Synthesis
Step 4: Synthesis of 6-bromo-2-chloroquinazoline. 6-Bromo-2(1H)-quinazolinone (6.0 g, 26.7 mmol) was dissolved in phosphorus oxychloride (POCl3, 80 mL) and the reaction was carried out by refluxing at 110 °C for 5 hours. The reaction progress was monitored by liquid chromatography-mass spectrometry (LCMS) to confirm the completion of the reaction. At the end of the reaction, most of the phosphorous trichloride was evaporated under reduced pressure and the residue was added slowly dropwise to ice water (500 mL). The precipitated yellow solid product was collected by filtration to afford 6-bromo-2-chloroquinazoline (3.5 g, 54% yield). Mass spectrometry (electrospray positive ion mode, ES+) analysis resulted in a theoretical molecular weight of 242 for C8H4BrClN2 and a measured value of 243,245 [M+H]+.
References
[1] Patent: US2015/119405, 2015, A1. Location in patent: Paragraph 0446; 0455; 0456
[2] Patent: WO2014/11900, 2014, A2. Location in patent: Page/Page column 37; 38
[3] Patent: US2015/197519, 2015, A1. Location in patent: Paragraph 0131; 0132
[4] Patent: US9695165, 2017, B2. Location in patent: Page/Page column 38; 39
