5-chloro-1-Methyl-4-nitro-1H-pyrazole

Application

5-Chloro-1-methyl-4-nitropyrazole can be used as an organic synthesis intermediate and a pharmaceutical intermediate in laboratory research and development processes and in the synthesis of pharmaceutical chemicals.

Synthesis

Example 1: General procedure for the synthesis of 5-chloro-1-methyl-4-nitro-1H-pyrazole from 1-methyl-4-nitropyrazole (a) Synthesis of 5-chloro-1-methyl-4-nitro-1H-pyrazole A THF solution of lithium bis(trimethylsilyl)amide (1.0 M, 65 mL, 65 mmol) was slowly added dropwise to a solution of dichloromethane (120 mL) containing 1-methyl-4-nitro-1H-pyrazole (5.50 g, 43.3 mmol) and hexachloroethane (10.54 g, 44.5 mmol) at 25 °C. The reaction mixture was stirred continuously at 25 °C for 60 min, followed by quenching the reaction with 1 mL of water. The mixture was concentrated to dryness and the residue was washed sequentially with 50 mL of water, saturated NaHCO3 solution (2 x 30 mL) and 30 mL of brine, and finally dried under vacuum to give 6.50 g of the target product in 93% yield. MS(ESI) m/z: 162.0 [M+H]+. 1H NMR (500MHz, CDCl3) δ: 8.15 (s, 1H), 3.92 (s, 3H).

References

[1] Patent: WO2016/90380, 2016, A1. Location in patent: Paragraph 0021
[2] Patent: US2015/57265, 2015, A1. Location in patent: Paragraph 0714
[3] Patent: CN108373476, 2018, A. Location in patent: Paragraph 0237-0239; 0242; 0243; 0290; 0294
[4] Patent: US2011/251176, 2011, A1. Location in patent: Page/Page column 103
[5] Patent: US2013/79321, 2013, A1. Location in patent: Paragraph 0177; 0178; 0179