APE1/Ref-1 Redox Inhibitor APX3330 → 4-Methyl-2,6-dimethoxyphenol

Beteiligte Stoffe

Reaktionsschritte

The second step in the synthesis of E3330 is the most problematic, where the Ullmann-type methanolysis of 2,3,6-tribromo-4-methylphenol (5) results in multiple reduction byproducts that are not disclosed in the literature.13,14 The optimized Ullmann conditions in our hands result in a mixture of 4-methyl-2,3,6-trimethoxyphenol (11, 75-85%), 2,6-dimethoxy-4-methylphenol (12, 10-15%), and 2,5-dimethoxy-4-methylphenol (13, 5-10%). (Scheme 2) The resulting phenols are alkylated to generate 2,3,4,5-tetramethoxytoluene (6) and the two trimethoxytoluenes (14 and 15). The isolated yield is considerably lower than the observed conversion by NMR, and removal of the two reaction sideproducts is necessary because both lead to E3330 derivatives missing crucial methoxy substituents.

Herkunft & Nachweise