4,5-Dihydro-pyrazolo[3,4-c]pyrid-2-one Synthesis via Segmented Steps
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Solution Overview
Problem
Current methods for the large-scale synthesis of 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones, which are potential factor Xa inhibitors, lack practical and efficient processes for producing these compounds and their intermediates.
Innovation Solution
A novel process involving the reaction of compounds of formula I with formula II in the presence of a base, followed by specific transformations such as reduction, cyclization, and amidation, using various solvents and catalysts to produce 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional methods are used for synthesis, then the process is simple, but the productivity and manufacturing efficiency are insufficient for large-scale production
Solution Approach 1:
The synthesis process is divided into multiple discrete steps: (1) formation of hydrazonyl compound, (2) cycloaddition to form pyrazolo-pyridinone core, (3) reduction of nitro group, (4) amidation to form lactam, and (5) cyclization to form final product. Each step can be optimized independently for scalability
Solution Approach 2:
The patent employs preliminary actions by forming protected intermediates (hydrazonyl compounds with specific substituents) before performing the main cycloaddition reaction. This allows optimization of reaction conditions and improves overall yield for large-scale production
2Manufacturing precision
If existing synthesis methods are used, then the procedure is straightforward, but the manufacturing precision and purity are insufficient for clinical applications
Solution Approach 1:
The patent extracts and removes harmful byproducts through specific purification steps at each stage. For example, the reduction step uses selective conditions to remove the nitro group without affecting other sensitive groups, and subsequent purification steps remove impurities to achieve high purity for clinical applications
Solution Approach 2:
The patent utilizes parameter changes in reaction conditions (temperature, pH, solvent selection, catalyst concentration) to optimize both purity and ease of manufacture. For instance, the cycloaddition reaction uses controlled temperature and base concentration to achieve high purity pyrazolo-pyridinone core formation
3Loss of substance
If traditional synthesis approaches are used, then the process is simple, but the loss of substance and material efficiency are high
Solution Approach 1:
The patent implements waste minimization by recovering and reusing reagents and solvents across multiple steps. For example, bases used in deprotonation steps can be recovered and reused, and solvents are recycled between extraction and purification steps, significantly reducing material loss for large-scale production
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
This process enables the efficient production of 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones on a multigram or industrial scale, facilitating their use in clinical settings and drug development.
Implementation Method 1
contacting a compound of formula I with a compound of formula II in the presence of a base
Implementation Method 2
reducing the B group of formula III to an amino group
Implementation Method 3
cyclizing the compound of formula IV to form a compound of formula V
Implementation Method 4
contacting the resulting amino compound with an alkyl-acid halide to form a compound of formula IV
Data Source
AI summary
A novel process and intermediates thereof for making 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones of the type shown below from appropriate phenyl hydrazines is described.These compounds can be useful as factor Xa inhibitors.