3-(4-Phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
[CAS# 330786-24-8]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Amine
• Name: 3-(4-Phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
• Molecular Formula: C₁₇H₁₃N₅O
• Molecular Weight: 303.32
• CAS Registry Number: 330786-24-8
• EC Number: 810-090-0
• SMILES: C1=CC=C(C=C1)OC2=CC=C(C=C2)C3=C4C(=NC=NC4=NN3)N

Properties

• Solubility: Insoluble (1.2E^-3 g/L) (25 $degree$C), Calc.^*
• Density: 1.380$+/-$0.06 g/cm³ (20 $degree$C 760 Torr), Calc.^*
• Boiling point: 577.4$+/-$50.0 $degree$C 760 mmHg (Calc.)^*
• Flash point: 303.0$+/-$30.1 $degree$C (Calc.)^*
• Index of refraction: 1.734 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06;GHS07;GHS09 Danger
• Risk Statements: H301-H302-H315-H319-H335-H400-H410
• Safety Statements: P261-P264-P264+P265-P270-P271-P273-P280-P301+P316-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400

Discovery and Applications

3-(4-Phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine is a fused heterocyclic compound that integrates a pyrazolopyrimidine scaffold with a substituted biaryl moiety. Pyrazolo[3,4-d]pyrimidines are well-known in medicinal chemistry as privileged structures for the design of kinase inhibitors and other bioactive molecules because their bicyclic framework mimics purine nucleobases, enabling interactions with ATP-binding sites of enzymes and receptors. The attachment of a 4-phenoxyphenyl group at the 3-position provides additional aromaticity and potential for π–π stacking and hydrophobic interactions, while the amino group at the 4-position allows hydrogen bonding with biological targets. The molecular structure consists of a fused five- and six-membered ring system with a nitrogen-rich pyrazole and pyrimidine ring. The 4-phenoxy substituent is linked via an ether bond to a phenyl ring, which increases lipophilicity and extends the conjugated system. The amino group at the 4-position of the pyrazolopyrimidine core contributes both nucleophilicity and the ability to form hydrogen bonds with amino acid residues in enzymes, enhancing binding affinity and selectivity in drug-target interactions. This combination of electronic, steric, and hydrogen-bonding properties makes the compound a versatile scaffold for the development of pharmacologically active derivatives. Synthetically, 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine is typically prepared by constructing the pyrazolopyrimidine core through condensation reactions of substituted hydrazines with suitable 1,3-dicarbonyl compounds, followed by cyclization with amidine or nitrile derivatives. The biaryl ether moiety can be introduced via palladium-catalyzed cross-coupling reactions, such as Suzuki or Buchwald–Hartwig couplings, allowing precise installation of the 4-phenoxyphenyl group at the 3-position. The amino group may be present from the precursor or introduced via selective amination reactions, ensuring its position on the pyrimidine ring is retained. In medicinal chemistry, pyrazolopyrimidine derivatives with biaryl substituents are particularly explored as kinase inhibitors. The planar bicyclic system allows the compound to fit into ATP-binding pockets, and the amino group can form key hydrogen bonds with conserved residues in the hinge region of kinases. The phenoxyphenyl substituent increases hydrophobic contact and improves selectivity toward specific kinase isoforms. This structural combination has been leveraged to develop molecules with activity against cancer-associated kinases, inflammatory kinases, and other therapeutically relevant enzyme families. Beyond enzyme inhibition, the compound serves as a synthetic intermediate for further functionalization. The amino group can be modified through acylation, sulfonylation, or alkylation, and the phenoxy group allows additional substitution on the aromatic ring system. These chemical transformations expand the diversity of derivatives for structure–activity relationship studies and allow fine-tuning of pharmacokinetic properties, solubility, and binding specificity. Overall, 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine exemplifies a functionalized pyrazolopyrimidine scaffold that combines a fused heterocyclic core, a hydrogen-bonding amino group, and an extended aromatic substituent. Its structural characteristics make it valuable for kinase inhibition research, drug discovery, and the synthesis of complex heterocyclic derivatives, highlighting its significance as both a biologically active molecule and a versatile synthetic intermediate.

References

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