass spectrum of m/z 201 [M + H]+ .

References

[1] Patent: WO2014/53967, 2014, A1. Location in patent: Page/Page column 151
[2] Patent: WO2015/138208, 2015, A1. Location in patent: Page/Page column 10-11