Synthesis
General procedure for the synthesis of pyrazine-2-iodo-3-carboxylic acid methyl ester from 3-aminopyrazine-2-carboxylic acid methyl ester: Referring to the method of Example 15, isopentyl nitrite (5.2 mL, 39 mmol) was slowly added to a suspension of 3-aminopyrazine-2-carboxylic acid methyl ester (1.9 g, 12 mmol) in diiodomethane (20 mL). Subsequently, the reaction mixture was heated to 85 °C and stirred continuously at 100 °C for 15 hours. After completion of the reaction, the mixture was cooled to room temperature and left to stand. The crude product was purified by silica gel column chromatography to afford 1.4 g of the target product 2-iodo-3-carboxylic acid methyl pyrazine as a light yellow solid in 44% yield. The product was characterized by 1H-NMR (500 MHz, CDCl3): δ 4.04 (s, 3H), 8.47 (d, J = 2.1 Hz, 1H), 8.56 (d, J = 2.1 Hz, 1H).
References
[1] Patent: EP1602647, 2005, A1. Location in patent: Page/Page column 58
[2] Patent: WO2018/118670, 2018, A1. Location in patent: Page/Page column 180; 181
