5-chloro-1-methyl-1H-pyrazole-4-carbonitrile

5334-41-8

111493-52-8

Step 3: Synthesis of 5-chloro-1-methyl-1H-pyrazole-4-carbonitrile 5-Amino-1-methyl-1H-pyrazole-4-carbonitrile (12.1 g, 0.099 mol) was mixed with hydrochloric acid (72.6 ml, concentration: 35-37%) in deionized water (60.0 ml) and stirred at room temperature. The reaction mixture was cooled to 0 to 5°C and sodium nitrite solution (prepared from sodium nitrite (8.2 g, 0.119 mole) dissolved in deionized water (240 ml)) was added slowly. The reaction mixture was stirred at 0 to 5°C for 1-1.5 hours. Subsequently, urea solution (prepared from urea (1.2 g) dissolved in deionized water (6.0 ml)) was added slowly. Solid cuprous chloride (12.8 g, 0.129 mol) was added to the reaction mixture and stirred at 0 to 5°C for 3-4 hours. The reaction temperature was then raised to room temperature and stirring was continued for 12-18 hours. The reaction process was monitored by HPLC. Upon completion of the reaction, deionized water (120 ml) and 25% (w/v) aqueous sodium hydroxide solution (80.0 ml) were added to the mixture and the pH was adjusted to 3-3.5. 1,2-dichloroethane was added and stirred for 10-15 min at 45-50°C. The reaction was carried out at a temperature of 0 to 5°C for 10 min. Inorganic salts were removed by filtration through a hyflo bed. Separate the organic layer and extract the aqueous layer with 1,2-dichloroethane. The organic layers were combined, transferred to a reaction vessel and washed with 10% brine solution (50.0 ml). The organic layer was evaporated to give 5-chloro-1-methyl-1H-pyrazole-4-carbonitrile. Dry weight: 1.18 g Yield: 0.97 w/w (84%) HPLC purity: 93.34% Melting point: 55-60°C