Polymorph Form A Stabilization for Nematocidal Sulfonamide
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Solution Overview
Problem
The challenge lies in predicting and stabilizing the solid forms of chemical compounds like 8-chloro-N-[(2-chloro-5-methoxyphenyl)sulfonyl]-6-(trifluoromethyl)-imidazo[1,2-a]pyridine-2-carboxamide, as existing methods fail to accurately predict their crystal forms and physiochemical properties, affecting their biological efficacy and stability.
Innovation Solution
A specific polymorph, Form A, of the compound is characterized by a unique powder X-ray diffraction pattern and prepared through a method involving a reaction mixture of 2-chloro-5-methoxybenzene sulfonamide and 8-chloro-6-trifluoromethyl-imidazo[1,2-a]pyridine-2-carbonyl chloride in the presence of specific solvents, converting intermediate solid forms into polymorph Form A using toluene, ethyl acetate, water, methanol, acetone, or n-heptane.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional solid form prediction methods are used for chemical compounds, then the general process can be completed, but the prediction of crystal forms and physiochemical properties remains inaccurate and impossible
Solution Approach 1:
The patent applies parameter changes by systematically varying crystallization conditions including solvent types (water, alcohols, esters, ethers, ketones, nitriles, carboxylic acids), temperature ranges, pH levels, and concentrations to transform the compound into different polymorphic forms. This enables accurate prediction and control of crystal forms and their physiochemical properties through controlled parameter modification rather than relying on inaccurate conventional prediction methods
Solution Approach 2:
The patent utilizes phase transitions by inducing controlled crystallization from solution phases to solid crystalline phases. Through systematic variation of crystallization parameters, the compound transitions between different polymorphic crystal forms, each with distinct and accurately predictable physiochemical properties such as solubility, dissolution rate, and stability
2Adaptability or versatility
If multiple solid forms of a compound are discovered, then more formulation options become available, but the complexity of stabilizing and characterizing each form increases
Solution Approach 1:
The patent applies preliminary action by establishing comprehensive stabilization protocols before formulation development. Each polymorphic form is pre-characterized and stabilized through controlled crystallization procedures, defining specific storage conditions and handling protocols in advance. This preliminary stabilization ensures reliable form selection and maintains formulation versatility without compromising stability
Solution Approach 2:
The patent uses intermediary approaches by employing solvent molecules as mediators during crystallization to guide the formation of specific polymorphic forms. These solvent intermediaries facilitate controlled nucleation and crystal growth, enabling reliable production of desired solid forms while maintaining formulation flexibility
3Productivity
If accurate prediction of melting point and solubility is achieved, then drug development efficiency improves, but the ability to predict these properties for new crystal forms remains impossible
Solution Approach 1:
The patent applies preliminary action by performing comprehensive physiochemical characterization including melting point and solubility measurements during the initial polymorph screening phase. This preliminary data collection enables efficient drug development by providing accurate physiochemical properties early in the process, eliminating the need for later predictive attempts on new crystal forms
Solution Approach 2:
The patent uses parameter changes to systematically explore and characterize different crystal forms with varying physiochemical properties. By controlling crystallization parameters and measuring resulting properties, the method establishes accurate empirical data for melting point, solubility, and other critical parameters, enabling informed drug development decisions
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 approach stabilizes the polymorph Form A, enhancing its chemical and physical stability, improving biological performance and nematocidal efficacy, and facilitating the development of effective formulations for nematode control.
Implementation Method 1
characterized by a powder X-ray diffraction pattern having at least the 2θ reflection positions 30.367, 29.131, 27.995, 27.611, 26.49, 25.973, 25.604, 24.285, 23.582 and 19.789 degrees
Implementation Method 2
mixing the solid form of Compound 1 with a second solvent to convert the solid form to the polymorph Form A
Implementation Method 3
forming a reaction mixture by contacting 2-chloro-5-methoxybenzene sulfonamide and 8-chloro-6-trifluoromethyl-imidazo[1,2-a]pyridine-2-carbonyl chloride in the presence of a first solvent to form a solid form of Compound 1
Data Source
Figure 1A~1D
AI summary
Disclosed are solid forms of 8-chloro-N-[(2-chloro-5-methoxyphenyl)sulfonyl]-6-(trifluoromethyl)-imidazo[1,2-alpha]pyridine-2-carboxamide (Compound 1). Methods for the preparation of solid forms of Compound 1 and for the conversion of one solid form of Compound 1 into another are disclosed. Disclosed are nematocidal compositions comprising a nematocidally effective amount of a solid form of Compound 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid carriers. Compositions comprising a mixture of a solid form of Compound 1 and at least one other nematicide, insecticide and/or fungicide are also disclosed. Also disclosed are methods for protecting a plant from nematodes comprising applying to the plant, or portion, or seed thereof, or to the growing medium of the plant, a nematocidally effective amount of Compound 1 comprising the polymorph Form A.