Hydrochloric Acid → HCID 89813167, compound

Participants

Reaction Conditions

Reaction Steps

A 20-mL scintillation vial was charged with 1-bromo-4-hydroxy-7-(4-fluoro-2-chloro-phenoxy)-isoquinoline-3-carboxylic acid ethyl ester (340 mg, 0.77 mmol), CuCN (138 mg, 1.54 mmol) and NMP (1.8 mL). It was filled with N2 gas and close-capped. The mixture was stirred in a 130° C. oil bath for 3 h. Reaction mixture was diluted with CH2Cl2 (100 mL) and stirred at room temperature for 3 days. To the mixture was added 100 mL of 0.5 N HCl aq. solution. It was stirred vigorously for 3 min. Two phases were separated. Organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Crude product was purified by silica gel chromatography, eluting with 5-50% EtOAc/hexanes to provide the title compound 231 mg (0.60 mmol) in 78% yield. 1H NMR (200 MHz) in CDCl3, δ ppm: 12.42 (s, 1H), 8.45 (d, J=8.8 Hz, 1H), 7.54 (dd, J=9.2, 2.6 Hz, 1H), 7.40-7.10 (m, 4H), 4.58 (q, J=7.0 Hz, 2H), 1.51 (t, J=7.0 Hz, 3H).

Provenance & Evidence