General procedure for the synthesis of 5-bromo-4-pyrazinamine from 4-aminopyridazine: pyridazin-4-amine (1.18 g, 12.41 mmol) was dissolved in acetic acid (2.5 mL) in a water bath at room temperature. Dibromide (0.638 mL, 12.41 mmol) was added slowly and dropwise. After 1 hour of reaction, the reaction was neutralized by the addition of 10N NaOH solution, followed by extraction with dichloromethane (3 times). The organic phases were combined, dried over sodium sulfate and subsequently concentrated under vacuum. The crude product was dissolved in a small amount of dichloromethane and purified by passing through a 40 g silica gel column using a 0-15% dichloromethane/methanol gradient elution for 40 min. Fractions containing the target product were collected and combined and dried under vacuum to give 3-bromopyridazin-4-amine (0.1 g, 0.575 mmol, 4.63% yield, first elution) and 5-bromopyridazin-4-amine (0.12 g, 0.690 mmol, 5.56% yield, second elution), respectively. The 1H NMR (400 MHz, DMSO-d6) data of the product 5-bromopyridazin-4-amine were as follows: δ 8.75 (s, 1H), 8.55 (s, 1H), 6.72-6.79 (m, 2H).
