Uses
1,3-Dimethyl-1H-pyrazole-4-carbaldehyde is used in preparation of the inhibitors of SARM1 for the treatment or preventing of axonal degeneration.
Synthesis
GENERAL PROCEDURE: Phosphorus oxychloride (POCl3, 0.1 mol) was slowly added dropwise to N,N-dimethylformamide (DMF, 20 mL) at 0°C. The mixture was cooled to -20°C and N-alkylhydrazone (0.05 mol) was added dropwise to DMF (10 mL) at that temperature. After 1 hour of reaction, the mixture was cooled to -20 °C and a solution of N-alkylhydrazone (0.05 mol) in DMF (10 mL) was slowly added dropwise at this temperature. The reaction was kept at -20 °C with stirring for 3 h. The temperature was then increased to 80 °C with continued stirring for 2 h. The reaction was then carried out at -20 °C with stirring. After completion of the reaction, the mixture was cooled to room temperature and carefully poured into ice (100 g). The mixture was adjusted to alkaline (pH=9-10) with 30% aqueous sodium hydroxide solution. The product was extracted with chloroform (CHCl3, 3 x 200 mL). The organic phases were combined and dried over anhydrous sodium sulfate (Na2SO4). The solvent was removed by concentration under reduced pressure and the residue was purified by vacuum distillation.
References
[1] Chemistry of Heterocyclic Compounds, 2011, vol. 47, # 8, p. 1048 - 1049
[2] Tetrahedron Letters, 2014, vol. 55, # 14, p. 2187 - 2189
