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In the present work, a new synthetic method toward a key intermediate in the total synthesis of alkannin and shikonin is developed. The key intermediate, 4-methyl-1-(naphtho[1,8- de :4,5- d'e' ]bis([1,3]dioxine)-4-yl)pent-3-en-1-one (5), is synthesized via the reaction of 1,8:4,5-bis(methylenedioxy)naphthalene-2-carboxylic acid N -methoxy- N -methylamide with prenyllithium. This synthetic approach avoids the use of N -methoxy- N,4-dimethylpent-3-enamide, which is not easy to obtain, and the toxic reagent sodium cyanide. [ABSTRACT FROM AUTHOR]

A novel synthetic route toward vilazodone is described by using 4-cyanoaniline and 5-bromo-2-hydroxybenzaldehyde as starting materials, with an overall yield of 24% and 99% purity. First, the intermediate (3-(4-chlorobutyl)-1 H -indole-5-carbonitrile) is synthesized via diazotization of 4-cyanoaniline, followed by Fischer indole cyclization with 6-chlorohexanal. Subsequently, another intermediate, 5-(piperazin-1-yl)benzofuran-2-carboxamide, is generated via aromatic nucleophilic substitution of 5-bromobenzofuran-2-carboxamide with piperazine. Finally, vilazodone is obtained via nucleophilic substitution of the above two key intermediates by treatment with Et3N/K2CO3. In comparison to the original process, this route avoids the use of expensive and toxic reagents and resolves issues such as safety, environmental concerns, and high costs. [ABSTRACT FROM AUTHOR]