Synthesis
Step 1. Synthesis of 2-bromo-3-methoxyaniline (C23)
Iron powder (1.94 g, 34 mmol) was added to an ethanol solution (18 mL) of 2-bromo-1-methoxy-3-nitrobenzene (2.50 g, 10.77 mmol) followed by concentrated hydrochloric acid (1 mL). The reaction mixture was heated to reflux for 1.5 hours. Upon completion of the reaction, the mixture was cooled to room temperature, filtered through a pad of diatomaceous earth, and the filtrate was concentrated under vacuum to afford the title compound 2-bromo-3-methoxyaniline as a solid.
Yield: 2.57 g (10.77 mmol, 100%).
LCMS m/z: 202.1 [M + H]+.
1H NMR (400 MHz, CD3OD) δ: 3.77 (s, 3H), 6.30 (d, J = 8.0 Hz, 1H), 6.43 (d, J = 8.0 Hz, 1H), 6.98 (dd, J = 8.0, 8.0 Hz, 1H).
References
[1] Patent: US2012/252758, 2012, A1. Location in patent: Page/Page column 27
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 23, p. 9287 - 9295
[3] Patent: US2007/78147, 2007, A1. Location in patent: Page/Page column 67
[4] Patent: WO2018/13774, 2018, A1. Location in patent: Page/Page column 318
[5] Patent: EP3239143, 2017, A2. Location in patent: Paragraph 0441
