2-Amino-5-chloro-3-iodopyridine

Uses

2-Amino-5-chloro-3-iodopyridine is a useful synthetic intermediate. It was used in the rational design of highly selective spleen tyrosine kinase inhibitors. It was also used to synthesize azaindole derivatives with antibacterial and antifungal activities.

Synthesis

GENERAL STEPS: 24,150 mL of a solvent mixture of tetrahydrofuran and 50 L of ethylene dichloride were added to an 8000 mL reactor, a plug-in thermometer was installed and a mechanical stirrer was started. Subsequently, 6037.5 g of 2-amino-5-chloropyridine and 18528 g of N-iodosuccinimide were added to the reactor. The reaction mixture was stirred continuously at 53 °C for 7 hours. The progress of the reaction was monitored by thin layer chromatography (TLC) and gas chromatography (GC) to confirm the complete reaction of 2-amino-5-chloropyridine. Upon completion of the reaction, the solvent was removed using a rotary evaporator to give the crude product. The crude product was recrystallized by a solvent mixture of ethyl acetate and ethanol to obtain purified 2-amino-3-iodo-5-chloropyridine. The product was dried and the calculated yield was 90.10% and the purity was 98.2% by GC.

References

[1] Patent: CN104744353, 2017, B. Location in patent: Paragraph 0017-0031
[2] Organic and Biomolecular Chemistry, 2014, vol. 12, # 2, p. 307 - 315
[3] Patent: US2014/18533, 2014, A1. Location in patent: Paragraph 0074; 0075
[4] Patent: WO2011/73263, 2011, A1. Location in patent: Page/Page column 88-89
[5] Patent: WO2005/95400, 2005, A1. Location in patent: Page/Page column 345-346