Sodium hydride → Indole-3-Carboxaldehyde

Participants

Reaction Steps

Synthesis of the indoquinone-Naloxone linker involves multiple steps. Starting from 2-methyl-5-methoxyindole, alkylation on nitrogen with sodium hydride and t-butyl 4-bromobutanoate, followed by formylation provides the 3-formyl indole. After the nitration reaction, the 4-NO2 group is reduced to the amino group. Treatment with Fremy's salt produces the indoquinone structure. The 3-formyl group is reduced and converted to 4-NO2-phenyl carbonate compound A. Morphine is converted to the carbamate compound B through an activated carbonate intermediate. Compounds A and B are combined in the presence of an amine in DMF to provide the completed drug-linker unit after an acid catalyzed t-butyl ester hydrolysis (Scheme 9).

Provenance & Evidence