反应详情

温度

132.5 °C

A mixture of 1-Bromo-7-cyclohexylsulfanyl-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester (686 mg, 1.57 mmol) and CuCN (279 mg, 3.13 mmol) in 3.6 mL of NMP was heated in a 130-135° C. oil bath for 3 h. Reaction mixture was diluted with CH2Cl2 (120 mL) and stirred at room temperature overnight. Then 100 mL of 0.5 N HCl aqueous solution was added and the resultant mixture was stirred vigorously for 30 min Two phases were separated and organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Crude residue was purified by silica gel chromatography, eluting with 5-60% EtOAc/hexanes, to provide the title compound 470 mg (1.22 mmol) in 78% yield. 1H NMR (200 MHz) CDCl3, δ in ppm: 12.36 (s, 1H), 8.27 (d, J=8.8 Hz, 1H), 8.01 (s, 1H), 7.68 (d, J=8.8 Hz, 1H), 4.50 (t, J=6.8 Hz, 2H), 3.50 (br m, 1H), 2.10 (m, 2H), 1.87-1.39 (m, 12H), 1.00 (t, J=7.2 Hz, 3H).

1. customReaction mixture
2. customwere separated
3. washorganic layer was washed with brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customCrude residue was purified by silica gel chromatography
8. washeluting with 5-60% EtOAc/hexanes