3-Fluoro-4-morpholinophenylboronic Acid | CAS 279262-09-8 | ≥95%

Suzuki–Miyaura cross-coupling reactions: 3-Fluoro-4-morpholinophenylboronic acid is a bifunctional heteroaryl-substituted boronic acid used in palladium-catalysed Suzuki–Miyaura cross-coupling reactions. It introduces a 3-fluoro-4-morpholinophenyl fragment — a pharmacologically privileged motif — into target molecules in a single synthetic step via carbon–carbon bond formation with aryl and heteroaryl halides or pseudohalides.

PI3K and mTOR kinase inhibitor synthesis: The 3-fluoro-4-morpholinophenyl motif is a key pharmacophore in the development of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitors. The morpholine nitrogen acts as a hydrogen bond acceptor that engages the hinge region of the PI3K ATP-binding site, while the fluorine atom modulates lipophilicity and metabolic stability. Patent literature (e.g., US9801888) describes the 3-fluoro-4-morpholinophenyl urea fragment as a structural component in pyrimidine-based mTOR and PI3K inhibitors, where the boronic acid serves as the Suzuki coupling precursor for its incorporation.

Morpholinopyrimidine-based anticancer agents: Morpholinopyrimidine derivatives are a major structural class in oncology drug discovery, with multiple clinical-stage compounds targeting the PI3K/AKT/mTOR signalling pathway. 3-Fluoro-4-morpholinophenylboronic acid provides a convergent route to introducing the morpholino-fluoroaryl unit via cross-coupling, enabling rapid analogue generation in structure–activity relationship studies around these scaffolds.

Drug discovery building block: This compound is classified as a drug discovery intermediate by multiple suppliers. The combination of three features — boronic acid reactivity for cross-coupling, the morpholine ring for hydrogen bond acceptor capability and improved aqueous solubility, and the ortho-fluorine for metabolic blocking and conformational effects — makes it a versatile building block for medicinal chemistry programmes targeting kinases and other ATP-binding proteins.

Fluorine as a metabolic blocker: The fluorine atom at the 3-position (ortho to morpholine) serves as a metabolic blocker, reducing oxidative defluorination and aromatic hydroxylation at that position by cytochrome P450 enzymes. This is a well-established medicinal chemistry strategy for improving metabolic stability and oral bioavailability of drug candidates containing aniline or morpholinoaryl fragments.

Structure–activity relationship exploration: The compound enables systematic SAR studies comparing fluorinated versus non-fluorinated morpholinophenyl analogues. The availability of this boronic acid allows researchers to directly evaluate the effect of ortho-fluorine substitution on target binding, selectivity, ADMET properties, and in vivo efficacy within a matched molecular pair framework.