Chemical Properties
Off-white powder or chunks solid
Uses
3-Amino-isonicotinic Acid Ethyl Ester acts as a reagent for the synthetic preparation of heteroaryl compounds as PDE-10 inhibitors useful in treatment and prevention of CNS, metabolic and other diseases. Also in the design and evaluation of 1,7-naphthyridones as novel KDM5 inhibitors.
Synthesis
To ethanol (20 mL) was added 3-aminoisonicotinic acid (1.4 g, 10 mmol) and stirred until completely dissolved. Concentrated sulfuric acid (2.94 g, 30 mmol) was added slowly and the reaction was heated to reflux for 20 hours. After completion of the reaction, ethanol was removed by distillation under reduced pressure. To the residue, water was added and the pH was adjusted to 8-9 with 2 N sodium hydroxide solution under cooling in an ice bath. the precipitated solid was filtered and dried to give ethyl 3-aminoisonicotinate (0.70 g, 42% yield). The filtrate was extracted with ethyl acetate, the organic phase was washed sequentially with water and saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure to give additional ethyl 3-aminoisonicotinate (0.30 g, 18% yield). The product was characterized by 1H-NMR (DMSO-d6): δ 1.30 (3H, t, J = 7.1 Hz), 4.28 (2H, q, J = 7.1 Hz), 6.66 (2H, br.s), 7.45 (1H, d, J = 5.2 Hz), 7.73 (1H, d, J = 5.2 Hz), 8.23 (1H, s).
References
[1] Australian Journal of Chemistry, 1993, vol. 46, # 7, p. 987 - 993
[2] Patent: EP1844768, 2007, A1. Location in patent: Page/Page column 29-30
[3] Journal of Organic Chemistry, 1952, vol. 17, p. 547,553
[4] Bulletin de la Societe Chimique de France, 1992, # 1, p. 79 - 84
[5] Journal of Medicinal Chemistry, 1993, vol. 36, # 18, p. 2676 - 2688
