2-Methoxy-3-pyridinecarboxaldehyde

Chemical Properties

Colorless to yellow liquid

Uses

2-Methoxy-3-pyridinecarboxaldehyde may be used to synthesize the following:

• ethyl 5-amino-4-(2-methoxy-3-pyridyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinoline-3-carboxylate, a potent AChE inhibitor
• N-hydroxy-2-pyridinone-based arylsulfone containing a Zn-binding group (ZBG) as MMP-2/-9 inhibitor

Synthesis Reference(s)

Tetrahedron Letters, 29, p. 773, 1988 DOI: 10.1016/S0040-4039(00)80206-3

Synthesis

124-41-4

36404-88-3

71255-09-9

Sodium metal (0.35 g, 15.0 mmol) was slowly added to dry methanol (6 mL) at 0 °C and stirred until completely dissolved. Subsequently, a solution of anhydrous methanol (2 mL) of 2-chloro-3-pyridinecarboxaldehyde (0.708 g, 5.0 mmol) was added to the reaction system via syringe. The reaction mixture was heated to reflux temperature and maintained for 5 hours. Upon completion of the reaction, the mixture was cooled to room temperature and the solvent was subsequently evaporated under reduced pressure. The residue was dissolved in water (10 mL), neutralized with dilute hydrochloric acid and extracted with ether (3 x 10 mL). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by fast column chromatography (eluent: petroleum ether/ethyl acetate, 4:1) to afford the target compound 2-methoxy-3-pyridine aldehyde (0.473 g, 69% yield) as a colorless oil.1H NMR (300 MHz, CDCl3) δ 10.34 (d, J = 0.8 Hz, 1H), 8.36 (dd, J = 4.9, 2.1 Hz, 1H), 8.09 (dd, J = 7.4, 2.1 Hz, 1H), 7.00 (ddd, J = 7.4, 4.9, 0.8 Hz, 1H), 4.07 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 189.1, 164.4, 152.8, 137.6, 118.8, 117.3, 54.0.

References

[1] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 14, p. 3933 - 3937
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1990, # 9, p. 2409 - 2415