[Synthesis]
Chlorosulfonic acid (40 mL) was added slowly and dropwise to 1-chloroisoquinoline (9.92 g, 60.6 mmol) under nitrogen protection and at 0 °C under stirring. The reaction mixture was then heated at 155 °C for 24 hours. After completion of the reaction, the mixture was cooled to room temperature and slowly poured into ice (200 g). After cooling, the mixture was extracted with dichloromethane (300 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 13.6 g of 1-chloroisoquinoline-5-sulfonyl chloride as a white powder (51.9 mmol, 86% yield).1H NMR (CDCl3): δ 7.87 (t, J = 7.5 Hz, 1H), 8.52 (d, J = 6.2 Hz, 1H), 8.59 (d, J = 6.2 Hz, 1H ), 8.62 (d, J = 7.5 Hz, 1H), 8.82 (d, J = 7.5 Hz, 1H). Powdered 1-chloroisoquinoline-5-sulfonyl chloride (10.0 g, 38.2 mmol) was added batchwise to a stirred solution of tert-butyl (2-aminoethyl)-carbamate (7.33 g, 45.8 mmol) and triethylamine (10.7 mL, 76.4 mmol) in anhydrous dichloromethane (200 mL) at 0 °C. After the reaction mixture was stirred at room temperature for 4 h, it was concentrated and purified by silica gel column chromatography (elution gradient: dichloromethane solution in 0-5% methanol) to give 13.8 g of the product in foam form (35.8 mmol, 94% yield).ESIMS: m/z 386 [(M + H)+, 35Cl], 388 [(M + H)+, 37Cl]. Elemental analysis C16H20ClN3O4S: Calculated: C, 49.80; H, 5.22; N, 10.89; Measured: C, 49.70; H, 5.22; N, 10.72. |