1-(3-Fluoropropyl)azetidin-3-amine
[CAS# 1538772-53-0]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Amine
• Name: 1-(3-Fluoropropyl)azetidin-3-amine
• Molecular Formula: C₆H₁₃FN₂
• Molecular Weight: 132.18
• CAS Registry Number: 1538772-53-0
• SMILES: C1C(CN1CCCF)N

Properties

• Density: 1.0±0.1 g/cm³ Calc.^*
• Boiling point: 167.9±35.0 ºC 760 mmHg (Calc.)^*
• Flash point: 55.3±25.9 ºC (Calc.)^*
• Index of refraction: 1.456 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS02;GHS05;GHS07 Danger
• Hazard Statements: H302-H314-H226
• Precautionary Statements: P501-P270-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P303+P361+P353-P301+P330+P331-P363-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P403+P235-P405
• Transport Information: UN 2920

Discovory and Applicatios

1-(3-Fluoropropyl)azetidin-3-amine is a fluorinated azetidine derivative that has gained attention as a versatile intermediate in medicinal chemistry. Its chemical structure features a four-membered azetidine ring substituted with an amino group at the 3-position and a 3-fluoropropyl chain at the nitrogen atom. This combination of a constrained cyclic amine and a fluorinated alkyl side chain makes the molecule valuable for the design of bioactive compounds, particularly in the context of estrogen receptor modulators and related pharmaceutical agents.

The compound has been utilized in the synthesis of arylamino derivative estrogen receptor modulators, a class of molecules that interact with estrogen receptors to modulate hormonal signaling. These modulators are of particular interest for treating estrogen receptor-positive cancers and other hormone-responsive conditions. The fluorinated side chain can improve metabolic stability, bioavailability, and receptor selectivity, which are critical factors in drug development.

1-(3-Fluoropropyl)azetidin-3-amine serves primarily as a building block in multi-step synthetic sequences. Patents describe its incorporation into complex fused tricyclic compounds comprising substituted phenyl or pyridinyl moieties. For example, solid forms of tartrate salts of tricyclic tetrahydro-pyrido[3,4-b]indole derivatives have been synthesized using this azetidine intermediate. These derivatives demonstrate pharmacological activity as estrogen receptor modulators, offering potential therapeutic applications in cancer treatment.

The synthetic utility of 1-(3-Fluoropropyl)azetidin-3-amine stems from the reactivity of its amine group, which can form amide, urea, or carbamate linkages, and the azetidine ring, which provides a conformationally constrained scaffold that may enhance receptor binding. Its fluoropropyl side chain contributes to the lipophilicity and electron-withdrawing properties of the molecule, which can modulate the pharmacokinetics of the final drug candidates.

Applications reported in patents indicate the compound is used in the preparation of multiple pharmaceutical agents, including estrogen receptor modulators and related derivatives. The combination of fluorinated azetidine structures with substituted aromatic systems has been applied in the development of agents with improved potency and selectivity profiles. Patents covering these uses describe processes for creating solid forms suitable for formulation, enhancing stability, and controlling stereochemistry to optimize therapeutic effects.

Commercially, 1-(3-Fluoropropyl)azetidin-3-amine is available as a research chemical, and its role as a synthetic intermediate underscores its importance in modern medicinal chemistry. Its incorporation into drug candidates highlights the ongoing interest in fluorinated azetidines as scaffolds for bioactive compounds. While direct biological studies of 1-(3-Fluoropropyl)azetidin-3-amine itself are limited, its derivatives have been well-characterized, demonstrating the practical significance of this intermediate in pharmaceutical development.

In conclusion, 1-(3-Fluoropropyl)azetidin-3-amine represents a key intermediate in the synthesis of advanced pharmaceutical agents, particularly estrogen receptor modulators. Its chemical features—fluorinated side chain, azetidine ring, and reactive amine—make it a versatile building block for constructing bioactive molecules. The compound’s importance is reflected in multiple patents detailing its use in the preparation of therapeutically relevant tricyclic and fused heterocyclic derivatives. Its adoption in medicinal chemistry illustrates the strategic role of small, fluorinated cyclic amines in drug discovery and development.

References

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

WO-2023284837-A1 (2021) Arylamino derivative estrogen receptor modulator and use thereof. Link

US-11780834-B2 (2018) Solid forms of tricyclic tetrahydro-pyrido[3,4-b]indole compounds, processes for their preparation and methods of use. Link