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Step 3: Synthesis of 1-(2-methylpyridin-4-yl)ethanone (46d) To a stirred tetrahydrofuran (THF) solution (520 mL) of N-methoxy-N,2-dimethylisonicotinamide (46c) (26 g, 144.28 mmol) under nitrogen protection, methyl lithium (MeLi, 6.342 g, 288.562 mmol, 1M THF solution) was slowly added at -78 °C. The reaction mixture was gradually warmed to room temperature over a period of 1 h, followed by quenching the reaction with saturated ammonium chloride (NH4Cl) solution at 0 °C. The reaction mixture was extracted with ethyl acetate, the organic layers were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude product was purified by column chromatography to afford 1-(2-methylpyridin-4-yl)ethanone (46d) (11 g, 56.4% yield) as a slightly red viscous liquid. 1H NMR (CDCl3) δ: 8.61-8.59 (d, 1H), 7.51-7.45 (d, 1H), 7.45-7.44 (m, 1H), 4.05-4.02 (s, 3H). MS (ES+): 136.1 (M + 1).