Synthesis
To a 2L three-necked flask was added 1000 mL of 2-pentanol, 50 g of 3-(2-chloropyrimidin-4-yl)-1-methylindole, 42 g of 4-fluoro-2-methoxy-5-nitroaniline, and 3.54 g of p-toluenesulfonic acid at room temperature. The reaction mixture was heated to 80 °C and kept stirring for 6 hours. Upon completion of the reaction, the mixture was cooled to 25 °C to 28 °C, followed by filtration to collect the solid product. The filter cake was washed with preheated 2-pentanol (50 °C) to remove impurities. The resulting solid product was dried in a vacuum oven to give 80.1 g of the final yellow solid product N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine in 99.0% yield.
References
[1] Patent: CN107188888, 2017, A. Location in patent: Paragraph 0061-0063
[2] European Journal of Medicinal Chemistry, 2017, vol. 135, p. 12 - 23
[3] Patent: WO2013/14448, 2013, A1. Location in patent: Page/Page column 138
[4] Journal of Medicinal Chemistry, 2014, vol. 57, # 20, p. 8249 - 8267
[5] Patent: CN107043369, 2017, A. Location in patent: Paragraph 0395; 0396; 0397; 0398
