General procedure for the synthesis of 1-chloro-7-methylisoquinoline from 1-hydroxy-7-methylisoquinoline: phosphorus oxychloride (POCl3, 10 mL) was mixed with 7-methylisoquinolin-1-ol (3.55 g, 22.3 mmol) under the protection of nitrogen and the reaction was carried out by heating and refluxing for 5 hours. Upon completion of the reaction, excess POCl3 was removed by distillation.The residue was quenched with ice water and subsequently extracted with dichloromethane (3×). The organic phases were combined and purified by fast silica gel column chromatography using a hexane solution of 10-25% ethyl acetate as eluent to afford the target product 1-chloro-7-methylisoquinoline (3.40 g, 85% yield). The product was characterized by 1H-NMR (300 MHz, CDCl3): δ 8.21 (d, 1H), 8.11 (s, 1H), 7.75 (d, 1H), 7.60 (d, 1H), 7.55 (d, 1H), 2.60 (s, 3H).
