Sodium bis(trimethylsilyl)amide → 1-(5-(6-Amino-2-methylpyrimidin-4-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone

Participants

Reaction Steps

A mixture of 6-(5-(1-ethoxyvinyl)-2-fluoropyridin-3-yl)-2-methylpyrimidin-4-amine (208 mg, 0.76 mmol) and 5-fluoro-6-methoxypyridin-3-amine (162 mg, 1.14 mmol) in 1.5 mL of THF at 0° C. was added sodium bis(trimethylsilyl)amide (1 M in THF) (2.28 mL, 2.28 mmol) dropwise at 0° C. and the dark red solution was stirred at this temperature for 30 min. It was quenched with 4 mL of 0.5N HCl and stirred for 10 min. The mixture was basified with 1 N NaOH to pH of 8 and stirred with 10 mL of EtOAc for 5 min. The precipitated brown solid was filtered, washed with 2×2 mL of water followed by 2×2 mL of EtOAc. The brown solid was dried in a vacuum oven at 45° C. for 18 h to give 1-(5-(6-amino-2-methylpyrimidin-4-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (90 mg, 32% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.93 (s, 1H), 8.90 (s, 1H), 8.50 (s, 1H), 8.37 (s, 1H), 8.24 (s, 1H), 7.10 (br., 2H), 6.93 (s, 1H), 3.95 (s, 3H), 2.60 (s, 3H), 1.58 (s, 3H). m/z (ESI, positive ion) 369.0 (M+H)+.

Provenance & Evidence