842149-46-6

4-(7-bromo-4-chloro-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine (VI, 50 g, 0.14 mol) was used as a feedstock, suspended in THF (1 L) and cooled to an internal temperature of below -75 °C in a dry ice/acetone bath. Isopropylmagnesium chloride solution (225 mL, 2 M in ether, 0.45 mol) was added slowly to ensure that the reaction temperature was maintained below -70°C. After 10 minutes of reaction, trimethyl borate (54 mL, 0.48 mol) was added and the reaction continued for 1 hour in a dry ice/acetone bath. The cooling bath was then removed to allow the reaction mixture to gradually warm to room temperature. After 18 hours of reaction, the resulting yellow suspension was cooled to 0°C. A mixture of 30% hydrogen peroxide (250 mL) and 3N NaOH (100 mL) was slowly added, with the rate of addition controlled to keep the reaction temperature below 40°C. After removal of the ice bath, the reaction mixture was stirred vigorously at room temperature for 2 hours. Most of the organic solvent was removed by concentration under reduced pressure and the aqueous layer was acidified to pH 3 with 1 N HCl. The acidified suspension was stirred for 30 min and extracted by adding ethyl acetate (200 mL). After continued stirring for 1 h, the solid product was collected by filtration. The filter cake was washed sequentially with water, ethyl acetate, toluene and ethyl acetate until the washings were colorless. The solid was dried to constant weight to afford 35.9 g (88% yield) of the target compound (VII) as a light yellow solid, which could be used in subsequent reactions without further purification. Mass spectrum (ES+) m/z 281.3 ([M-H]+).

[1] Patent: WO2007/58850, 2007, A2. Location in patent: Page/Page column 40
[2] Patent: WO2007/58852, 2007, A2. Location in patent: Page/Page column 36
[3] Patent: WO2007/58879, 2007, A2. Location in patent: Page/Page column 34-35
[4] Patent: WO2005/11700, 2005, A1. Location in patent: Page/Page column 174