Hydrochloric Acid → HCID 24968869, compound

Participants

Reaction Steps

To a solution of N-tert-butyl-2-[3-(4-fluoro-3-methoxyphenyl)-7-hydroxy-1-oxo-1H-isoquinolin-2-yl]acetamide (INTERMEDIATE III.1) (25 mg, 0.063 mmol) in anhydrous acetonitrile (5 mL) were added K2CO3 (26 mg, 0.189 mmol) and 1-bromo-3-chloropropane (6.2 uL, 0.63 mmol). The reaction mixture was heated at reflux temperature for 16 h. Pyrrolidine (53 uL, 0.63 mmol) and additional K2CO3 (26 mg, 0.189 mmol) were added and the reaction mixture was heated at reflux temperature for 48 h. The reaction mixture was filtered and the filtrate concentrated in vacuo. The crude residue was purified by preparative HPLC to afford N-tert-butyl-2-[3-(4-fluoro-3-methoxyphenyl)-1-oxo-7-(3-pyrrolidin-1-ylpropoxy)-1H-isoquinolin-2-yl]acetamide (EXAMPLE 15) hydrochloride salt (4.4 mg, 0.008 mmol, 13%) as an HCl salt.

Provenance & Evidence