5-[[1-(3-Fluoropropyl)azetidin-3-yl]amino]pyridine-2-carbaldehyde
[CAS# 2407535-11-7]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound
• Name: 5-[[1-(3-Fluoropropyl)azetidin-3-yl]amino]pyridine-2-carbaldehyde
• Molecular Formula: C₁₂H₁₆FN₃O
• Molecular Weight: 237.27
• CAS Registry Number: 2407535-11-7
• SMILES: C1C(CN1CCCF)NC2=CN=C(C=C2)C=O

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 387.6±42.0 ºC 760 mmHg (Calc.)^*
• Flash point: 188.2±27.9 ºC (Calc.)^*
• Index of refraction: 1.601 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P280-P305+P351+P338

Discovory and Applicatios

Arylamino derivatives of estrogen receptor modulators represent a class of compounds with significant therapeutic potential. These molecules are characterized by the presence of an arylamino group attached to a substituted phenyl or pyridinyl moiety, which allows selective interaction with estrogen receptors. Such modulators can influence receptor activity in a tissue-specific manner, providing advantages for the treatment of hormone-related conditions while minimizing side effects associated with systemic estrogen therapy.

The synthesis of these compounds involves advanced organic chemistry strategies, including the construction of fused tricyclic cores and the incorporation of substituents such as fluorinated azetidine moieties. One notable compound in this class is 5-[[1-(3-fluoropropyl)azetidin-3-yl]amino]pyridine-2-carbaldehyde, which serves as a key intermediate for the preparation of tricyclic estrogen receptor modulators. The introduction of fluorinated groups into the azetidine ring enhances metabolic stability and receptor binding affinity, providing desirable pharmacokinetic properties for therapeutic use.

Solid forms of these compounds have been optimized to improve their physicochemical properties. Patents describe the preparation of crystalline forms of tricyclic compounds containing substituted phenyl or pyridinyl moieties, including the fluorinated azetidine intermediates. Such solid forms facilitate reliable formulation and consistent bioavailability. Methods for producing these solids include crystallization and salt formation, which are essential for pharmaceutical development and large-scale production. Tartrate salts, in particular, have been reported to enhance solubility and stability, enabling more effective administration in clinical applications.

The compounds have applications in the treatment of various cancers and other estrogen-related disorders. By modulating estrogen receptor activity, these molecules can inhibit tumor growth in hormone-dependent cancers or selectively activate beneficial pathways in other tissues. The patents describe methods of using these compounds for therapeutic purposes, highlighting their potential as targeted treatments that leverage receptor selectivity to achieve clinical efficacy. The compounds’ chemical structures, including the fluorinated azetidine substituents, are crucial for their interaction with estrogen receptors and for the modulation of receptor-mediated signaling pathways.

Processes for synthesizing these intermediates and final compounds are well-documented in multiple patent filings. Methods include the preparation of substituted indole intermediates and fused tricyclic cores that incorporate the arylamino and fluorinated substituents. The synthetic routes are designed for efficiency, scalability, and reproducibility, which are necessary for industrial production. Several patents provide detailed protocols for preparing these compounds in solid form and for generating pharmaceutically acceptable salts, ensuring that the materials are suitable for therapeutic applications.

In addition to cancer therapy, these compounds have broader applications in research on estrogen receptor biology. They serve as chemical tools to probe receptor activity and to develop structure-activity relationships that inform the design of next-generation modulators. The combination of fluorinated azetidine intermediates and tricyclic scaffolds provides a versatile platform for the development of molecules with improved receptor selectivity and pharmacological profiles.

Overall, 5-[[1-(3-fluoropropyl)azetidin-3-yl]amino]pyridine-2-carbaldehyde and related arylamino derivatives constitute an important class of estrogen receptor modulators. Their optimized solid forms, detailed synthetic processes, and documented therapeutic applications demonstrate their significance in both pharmaceutical development and biomedical research. The ability to selectively modulate estrogen receptor activity provides opportunities for targeted treatment of hormone-dependent conditions with minimized systemic effects.

References

China Patent CN-117813288-A (2021) Arylamino derivative estrogen receptor modulators and their uses. Link


United States Patent US-2024208932-A1 (2021) Arylamino derivative estrogen receptor modulator and use thereof. Link

United States Patent US-10954234-B2 (2018) Solid forms of 3-((1R,3R)-1-(2,6-difluoro-4-((1-(3-fluoropropyl)azetidin-3-yl)amino)phenyl)-3-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)-2,2-difluoropropan-1-ol and processes for preparing fused tricyclic compounds comprising a substituted phenyl or pyridinyl moiety, including methods of their use. Link