[Synthesis]
GENERAL METHOD: Copper(II) acetate (0.550 g, 3.03 mmol) was added to a solution of 2-amino-5-chloropyridine (1.22 mmol) and pyridine (0.34 mL, 4.24 mmol) in dioxane (15 mL). The mixture was stirred for 15 min, methylboronic acid (0.181 g, 3.03 mmol) was added and the reaction was refluxed until the 2-amino-5-chloropyridine was completely consumed (reaction time monitored by TLC analysis, 1.5-18 h). The reaction mixture was allowed to cool to room temperature, filtered through diatomaceous earth and the solvent was evaporated. The residue was purified by fast chromatography (elution gradient: 0→50% ethyl acetate/hexane) to give 5-chloro-N-methylpyridin-2-amine (162).
Preparation of 5-chloro-N-methylpyridin-2-amine (162): compound 162 was prepared from 2-amino-5-chloropyridine (160) according to the above method F. 73 mg of brown powder was obtained in 42% yield.
1H NMR (500 MHz, CDCl3) δ 2.90 (s, 3H), 4.79 (br s, 1H), 6.33 (d, J = 8.9 Hz, 1H), 7.38 (dd, J = 2.6, 8.9 Hz, 1H), 8.02 (d, J = 2.6 Hz, 1H).
13C NMR (126 MHz, CDCl3) δ 29.22, 106.90, 119.44, 137.27, 146.26, 157.88.
LC-MS (M + H+) calculated value C6H7ClN2 143, measured value 143. |