2-Acetylamino-5-bromopyridine

Chemical Properties

White powder

Uses

2-Acetamido-5-bromopyridine is a chemical reagent used in the synthesis of novel Bcr-Abl inhibitors with diacylated piperazine felxible linkers. Also used to produce hetero-monocyclic derivatives as even more potent inhibitors of BCR-ABL.

Synthesis

2-Amino-5-bromopyridine (86.50 g, 500 mmol), acetic anhydride (153 g, 1500 mmol) and 850 mL of acetic acid were added to a 2000 mL single-necked round-bottomed flask with a magnetic stirrer turned on. The reaction mixture was stirred at 100 °C for 9 hours. After confirming the complete reaction of 2-amino-5-bromopyridine by thin layer chromatography (TLC) and gas chromatography (GC) monitoring, water was added to the reaction solution. Subsequently, the reaction was filtrated and the filter cake was washed with a solvent mixture of ethyl acetate and n-hexane (1:4, v/v) to obtain the pure product 2-acetamido-5-bromopyridine. The filtrate was extracted with ethyl acetate, and the extract was concentrated by rotary evaporation to obtain the crude product, which was recrystallized with a mixed solvent of ethyl acetate and hexane (1:4, v/v) and further purified to obtain 2-acetamido-5-bromopyridine. The product was dried and the calculated yield was 75.40%, and the purity was 99.68% as determined by high performance liquid chromatography (HPLC).

References

[1] Patent: CN103601745, 2017, B. Location in patent: Paragraph 0029; 0030
[2] Tetrahedron Letters, 2002, vol. 43, # 17, p. 3121 - 3123
[3] Patent: WO2011/130628, 2011, A1. Location in patent: Page/Page column 205
[4] Patent: US2013/102595, 2013, A1. Location in patent: Paragraph 0480; 0481
[5] Patent: JP2015/187145, 2015, A. Location in patent: Paragraph 0414