Synthesis
To an ethanol (600 mL) suspension of tert-butylhydrazine hydrochloride (15.0 g, 120.4 mmol) was added triethylamine (16.8 mL, 120.4 mmol). The mixture was stirred for 60 minutes until the tert-butylhydrazine was completely dissolved. Subsequently, ethoxymethylene malononitrile (14.7 g, 120.4 mmol) was added in batches and the reaction mixture was heated to 80 °C and stirred at this temperature overnight. After completion of the reaction, the mixture was concentrated to dryness under reduced pressure. The obtained residue was dissolved in ethyl acetate (EtOAc), the organic layer was washed with water, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. Finally, the resulting solid was recrystallized in dichloromethane (DCM) to afford 5-amino-4-cyano-1-tert-butylpyrazole (18.6 g, 113.4 mmol, 94% yield) as a light yellow solid.LC-MS (ES+, Method 1): 1.36 min, m/z 165.1 [M + H]+.
References
[1] MedChemComm, 2017, vol. 8, # 3, p. 640 - 646
[2] Patent: WO2017/46604, 2017, A1. Location in patent: Paragraph 00228
[3] Organic Letters, 2012, vol. 14, # 15, p. 3906 - 3908
[4] Patent: CN106008527, 2016, A. Location in patent: Paragraph 0048; 0049; 0050; 0051
[5] European Journal of Organic Chemistry, 2008, # 19, p. 3377 - 3381
