Ozanimod Synthesis Without Chromatographic Purification
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing processes for preparing ozanimod are tedious and expensive due to chromatographic purification steps, and there is a need for a scalable, industrial-scale process that maintains purity and yield without chromatographic purification.
Innovation Solution
A process involving reacting compound (7) with (R)3SiOM in a solvent, followed by addition of an acid or silicagel, and isolating ozanimod from alkyl acetate or alcohol, optionally salifying the compound to achieve high purity and yield.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If chromatographic purification steps are used to prepare ozanimod, then product purity is improved, but process complexity and cost increase significantly
Solution Approach 1:
The invention extracts and eliminates the chromatographic purification steps from the synthesis process. By using a multi-step chemical synthesis approach with intermediate purification steps (filtration, extraction), the process achieves the desired product purity without requiring complex chromatographic equipment or procedures, thus resolving the contradiction between purity and process complexity
Solution Approach 2:
The synthesis process is divided into multiple discrete steps (Step 1: formation of intermediate I, Step 2: formation of intermediate II, Step 3: formation of ozanimod), each with its own purification method. This segmentation allows for simpler, more manageable purification steps at each stage rather than requiring a single complex chromatographic step, reducing overall process complexity while maintaining product purity
2Manufacturing precision
If chromatographic purification steps are used to prepare ozanimod, then product purity is improved, but production cost increases
Solution Approach 1:
The invention replaces expensive chromatographic purification materials (columns, resins, solvents) with cheaper, disposable-like simple filtration and extraction steps using common laboratory equipment and inexpensive reagents. This dramatically reduces production cost while achieving the required product purity through multiple simpler steps
Solution Approach 2:
The invention changes the purification parameters from chromatographic conditions (stationary phase, mobile phase gradients, flow rates) to simple filtration and extraction parameters (solvent choice, temperature, pH adjustment). This parameter change enables the use of less expensive methods while maintaining effective purification
3Manufacturing precision
If chromatographic purification steps are used to prepare ozanimod, then product purity is improved, but processing time increases
Solution Approach 1:
The invention skips the time-consuming chromatographic purification steps entirely and rushes through the synthesis process using faster alternative methods. The multi-step synthesis with simple filtration and extraction steps completes much faster than chromatographic purification, improving productivity while maintaining product purity through systematic intermediate purification
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 ozanimod with good purity and yield without chromatographic purification, suitable for industrial scale, using alkyl acetate or alcohol for isolation and potentially forming a salt with acids like hydrochloric acid.
Implementation Method 1
Reacting compound (7) in a presence of a compound of formula (R)3SiOM, where R is selected from C1-C5 alkyl or aryl and M is selected from Na, K or Li, in a solvent to provide compound (1)
Implementation Method 2
Addition of an acid or silicagel
Implementation Method 3
Isolation of compound (I) from alkyl acetate or an alcohol or a mixture thereof
Data Source
AI summary
The present invention relates to the process of preparation of compound of formula (I) or a salt thereof. Further it relates to the solid form of compound (I).