Synthesis
2,4-Dichloro-6-methylpyrimidine (5 g, 30.7 mmol) and phenylboronic acid (3.74 g, 30.7 mmol) were added with K2CO3 (12.72 g, 92 mmol) and Pd(PPh3)4 (1.06 g, 0.92 mmol) in a solvent mixture of toluene (150 ml) and methanol (35 ml). The reaction system was degassed with nitrogen and then heated at 90°C for overnight reaction. After completion of the reaction, it was cooled to room temperature and diluted by adding water (200 ml). The organic layer was separated and the aqueous layer was extracted with EtOAc (2 x 200 ml). The organic layers were combined, dried with anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by medium pressure liquid chromatography (MPLC, Biotage Horizon: FLASH 40+M) with the following elution procedure: 100% hexane (180 ml), followed by a gradient from 100% hexane up to a hexane solution of 20% EtOAc (1800 ml), and finally eluting with a hexane solution of 20% EtOAc (1000 ml) , yielding the target product 2-chloro-4-methyl-6-phenylpyrimidine (3 g, 48% yield). The structure of the product was confirmed by 1H NMR (CDCl3): δ 2.61 (s, 3H), 7.52 (m, 4H), 8.08 (m, 2H).
References
[1] Journal of Medicinal Chemistry, 2014, vol. 57, # 24, p. 10443 - 10454
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 21, p. 9120 - 9135,16
[3] Journal of Medicinal Chemistry, 2012, vol. 55, # 21, p. 9120 - 9135
[4] Patent: WO2011/25774, 2011, A1. Location in patent: Page/Page column 47
