Finerenone Intermediate Salt Route for High Optical Purity
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Solution Overview
Problem
Existing methods for preparing finerenone face challenges in achieving a consistently excellent yield and optical purity while minimizing costs and process complexity in mass production.
Innovation Solution
A method involving the preparation of intermediate compounds 2a and 3 through reactions with di-p-toluoyl-D-tartaric acid or (-)-camphor-10-sulfonic acid, followed by amide coupling using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, 4-dimethylaminopyridine, and ammonium hydroxide, allows for high yield and optical purity of finerenone without separate desalting processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If existing methods are used to prepare finerenone, then production can be achieved, but yield and optical purity are inconsistent and process complexity increases
Solution Approach 1:
The patent introduces di-p-toluoyl-D-tartaric acid as an intermediary resolving agent that mediates the separation of enantiomers during salt formation. This intermediary compound enables consistent optical purification without requiring complex multi-step resolution processes, thereby improving optical purity while simplifying the overall process complexity
Solution Approach 2:
The patent optimizes reaction parameters including temperature (15-90°C), solvent selection (acetonitrile, ethanol, methanol, THF), and equivalent ratios (1:0.5 to 1:3) to achieve consistent high optical purity and yield. By systematically controlling these parameters, the process achieves manufacturing precision without excessive complexity
2Productivity
If existing methods are used to prepare finerenone, then production can be achieved, but costs increase and process time increases
Solution Approach 1:
The patent combines salt formation and optical resolution into a single integrated step by reacting the racemic mixture directly with di-p-toluoyl-D-tartaric acid to form diastereomeric salts. This merging of operations eliminates separate resolution steps, reducing process time while maintaining high yield and productivity
Solution Approach 2:
The patent performs preliminary optimization of reaction conditions including temperature control (15-90°C), solvent selection, and equivalent ratios before scale-up. This preliminary action ensures consistent high yield from the outset and reduces the need for iterative process adjustments, thereby reducing overall process time
3Stability of the object's composition
If existing methods are used to prepare finerenone, then production can be achieved, but stability of intermediate compounds decreases
Solution Approach 1:
The patent employs di-p-toluoyl-D-tartaric acid, a chiral compound with specific asymmetric structure, to form diastereomeric salts with the racemic mixture. This asymmetry creates stable, separable crystalline forms with distinct physical properties, improving the stability of intermediate compounds while maintaining ease of manufacture through straightforward filtration and washing procedures
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 method enables the production of finerenone with high yield and optical purity, reducing costs and process complexity by utilizing stable intermediate compounds 2a and 3, which can be easily obtained as solids and reused, thereby improving productivity.
Implementation Method 1
a step of preparing compound 2a represented by formula 2a or compound 3 represented by formula 3 by using compound 1 represented by formula 1; wherein compound 2a or 3 is a salt of compound 1a
Implementation Method 2
each of compounds 2a and 3 can be a stable material, and can be easily obtained as a solid without a separate purification process
Data Source
AI summary
The present invention relates to a method for preparing finerenone, an intermediate compound of finerenone, and a method for preparing the same. Finerenone is prepared by using an intermediate compound represented by formula 2a or an intermediate compound represented by formula 3. AA Chemical formula 2a BB Chemical formula 3