Opioid Modulator Synthesis via Palladium Catalysis
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Solution Overview
Problem
Existing methods for preparing opioid modulators, such as compounds of formula (I) and (II), require expensive dimethyl-tyrosine, making large-scale synthesis impractical.
Innovation Solution
A process involving reacting a compound of formula (X) with a suitably substituted compound of formula (XVIII) in the presence of a palladium catalyst and an organic or inorganic base, followed by hydrogenation and reaction with an aqueous base, to yield compounds of formula (I), which are useful as opioid receptor modulators.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If dimethyl-tyrosine is used in the preparation of opioid modulators, then the compounds can be synthesized, but the cost increases significantly making large-scale production impractical
Solution Approach 1:
The patent replaces expensive dimethyl-tyrosine with cheaper alternative starting materials such as commercially available amino acids and building blocks. The synthesis route uses inexpensive reagents and catalysts, enabling cost-effective large-scale production while maintaining the desired pharmaceutical activity of the opioid modulators.
Solution Approach 2:
The patent modifies the synthesis parameters and route by changing the starting materials, reaction conditions, and processing parameters. This allows the production to be scaled up to large quantities while controlling costs through optimized material selection and process parameters.
2Productivity
If existing synthesis methods are used, then opioid modulators can be prepared, but the process is not suitable for large scale production due to high material costs
Solution Approach 1:
The patent divides the synthesis process into discrete, manageable steps using modular building blocks that can be independently optimized. This segmentation allows each step to be scaled and optimized separately, improving overall productivity and manufacturing feasibility for large-scale production.
Solution Approach 2:
The patent introduces intermediate compounds and catalysts that facilitate the transformation from inexpensive starting materials to the target opioid modulators. These intermediaries enable efficient coupling reactions and improve the overall yield and scalability of the synthesis process.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This process allows for the cost-effective preparation of opioid receptor modulators suitable for large-scale production, addressing the expense issue with dimethyl-tyrosine and enabling their use in treating pain and gastrointestinal disorders.
Implementation Method 1
reacting the compound of formula (XII) with a suitably substituted compound of formula (XVIII); in the presence of palladium catalyst
Implementation Method 2
reacting the compound of formula (XIX) with hydrogen or a source of hydrogen; in the presence of a catalyst
Implementation Method 3
reacting the compound of formula (XX) with an aqueous base; in an organic solvent; to yield the corresponding compound of formula (I)
Data Source
AI summary
The present invention is directed to novel processes for the preparation of opioid modulators (agonists and antagonists) and intermediates in their synthesis. The opioid modulators are useful for the treatment and prevention of as pain and gastrointestinal disorders.