Total Synthesis of Rucaparib

Area of Science:

• Organic Synthesis
• Medicinal Chemistry
• Drug Development

Background:

• Rucaparib is an FDA-approved drug for treating ovarian and prostate cancers.
• Efficient and scalable synthetic routes are crucial for pharmaceutical production.

Purpose of the Study:

• To report a concise and efficient total synthesis of rucaparib.
• To utilize commercially available starting materials and minimize separation steps.

Main Methods:

• Heck reaction to form an (E)-2-aminocinnamonitrile derivative.
• Imino-Stetter reaction to construct the indole-3-acetonitrile core.
• Nitrile reduction followed by lactamization to yield the azepinone scaffold.

Main Results:

• The synthesis successfully produced rucaparib.
• The route involved only three separation operations.
• An overall yield of 54% was achieved.
• Commercially available starting materials were used.

Conclusions:

• A concise and efficient synthesis of rucaparib has been established.
• This method is suitable for large-scale production due to its efficiency and use of available materials.