Crystalline Salt Forms of Compound I for Stable Purification

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Solution Overview

Problem

Existing methods for isolating and purifying the pharmaceutical compound 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (Compound (I)) lack reproducibility, physical and chemical stability, and sufficient solubility, especially under varying storage conditions, and are susceptible to pH effects.

Innovation Solution

Development of crystalline forms C and D of Compound (I), characterized by specific X-ray diffraction patterns, thermal properties, and NMR spectra, which provide stability and solubility, allowing for effective isolation and purification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional isolation and purification methods are used for Compound (I), then the compound can be obtained as a solid, but the method lacks reproducibility and the solid form exhibits poor physical and chemical stability under varying storage conditions

Engineering Contradiction:

Improvereproducibility of isolation and purificationVSAvoidphysical and chemical stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by developing specific crystalline forms (Form C and Form D) with defined structural parameters. These crystalline forms exhibit reproducible isolation and purification characteristics while maintaining superior physical and chemical stability across varying storage conditions, directly resolving the technical contradiction between reliability and stability.

Inventive Principle:

Principle #35Parameter changes

2Ease of manufacture

If conventional solid forms of Compound (I) are used, then isolation and purification can be performed, but the solubility in solvents/solutions is insufficient for preparation of other solid forms

Engineering Contradiction:

Improveisolation and purification processVSAvoidsolubility

Core Design Contradiction:

Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent resolves this contradiction by developing crystalline forms with optimized solubility parameters. Form C and Form D provide sufficient solubility in various solvents while maintaining ease of manufacture through reproducible isolation and purification processes, enabling preparation of other solid forms as needed.

Inventive Principle:

Principle #35Parameter changes

3Ease of manufacture

If existing salt forms of Compound (I) are used, then the compound can be isolated, but the forms are susceptible to pH effects and lack physical and chemical stability

Engineering Contradiction:

Improveisolation capabilityVSAvoidresistance to pH effects

Core Design Contradiction:

Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent addresses this contradiction by developing crystalline forms with enhanced pH resistance parameters. Form C and Form D maintain isolation capability while demonstrating superior resistance to pH effects and improved physical and chemical stability compared to existing salt forms.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12570637B2Crystalline salt forms 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-n-(methyld3) pyridazine-3-carboxamide

Publication Date: 2026.03.10 BRISTOL MYERS SQUIBB CO

AI summary

Disclosed are crystalline salt Forms C and D of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide. Form C is a MSA salt and Form D is a sulfate salt of Compound (I). Characterization data for the Forms are disclosed.