Imidazopyridazine Synthesis Yield via Base-Phosphorus Control
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for producing imidazo[1,2-b]pyridazine compounds, such as 2,6-dichloroimidazo[1,2-b]pyridazine, are inefficient and result in low yields, particularly when using the known process involving 3-imino-6-chloro-2,3-dihydropyridazine-2-acetic acid and phosphorus oxychloride.
Innovation Solution
A process involving the reaction of a 2,3-dihydropyridazine compound with phosphorus oxyhalide in the presence of an organic base, where the organic base is used in amounts of 0.5 mole or more relative to the 2,3-dihydropyridazine compound and 1 mole or less relative to the phosphorus oxyhalide, at temperatures between 60 to 180°C, to produce imidazo[1,2-b]pyridazine compounds efficiently.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the known process using 3-imino-6-chloro-2,3-dihydropyridazine-2-acetic acid and phosphorus oxychloride is used, then the production method is simple, but the yield is low
Solution Approach 1:
The invention changes the parameters of the reaction system by introducing a specific organic base (0.5-1.0 equivalent relative to the 2,3-dihydropyridazine compound) and adjusting the reaction temperature range (60-180°C). These parameter modifications optimize the reaction conditions to significantly improve yield while maintaining reasonable process complexity.
Solution Approach 2:
The invention introduces an organic base as an intermediary substance that facilitates the reaction between the 2,3-dihydropyridazine compound and phosphorus oxyhalide. This intermediary plays a crucial role in improving the reaction efficiency and yield without requiring complex multi-step procedures.
2Productivity
If the known process is used, then the production method is simple, but the production efficiency is low
Solution Approach 1:
By optimizing reaction parameters including the addition of organic base (0.5-1.0 equivalent) and controlling temperature (60-180°C), the invention significantly enhances production efficiency. The modified parameters enable better reaction control and higher yield while keeping the manufacturing process relatively simple and direct.
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 significantly improves the yield of imidazo[1,2-b]pyridazine compounds, achieving yields of up to 96% as demonstrated in the examples, making the production more efficient and effective compared to existing methods.
Implementation Method 1
reacting a 2,3-dihydropyridazine compound represented by the formula (1) with a phosphorus oxyhalide in the presence of an organic base
Implementation Method 2
at temperatures between 60 to 180°C
Data Source
AI summary
A process for producing an imidazo[1,2-b]pyridazine compound represented by the formula (2):wherein R1, R2 and R3 are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group which may be substituted with a halogen atom or atoms, an alkenyl group which may be substituted with a halogen atom or atoms, or an alkoxy group which may be substituted with a halogen atom or atoms, which comprises reacting a 2,3-dihydropyridazine compound represented by the formula (1):wherein R1, R2 and R3 are the same meanings as defined above, with a phosphorus oxyhalide in the presence of an organic base which is in an amount of 0.5 mole or more relative to 1 mole of the 2,3-dihydropyridazine compound and 1 mole or less relative to 1 mole of the phosphorus oxyhalide.