100-51-6

1000896-40-1

The general procedure for the synthesis of 5-(benzyloxy)-1H-pyrazol-3-amine from benzyl alcohol was as follows: first, 5-amino-2H-pyrazol-3-ol (6.0 g, 60.6 mmol) was dissolved in dichloromethane (75 mL) and triphenylphosphine (19.06 g, 72.7 mmol) was added under stirring conditions. Subsequently, the reaction mixture was cooled to 5-10 °C and diisopropyl azodicarboxylate (14.31 mL, 72.7 mmol) was slowly added dropwise over 20 min, ensuring that the internal temperature was maintained below 15 °C. After dropwise addition, stirring was continued at 10 °C for 20 min. Next, benzyl alcohol (7.52 mL, 72.7 mmol) was added dropwise and stirred at 5-10 °C for 1 h. After that, the mixture was slowly warmed to room temperature and stirred continuously for 60 h under nitrogen protection. After completion of the reaction, the mixture was filtered and the filtrate was extracted with 1 M hydrochloric acid (3 x 15 mL) and the combined acid extracts were washed with dichloromethane (15 mL). The aqueous phase was alkalized with sodium bicarbonate (6.7 g) and then extracted with dichloromethane (2 x 40 mL). The organic phases were combined and concentrated by evaporation to give a brown oil, which was purified by silica gel column chromatography with a dichloromethane gradient of 0-3% methanol as eluent. The eluate containing the target product was collected and evaporated to give 5-benzyloxy-1H-pyrazol-3-amine (0.67 g, 6% yield). The product was confirmed by 1H NMR (300 MHz, CDCl3): δ 5.05 (s, 1H), 5.12 (s, 2H), 7.25-7.45 (m, 5H). Mass spectrometry analysis showed m/z 190 (MH+). In addition, 5-phenylmethoxy-2H-pyrazol-3-amine (i.e., 5-benzyloxy-1H-pyrazol-3-amine) can also be prepared with reference to the method of Example 72.