One-Pot Dimeric MRI Contrast Agent Synthesis
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Solution Overview
Problem
The existing process for preparing dimeric contrast agents for MRI is inefficient and unsuitable for large-scale production due to the need for harsh materials and intermediates that cause corrosion and safety concerns, leading to reduced yield and efficiency.
Innovation Solution
A one-pot process that eliminates the isolation of intermediates and avoids the use of harsh reagents like TFA and DCM, using aqueous solvents to improve yield and safety, resulting in a more efficient and scalable method for producing the dimeric complex compound 5.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the prior art process is used to prepare dimeric contrast agents, then the synthesis can be carried out, but the overall yield is reduced and the process is unsuitable for large-scale production due to multiple isolation steps and harsh materials
Solution Approach 1:
The patent combines multiple separate synthesis steps into a single one-pot process. Instead of isolating intermediates after each step (alkylation, deprotection, complexation), all transformations are performed in one reaction vessel, eliminating multiple isolation steps and significantly improving overall yield while simplifying the process for large-scale production
Solution Approach 2:
The patent maintains continuous reaction conditions throughout the synthesis process without interrupting for isolation and purification. The reaction mixture progresses directly from alkylation through deprotection to complexation without breaking the reaction flow, thereby reducing material loss and improving productivity
2Ease of manufacture
If harsh materials like TFA, TIPS and DCM are used in the synthesis process, then the reactions can proceed, but corrosion and safety issues arise making the process unsuitable for industrial scale
Solution Approach 1:
The patent changes the chemical parameters of the reaction system by replacing harsh reagents (TFA, TIPS, DCM) with milder aqueous conditions. This parameter change maintains reaction reactivity while eliminating corrosion and safety hazards associated with harsh materials, making the process suitable for industrial implementation
Solution Approach 2:
The patent employs benign, easily disposed-of aqueous reagents instead of expensive, hazardous reagents. The aqueous system uses water and mild acids/bases that are safe, inexpensive, and environmentally friendly, replacing costly and hazardous materials like TFA and DCM with safer alternatives
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 significantly increases the overall yield from 10% to at least 20%, preferably 25-30%, and is safer for industrial-scale implementation by reducing the use of hazardous materials and simplifying the production steps.
Implementation Method 1
using aqueous solvents to improve yield and safety
Implementation Method 2
removing the tert-butyl protecting groups from the protected ligand to obtain a solution of a respective free ligand
Implementation Method 3
adding gadolinium metal ions to the solution of step 4) to obtain a solution of the respective dimeric complex of formula 5
Data Source
AI summary
The invention relates to a process for the preparation of dimeric contrast agents for use in Magnetic resonance Imaging (MRI), in particular [μ-[1-[bis[2-(hydroxy-kO)-3- [4,7,10-tris[(carboxy-kO)methyl]-1,4,7,10-tetraazacyclododec-1-yl- kN1,kN4,kN7,kN10]propyl]amino]-1-deoxy-D-glucitolato(6-)]]di-gadolinium complex, which includes preparation steps carried out one-pot and without isolation of the obtained intermediate.