反应详情

温度

70 °C

A mixture of 4-(3,4-bis{[2-(methyloxy)ethyl]oxy}phenyl)-3-methyl-1H-pyrazol-5-amine (114 mg, 0.36 mmol), 3-chloro-4-hydroxybenzaldehyde (117 mg, 0.75 mmol) and trifluoroacetic acid (3 mL) was heated at 70° C. for 18 hours. Then the reaction mixture was concentrated, dissolved in 10 mL of N,N-dimethylformamide and purified by preparatory HPLC (Shimadzu LC-8A HPLC, Waters Xterra C18 30 mm×100 mm column, acetonitrile-water-trifluoroacetic eluent). After concentration then lyophillization of the pure fractions a yellow powder was obtained. It was dissolved in 4 mL of 1:1 methanol: 4M hydrogen chloride in dioxane, and evaporated to dryness (repeated three times) to give 2-chloro-4-(1-methyl-7,8-bis{[2-(methyloxy)ethyl]oxy}-3H-pyrazolo[3,4-c]isoquinolin-5-yl)phenol hydrochloride salt (84 mg, 0.17 mmol, 47% yield) 1H NMR (400 MHz, d6-DMSO): 10.65 (b, 1H), 7.68-7.67 (b, 2H), 7.53-7.48 (m, 2H), 7.16-7.14 (d, 1H), 4.45-4.43 (m, 2H), 4.09-4.07 (m, 2H), 3.80-3.78 (m, 2H), 3.68-3.66 (m, 2H), 3.36 (s, 3H), 3.30 (s, 3H), 2.81 (s, 3H); MS (EI) for C23H24ClN3O5: 458 (MH+).

1. concentrationThen the reaction mixture was concentrated
2. dissolutiondissolved in 10 mL of N,N-dimethylformamide
3. custompurified by preparatory HPLC (Shimadzu LC-8A HPLC, Waters Xterra C18 30 mm×100 mm column, acetonitrile-water-trifluoroacetic eluent)
4. concentrationAfter concentration
5. customlyophillization of the pure fractions a yellow powder was obtained
6. custom4M hydrogen chloride in dioxane, and evaporated to dryness (repeated three times)