Synthesis
The general procedure for the synthesis of 2-amino-4-chloro-6-methylpyridine from 2-amino-4,6-dichloropyridine and trimethylcyclotriboroxane is as follows: to a 10% aqueous solution of dioxane (0.1 M) were added sequentially 2-amino-4,6-dichloropyridine (1.0 eq.), trimethylcyclotriboroxane (1.5 eq.), tetrakis(triphenylphosphine)palladium (0.10 eq.) and potassium carbonate (3.0 eq.). The reaction mixture was heated to 120 °C in an oil bath with continuous stirring for 18 hours. Upon completion of the reaction, it was cooled to room temperature (note: not all ingredients were completely consumed). The reaction mixture was extracted with ethyl acetate and the organic phase was dried over anhydrous sodium sulfate and subsequently concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using 5% methanol/dichloromethane as eluent, resulting in an off-white 2-amino-4-chloro-6-methylpyridine solid in 23% yield.LCMS analysis showed a molecular ion peak (m/z) of 143 (MH+) for the target compound with a retention time (Rt) of 1.11 min on the liquid chromatogram.
