Synthesis
General procedure for the synthesis of 2-amino-4-phenylpyridine from 2-amino-4-bromopyridine and phenylboronic acid: phenylboronic acid (141 mg, 1.156 mmol), 4-bromo-2-amino-pyridine (200 mg, 1.156 mmol) and PdCl2(dppf)-CH2Cl2 adduct (94 mg, 0.116 mmol) were suspended in a mixture of 1,2 -dimethoxyethane (3 mL) and 1 M aqueous sodium carbonate (3.47 mL, 3.47 mmol) in a mixed solvent. The reaction mixture was stirred at 90 °C for 5 h and subsequently cooled to room temperature. The reaction mixture was filtered through a diatomaceous earth pad and the filter cake was washed with dichloromethane (DCM). The filtrate was concentrated under reduced pressure to remove the solvent, and the resulting crude product was purified by silica gel column chromatography (Biotage 40M column) using 0-10% methanol/dichloromethane gradient elution to afford the target product 2-amino-4-phenylpyridine (195 mg, 1.146 mmol, 99% yield). The product structure was confirmed by 1H NMR (400 MHz, CDCl3) and UPLC-MS: 1H NMR δ 4.49 (dd, 2H), 6.69-6.78 (m, 1H), 6.90 (dd, 1H), 7.39-7.52 (m, 3H), 7.56-7.68 (m, 2H), 8.10-8.17 (m, 1H); UPLC-MS: tR = 0.42 min, m/z = 171 [M + H]+.
References
[1] Patent: US2009/203705, 2009, A1. Location in patent: Page/Page column 49
[2] Journal of Medicinal Chemistry, 2016, vol. 59, # 24, p. 11171 - 11181
[3] Patent: WO2017/141036, 2017, A1. Location in patent: Page/Page column 50
