Synthesis
Anhydrous DMF (1.5 mL) was added slowly and dropwise to the suspension formed by stirring 5-isoquinolinesulfonic acid (28.3 g, 135 mmol) with thionyl chloride (150 mL, 2.06 mol) at room temperature and under nitrogen protection. The reaction mixture was heated to reflux and maintained for 2.5 hours. After completion of the reaction, it was cooled to room temperature and subsequently concentrated under reduced pressure to give a light yellow powder. The powder was suspended in anhydrous dichloromethane (200 mL), sonicated, filtered, and dried under reduced pressure at 40 °C to yield a final isoquinoline-5-sulfonyl chloride hydrochloride 29.2 g (111 mmol, 82% yield). The structure of the product was confirmed by 1H NMR (TFA-d): δ 8.48 (t, J = 7.9 Hz, 1H), 9.13-9.14 (m, 2H), 9.29 (d, J = 7.9 Hz, 1H), 9.57 (d, J = 7.0 Hz, 1H), 10.26 (s, 1H).
References
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[2] Journal of Medicinal Chemistry, 1989, vol. 32, # 1, p. 42 - 46
[3] Journal of Medicinal Chemistry, 1989, vol. 32, # 1, p. 46 - 50
[4] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 9, p. 5277 - 5284
[5] Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 5922 - 5933
