Synthesis
General procedure for the synthesis of 3-(4-fluoropropyl)-1H-pyrazole-4-carbaldehyde from 2-(1-(4-fluorophenyl)ethylidene)hydrazine-1-carboxamide and N,N-dimethylformamide: Phosphorochloride (2.1 mL, 23 mmol) was slowly added dropwise to N,N-dimethylformamide (4.4 mL, 57 mmol) at 0 °C. The reaction mixture was stirred at 0 °C for 30 min, then brought to room temperature and continued stirring for 30 min. Subsequently, the reaction mixture was cooled in an ice/water bath and 2-(1-(4-fluorophenyl)ethylidene)hydrazine-1-carboxamide (1.96 g, 10 mmol) was slowly added, controlling the temperature not to exceed 50 °C. After the addition was completed, the reaction system was heated to 80 °C and stirred at this temperature for 2 hours. After completion of the reaction, the mixture was poured into ice (15 g) and the pH was adjusted to 10 with 5N NaOH solution and stirred for 2 hours. Subsequently, the reaction solution was acidified with concentrated hydrochloric acid and stirring was continued for 4 hours. The precipitated solid was collected by filtration, washed with a small amount of water and dried under high vacuum to give the target product 3-(4-fluoropropyl)-1H-pyrazole-4-carbaldehyde (1.5 g, 79% yield).
References
[1] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 18, p. 4932 - 4935
[2] Russian Journal of General Chemistry, 2005, vol. 75, # 5, p. 782 - 789
[3] Patent: WO2013/22766, 2013, A1. Location in patent: Page/Page column 87
[4] European Journal of Medicinal Chemistry, 2017, vol. 133, p. 36 - 49
[5] Journal of Fluorine Chemistry, 2016, vol. 183, p. 59 - 68
