5-Amino-2-chloropyridine-4-carboxylic acid

Chemical Properties

Brown powder

Uses

3-Amino-6-chloroisonicotinic Acid is a useful synthetic intermediate. It can be used to prepare inhibitors of the EGFr and c-erbB-2. It can also be used to synthesise modulators of GHSr-1a for the treatment of type II diabetes and obesity.

Synthesis

The general procedure for the synthesis of 5-amino-2-chloropyridine-4-carboxylic acid from 5-tert-butoxycarbonylamino-2-chloropyridine-4-carboxylic acid is as follows: 5-[N-(tert-butoxycarbonyl)amino]-2-chloropyridine-4-carboxylic acid (1.91 g, 7 mmol) was suspended in dichloromethane (200 mL), and trifluoroacetic acid was added slowly dropwise with stirring until the solution became homogeneous (about 5%) 12 mL). The reaction mixture was stirred overnight at room temperature. Subsequently, the reaction mixture was extracted with dilute aqueous ammonia solution and the aqueous phase was acidified with dilute hydrochloric acid to precipitate 5-amino-2-chloropyridine-4-carboxylic acid precipitate (1.05 g, 87% yield). The product was characterized by nuclear magnetic resonance hydrogen spectroscopy (DMSO-d6): δ 9.01 (2H, multiple peaks), 8.03 (1H, single peak), 7.48 (1H, single peak).

References

[1] Journal of the Chemical Society - Perkin Transactions 1, 1996, # 18, p. 2221 - 2226
[2] Patent: US5654307, 1997, A
[3] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 11, p. 1401 - 1405
[4] Patent: WO2005/16926, 2005, A1. Location in patent: Page/Page column 115-116; 123
[5] ACS Medicinal Chemistry Letters, 2018, vol. 9, # 3, p. 256 - 261