Eluxadoline Synthesis via Segmented Deprotection and Reductive Amination
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Solution Overview
Problem
Current processes for preparing eluxadoline are not environmentally friendly, cost-effective, or industrially advantageous, and there is a need for improved methods to achieve high chromatographic purity.
Innovation Solution
The development of a process involving deprotection and reductive amination steps, followed by acid treatment, to produce eluxadoline and its intermediates with high chromatographic purity, using environmentally friendly conditions and cost-effective methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional processes are used for preparing eluxadoline, then the process is simpler and more established, but the chromatographic purity is insufficient and environmental friendliness is compromised
Solution Approach 1:
The synthesis process is divided into distinct modular stages: deprotection of the nitrogen protecting group, reductive amination with the appropriate aldehyde or ketone, and acid treatment to form the final salt. Each stage can be independently optimized and controlled to ensure high purity at each step, contributing to the overall 97% chromatographic purity of eluxadoline.
Solution Approach 2:
The nitrogen protecting group is removed in advance before the reductive amination step, preparing the amine in its free form for subsequent coupling. This preliminary deprotection action ensures that the amine is ready for optimal reaction conditions in the next step, preventing side reactions and improving overall purity.
2Object-affected harmful factors
If conventional processes are used for preparing eluxadoline, then the process is more established, but environmental friendliness and cost-effectiveness are compromised
Solution Approach 1:
The process employs environmentally benign solvents and reagents, modifies reaction conditions to reduce waste, and optimizes stoichiometry to minimize byproducts. These parameter changes make the process more environmentally friendly while maintaining industrial feasibility through straightforward deprotection, reductive amination, and acid treatment steps.
3Ease of manufacture
If current processes are used for preparing eluxadoline, then the process is simpler, but cost-effectiveness and industrial advantage are compromised
Solution Approach 1:
The process selectively removes the nitrogen protecting group through deprotection, isolating the free amine for subsequent reductive amination. This extraction of the protecting group allows for precise control over the reaction sequence and ensures high purity of the final product by eliminating protecting group residues.
Solution Approach 2:
The patent utilizes intermediate compounds (such as the deprotected amine and reductive amination products) that serve as well-defined intermediates with characterized structures. These intermediates facilitate controlled progression through the synthesis route, enabling quality control at each stage and ensuring the final 97% chromatographic purity while maintaining cost-effectiveness.
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
The process achieves chromatographic purities of about 97% for eluxadoline and its intermediates, providing an industrially advantageous and environmentally friendly solution.
Implementation Method 1
deprotecting a compound of Formula II wherein PG is a nitrogen protecting group, in the presence of a deprotecting agent to obtain a compound of Formula III
Implementation Method 2
reductive amination of the compound of Formula III with a compound of Formula IV followed by the treatment with an acid to obtain a compound of Formula V
Data Source
AI summary
The present invention relates to processes for the preparation of eluxadoline. The present invention also provides a compound of Formula V, a process for its preparation, and its use for the preparation of eluxadoline.