Methyl 5-aminopyridine-3-carboxylate

Uses

It is used in organic synthesis and can be used as a starting material for the synthesis of 5-(hydroxymethyl)pyridine-3-ol.

Chemical Properties

Off-white solid

Application

Methyl 5-aminopyridine-3-carboxylate is mainly used as a pharmaceutical intermediate, pesticide intermediate, organic synthesis building block and scientific research reagent. Due to the reactivity of amino and ester groups, it is widely used in the synthesis of heterocyclic drugs, bioactive molecules and functional materials.

Synthesis

SOCl2 (10.4 g, 86.9 mmol) was slowly added dropwise to a stirred methanolic solution (100 mL) of 5-aminonicotinic acid (10.0 g, 72.5 mmol) at 0 °C. After gradually warming the reaction mixture to room temperature, the reaction was continued at reflux for 16 hours. After completion of the reaction, the mixture was cooled and concentrated under vacuum. The residue was diluted with deionized water (200 mL) and subsequently neutralized with aqueous NaHCO3 to pH=7. The aqueous phase mixture was extracted with dichloromethane (DCM, 100 mL x 2). The organic layers were combined, washed with saturated saline (100 mL × 2), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated to dryness under vacuum to give 9.5 g of methyl 5-aminopyridine-3-carboxylate as a white solid in 86% yield. The product was characterized by 1H NMR (DMSO-d6, 400 MHz): δ=8.24 (1H, d), 8.12 (1H, d), 7.42 (1H, dd), 5.65 (2H, brs), 3.84 (3H, s).

References

[1] Patent: WO2013/126608, 2013, A1. Location in patent: Paragraph 00492-00493
[2] Patent: WO2006/117549, 2006, A1. Location in patent: Page/Page column 97
[3] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 22, p. 6305 - 6310
[4] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 17, p. 6340 - 6350
[5] Chemistry - A European Journal, 2002, vol. 8, # 5, p. 1218 - 1226