4-(4-Amino-3-fluorophenyl)morpholin-3-one
[CAS# 742073-22-9]

Identification

• Classification: Organic raw materials >> Ketone compound
• Name: 4-(4-Amino-3-fluorophenyl)morpholin-3-one
• Molecular Formula: C₁₀H₁₁FN₂O₂
• Molecular Weight: 210.20
• CAS Registry Number: 742073-22-9
• SMILES: C1COCC(=O)N1C2=CC(=C(C=C2)N)F

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 500.5±50.0 ºC 760 mmHg (Calc.)^*
• Flash point: 256.5±30.1 ºC (Calc.)^*
• Index of refraction: 1.588 (Calc.)^*

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

Discovory and Applicatios

4-(4-Amino-3-fluorophenyl)morpholin-3-one is a heterocyclic aromatic amine that has gained attention in medicinal chemistry as a versatile intermediate for the synthesis of biologically active compounds. Its structure features a morpholin-3-one ring, which is a six-membered oxygen- and nitrogen-containing heterocycle, fused with a substituted phenyl ring bearing a para-amino group and a meta-fluoro substituent. This combination of functional groups provides multiple points of chemical reactivity, making the compound useful for the development of drugs targeting a wide range of therapeutic areas.

The morpholin-3-one moiety is a rigid and polar heterocyclic scaffold that contributes to hydrogen-bonding interactions, solubility enhancement, and metabolic stability in drug molecules. It can act as both a hydrogen bond donor and acceptor, allowing interaction with protein targets, such as enzymes and receptors. The para-amino group on the phenyl ring is nucleophilic and reactive toward electrophiles, enabling modifications such as acylation, sulfonylation, and reductive alkylation. These transformations allow chemists to design derivatives with tailored pharmacological properties. The meta-fluoro substituent modulates electronic properties of the aromatic ring and often improves metabolic stability by resisting oxidative metabolism. Fluorine also influences lipophilicity, which can enhance membrane permeability and oral bioavailability.

From a synthetic perspective, 4-(4-amino-3-fluorophenyl)morpholin-3-one can be prepared through nucleophilic aromatic substitution or reductive amination of appropriately halogenated or nitro-substituted precursors. The morpholinone ring is typically introduced via cyclization reactions of amino alcohols or amino acids under controlled conditions. This flexibility in synthesis allows researchers to incorporate additional functional groups, forming fused heterocycles or larger polycyclic structures, which are valuable in drug discovery for kinase inhibitors, receptor modulators, or enzyme-targeted therapeutics.

Pharmacologically, compounds containing the 4-(4-amino-3-fluorophenyl)morpholin-3-one scaffold have potential activity in oncology, cardiovascular diseases, and central nervous system disorders. The para-amino group and morpholinone ring together facilitate interactions with enzyme active sites and receptor binding pockets. In particular, derivatives of this scaffold have been explored as inhibitors of estrogen receptors and other signaling proteins, showing promise for selective modulation of receptor activity. The fluorine atom can enhance binding affinity and selectivity by influencing hydrogen-bond networks and hydrophobic interactions within the target site.

The compound also has applications in the preparation of solid forms for pharmaceutical use. Its crystalline derivatives and salts can be optimized for solubility, stability, and bioavailability, which are critical factors in drug formulation. Patent literature indicates that derivatives of this scaffold have been utilized in the design of aryloxy, tetrahydroisoquinoline, and pyrido-indole compounds, highlighting its versatility as a building block for structurally diverse molecules with therapeutic potential.

Overall, 4-(4-amino-3-fluorophenyl)morpholin-3-one serves as an important intermediate in medicinal chemistry due to its reactive amino group, polar morpholinone ring, and fluorinated phenyl moiety. Its synthetic accessibility, chemical stability, and ability to undergo multiple derivatization reactions make it a valuable scaffold for developing novel drugs targeting diverse biological pathways. The combination of electronic modulation, metabolic stability, and hydrogen-bonding capacity ensures that derivatives of this compound can be fine-tuned for optimal pharmacokinetic and pharmacodynamic profiles.

References

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

EP-4371977-A1 (2021) Arylamino derivative estrogen receptor modulator and use thereof. Link

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