3-Aminopyridine-2-carboxylic acid ethyl ester Chemical Properties

Melting point:

131-133 °C

Boiling point:

326.2±22.0 °C(Predicted)

Density 

1.192±0.06 g/cm3(Predicted)

storage temp. 

2-8°C(protect from light)

pka

2.79±0.10(Predicted)

Appearance

Off-white to light brown Solid

Safety Information

HS Code 

2933399990

3-Aminopyridine-2-carboxylic acid ethyl ester Usage And Synthesis

Uses

A synthetic intermediate for the synthesis of Kenpaullone derivatives, Cannabinoid receptor ligands, and nociceptive agents.

Synthesis

3-Aminopyridine-2-carboxylic acid (28 g, 200 mmol, 1.0 eq.) was suspended in ethanol (800 mL) at room temperature and bubbled through hydrogen chloride gas (HCl(g)) for 10 min, and the reaction mixture was transformed into a clarified yellow solution. The reaction mixture was heated to 100 °C and after stirring the reaction for 1 day, LCMS analysis showed that about 50% of the feedstock was unreacted. The reaction mixture was cooled to room temperature, bubbled again with hydrogen chloride gas (HCl(g)) for 10 minutes, and then reheated to 100 °C. The reaction mixture was then stirred for 1 day and the LCMS analysis showed that about 50% of the feedstock was unreacted. After continuing to stir the reaction for 1 day, LCMS analysis still showed that about 50% of the feedstock was unreacted. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to remove all solvent. The residue was resuspended in ethanol (800 mL) and bubbled through hydrogen chloride gas (HCl(g)) for 10 minutes. The resulting mixture was reacted at reflux in an oil bath at 100 °C for 1 day.LCMS analysis showed a conversion of about 70-75%. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to remove all solvents. The solid residue was dissolved in water (250 mL) and the pH was adjusted to 8-9 with saturated aqueous sodium carbonate (Na2CO3) for bursting. Gas production and formation of a white solid was observed. The suspension was filtered, the solid was washed with water and dried under vacuum at 65 °C to give ethyl 3-aminopyridine-2-carboxylate (22 g, 65% yield) as a white solid.LCMS (APCI, M++1) 167.0; 1H NMR (300 MHz, DMSO-d6) δ ppm 7.84 (dd, J=4.05,1.60 Hz, 1H), and 7.23-7.30 (m, 1H), 7.16-7.23 (m, 1H), 6.65 (br.s., 2H), 4.27 (q, J=7.10 Hz, 2H), 1.30 (t, J=7.06 Hz, 3H).

References

[1] Journal of Organic Chemistry, 2004, vol. 69, # 1, p. 54 - 61
[2] Patent: WO2016/97918, 2016, A1. Location in patent: Page/Page column 55
[3] Journal of Medicinal Chemistry, 2008, vol. 51, # 7, p. 2196 - 2207
[4] Journal of the Chemical Society, 1949, p. 3304,3310
[5] Journal of the Chemical Society, 1956, p. 1045,1053

3-Aminopyridine-2-carboxylic acid ethyl ester(27507-15-9)Related Product Information

• 3-Aminopyridine-2-carboxylic acid methyl ester
• 3-Aminopyridine
• (3-AMINO-PYRIDIN-2-YL)-METHANOL
• 3-Amino-2-pyridinecarboxylic acid
• 3-Aminopyridine-2-carboxylic acid ethyl ester
• 3-AMINO-PYRIDINE-2-CARBALDEHYDE
• ethyl 3-amino-5-bromopyridine-2-carboxylate
• ethyl 3-amino-5-chloropyridine-2-carboxylate
• AKOS 93356