A cyanide-catalyzed imino-Stetter reaction enables the concise total syntheses of rucaparib was written by Park, Jinjae;Cheon, Cheol-Hong. And the article was included in RSC Advances in 2022.Synthetic Route of C9H7BrFNO4 This article mentions the following:
Two routes toward the synthesis of rucaparib, an FDA-approved drug used for the treatment of ovarian and prostate cancers, have been developed from com. available starting materials utilizing the cyanide-catalyzed imino-Stetter reaction as the key step for the construction of the indole motif bearing all the desired substituents in their correct positions. In the first-generation synthesis, meta-fluorobenzoate, the starting material currently used in the process chem. route of rucaparib, was converted into 4,6-disubstituted 2-aminocinnamic acid derivatives (ester or amide). The cyanide-catalyzed imino-Stetter reaction of aldimines derived from the resulting 2-aminocinnamic acid derivatives and a com. available aldehyde afforded the desired indole-3-acetic acid derivatives The final azepinone formation completed the total synthesis of rucaparib in 27% overall yield. To resolve the issues raised in the first-generation synthesis, we further developed a second-generation synthesis of rucaparib. The Heck reaction of a com. available ortho-iodoaniline derivative with acrylonitrile provided 4,6-disubstituted 2-aminocinnamonitrile, which was subjected to the imino-Stetter reaction with the same aldehyde to provide the desired indole-3-acetonitrile product. Subsequent construction of the azepinone scaffold completed the total synthesis of rucaparib in 59% overall yield over three separation operations. The synthetic strategy reported herein can provide a highly practical route to access rucaparib from com. available starting materials (5.2% overall yield in the current process chem. route vs. 59% overall yield in the second-generation synthesis). In the experiment, the researchers used many compounds, for example, Methyl 2-(bromomethyl)-5-fluoro-3-nitrobenzoate (cas: 850462-65-6Synthetic Route of C9H7BrFNO4).
Methyl 2-(bromomethyl)-5-fluoro-3-nitrobenzoate (cas: 850462-65-6) belongs to organobromine compounds. Most of the natural organobromine compounds are produced by marine organisms, and several brominated metabolites with antibacterial, antitumor, antiviral, and antifungal activity have been isolated from seaweed, sponges, corals, molluscs, and others. When the molecular ion is detected, the bromine and chlorine isotope patterns are very distinct, but caution is to be exercised for certain mixed chlorinated/brominated compounds, which can look similar to homohalogen patterns.Synthetic Route of C9H7BrFNO4
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary