Niraparib Synthesis via Low-Temperature Reaction
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current processes for synthesizing Niraparib face challenges such as the use of hazardous chemicals, low yields, and the formation of impurities, making them unsuitable for large-scale industrial production.
Innovation Solution
A new process involving the reaction of compound (III) with compound (IV) to obtain compound (II), followed by conversion to Niraparib or its salt, which avoids the use of hazardous pyridine and reduces impurity formation, particularly by performing the reaction at lower temperatures and avoiding carbon-nitrogen cross-coupling, thereby increasing yield and purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If conventional processes are used for synthesizing Niraparib, then the synthesis can be completed, but hazardous chemicals like pyridine must be used and impurities are formed
Solution Approach 1:
The patent changes the reaction parameters by performing the reaction at lower temperatures (0-25°C) compared to conventional high-temperature processes. This parameter change eliminates the need for hazardous chemicals like pyridine while maintaining high yields, directly resolving the contradiction between safety and productivity
Solution Approach 2:
The patent extracts and removes the harmful pyridine solvent from the reaction system by using alternative solvents or solvent-free conditions. This extraction of the harmful component allows the synthesis to proceed without hazardous chemicals while preserving the reaction efficiency through optimized alternative conditions
2Productivity
If conventional processes are used for synthesizing Niraparib, then the synthesis can be completed, but low yields are obtained
Solution Approach 1:
The patent changes multiple reaction parameters including temperature (lower temperatures), solvent types, and reaction time to optimize the synthesis. These parameter changes simultaneously increase the yield by improving reaction efficiency and reduce impurities by preventing side reactions, resolving the contradiction between productivity and purity
3Productivity
If conventional processes are used for synthesizing Niraparib, then the synthesis can be completed, but the process is not suitable for large-scale industrial production
Solution Approach 1:
The patent modifies reaction parameters to be more suitable for industrial scale-up, including lower temperatures that are easier to control in large reactors, elimination of hazardous pyridine that simplifies safety protocols and waste handling, and optimized reaction conditions that improve overall process efficiency and scalability
Solution Approach 2:
The patent converts the potential harm of requiring complex purification to remove pyridine and its byproducts into a benefit by using alternative reaction conditions that inherently produce fewer impurities. This approach simplifies the industrial process by eliminating the need for complex purification steps while maintaining high product quality
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 higher yields and purity of Niraparib with reduced impurities, making it more cost-effective and suitable for industrial production.
Implementation Method 1
the step of reacting compound of formula (III) with compound of formula (IV) to obtain compound of formula (II)
Implementation Method 2
performing the reaction at lower temperatures
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to novel procedures and novel intermediates useful in the synthesis of Niraparib or any salt thereof.