General procedure for the synthesis of 5-(trifluoromethyl)pyridazin-3-amine from 3-chloro-5-(trifluoromethyl)pyridazine: Intermediate 47: Preparation of 5-(trifluoromethyl)pyridazin-3-amine. 3-Chloro-5-(trifluoromethyl)pyridazine (236 mg, 1.2 mmol) and ammonium hydroxide (0.05 mL, 1.2 mmol) were dissolved in THF (2 mL), and the solution was placed in a microwave reactor and heated at 100 °C for 1 hr. Subsequently, additional ammonium hydroxide (0.05 mL, 1.2 mmol) was added and the reaction mixture was continued to be heated in a microwave reactor at 100 °C for 1 hour. Ammonium hydroxide (0.05 mL, 1.2 mmol) was added again and the reaction mixture was heated in a microwave reactor at 100 °C for another 8 hours. After completion of the reaction, the mixture was diluted with water (50 mL) and extracted with dichloromethane (50 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuum to give 5-(trifluoromethyl)pyridazin-3-amine (150 mg, 0.92 mmol, 71% yield) as an orange powder, which was used in subsequent steps without further purification. Mass spectrometry method 2: retention time (RT): 0.79 min, m/z 163.8 [M + H]+.
