Uses
An Isonicotinic Acid (I821760) derivative. Used in the preparation of 4,5-dihydro-1H-pyrazole derivatives as cholesterol 24 hydroxylase inhibitors for prevention and/or treatment of neurodegenerative disease.
Uses
3-Methyl-4-pyridinecarboxylic acid can be used in the preparation of 4,5-dihydro-1H-pyrazole derivatives as cholesterol 24 hydroxylase inhibitors for prevention and/or treatment of neurodegenerative disease.
Synthesis
The general procedure for the synthesis of 3-methyl-4-pyridinecarboxylic acid from 3,4-dimethylpyridine was as follows: 3,4-dimethylpyridine (119.30 g, 0.28 mol) was dissolved in diphenyl ether (150 mL) and heated to 150-170 °C, followed by the slow addition of selenium dioxide (62 g, 0.56 mol). Selenium dioxide was added in batches over a period of 1 hour. The reaction mixture was heated to 180 °C and maintained at this temperature for 1 hour. Upon completion of the reaction, the mixture was filtered while hot and the collected precipitate was washed with boiling water (3 x 300 mL). The filtrates were combined and extracted with chloroform (3 x 300 mL). The aqueous phase was evaporated to dryness and the resulting crude product was recrystallized from ethanol (450 mL) to give pure 3-methyl-4-pyridinecarboxylic acid (18 g, 47% yield) with a melting point of 220-222°C (Literature value: J. Chem. Soc., Perkin Trans. 1, 1984, 1501-1505, melting point 232°C).1H NMR (300 MHz, DMSO-d6) δ 8.59 (s, 1H), 8.04 (s, 1H), 8.47 (d, J = 4.8 Hz, 1H), 7.69 (d, J = 4.8 Hz, 1H), 2.48 (s, 3H).
References
[1] Journal of Medicinal Chemistry, 2012, vol. 55, # 4, p. 1682 - 1697
[2] Patent: US2014/18360, 2014, A1. Location in patent: Paragraph 0152
[3] Journal of Medicinal Chemistry, 2012, vol. 55, # 22, p. 10118 - 10129
[4] Patent: US5952343, 1999, A
[5] Patent: US5461154, 1995, A
