Isavuconazonium Salt Preparation Without Chromatography or Lyophilization
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Solution Overview
Problem
Existing processes for producing Isavuconazonium sulfate require chromatographic purification, ion exchange chromatography, and lyophilisation, making them unsuitable for large-scale production, and result in low purity and yield.
Innovation Solution
A process involving the reaction of compound (2) with first and second acids in a water-immiscible solvent, followed by transformation with a third acid, eliminating the need for chromatographic purification and lyophilisation, and allowing isolation of high-purity salts through solvent distillation and precipitation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If chromatographic purification and ion exchange chromatography are used, then purity of Isavuconazonium sulfate is improved, but device complexity and production cost increase making it unsuitable for large-scale production
Solution Approach 1:
The invention extracts and eliminates the need for complex chromatographic purification and ion exchange steps by using a simplified acid-base reaction sequence in water-immiscible solvents, achieving high purity through selective precipitation and filtration instead
Solution Approach 2:
The invention replaces expensive, complex chromatographic systems with simple, inexpensive acid-base reactions and filtration steps, using readily available reagents and equipment suitable for large-scale production
2Manufacturing precision
If lyophilisation is used for salt isolation, then purity is improved, but energy consumption increases making it unsuitable for high scale production
Solution Approach 1:
The invention uses controlled phase transitions of the salt between soluble and insoluble states through pH adjustment and solvent selection, enabling isolation by precipitation and filtration instead of energy-intensive lyophilisation
Solution Approach 2:
The invention changes physical-chemical parameters (pH, solvent type, temperature) to control salt solubility and enable isolation through simple filtration, replacing the need for lyophilisation while maintaining high purity
3Manufacturing precision
If existing purification processes are used, then sufficient purity is achieved, but productivity decreases due to multiple complex steps
Solution Approach 1:
The invention segments the synthesis into distinct acid-base reaction steps with intermediate isolation, allowing each step to be optimized independently and enabling continuous processing for higher productivity while maintaining purity
Solution Approach 2:
The invention performs preliminary protection group installation and selective deprotection steps that pre-position functional groups for efficient final salt formation, reducing the number of purification steps needed and improving overall productivity
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 high-purity Isavuconazonium sulfate with improved yield, suitable for large-scale production, without the need for costly and energy-intensive techniques like chromatography and lyophilisation.
Implementation Method 1
Reacting compound of formula (2) with a first acid HA1 to obtain compound (3)
Implementation Method 2
Reacting compound of formula (3) with a second acid HA2 in a water immiscible solvent to obtain a mixture comprising compound (4) in the water immiscible solvent
Implementation Method 3
They can be isolated without using lyphilization technique by simple distilling off the solvent
Implementation Method 4
transformation of a to salts of compound of formula (1) with an acid HA2 of formula CX3(CX2)mCOOH, m is between 0 and 7 and X is selected from H or Cl or F to a different salt insoluble in a water immiscible solvent
Implementation Method 5
They can be also transformed into a different salt of compound of formula (1), for example the salts disclosed in the prior art that are insoluble in a water immiscible solvent and can be isolated by precipitation without a need of lyophilization
Data Source
AI summary
The present invention relates to the process of preparation of salts of compound of formula (1).