4-Aminopyrazolo[3,4-d]pyrimidine
[CAS# 2380-63-4]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Aminopyrimidine
• Name: 4-Aminopyrazolo[3,4-d]pyrimidine
• Synonyms: 1H-Pyrazolo[3,4-d]pyrimidin-4-amine
• Molecular Formula: C₅H₅N₅
• Molecular Weight: 135.13
• CAS Registry Number: 2380-63-4
• EC Number: 219-174-6
• SMILES: C1=NNC2=NC=NC(=C21)N

Properties

• Density: 1.1$+/-$0.1 g/cm³ Calc.^*
• Melting point: 325 $degree$C (Expl.)
• Boiling point: 266.3$+/-$40.0 $degree$C 760 mmHg (Calc.)^*
• Flash point: 132.6$+/-$30.9 $degree$C (Calc.)^*
• Index of refraction: 1.487 (Calc.)^*

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

Safety Data

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

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315

• Transport Information: UN 2811

Discovery and Applications

4-Aminopyrazolo[3,4-d]pyrimidine is a fused heterocyclic compound composed of a pyrazole ring fused to a pyrimidine, with an amino group at the 4-position of the pyrimidine ring. Compounds of this structural class have been studied extensively in medicinal chemistry because the pyrazolopyrimidine scaffold is recognized as a privileged structure for interaction with biologically important targets, particularly kinases and enzymes involved in nucleic acid metabolism. The combination of aromaticity, hydrogen-bonding potential, and a planar bicyclic framework makes this molecule an important building block in drug design and synthetic chemistry. The discovery of pyrazolopyrimidine derivatives dates back to investigations of heterocyclic nucleobase analogs and early kinase inhibitors. 4-Aminopyrazolo[3,4-d]pyrimidine, in particular, was identified as a key scaffold in the development of enzyme inhibitors because the fused bicyclic system mimics purine nucleotides, allowing it to occupy ATP-binding sites in kinases or act as a competitive inhibitor in nucleotide-processing enzymes. The amino substituent at the 4-position provides hydrogen-bonding capacity, which is critical for molecular recognition and binding affinity. Synthetically, 4-aminopyrazolo[3,4-d]pyrimidine is typically prepared through condensation reactions of suitably substituted hydrazines with beta-dicarbonyl compounds or amidines to form the pyrazole ring, followed by cyclization with appropriate nitrogen-containing reagents to generate the pyrimidine fusion. The amino group can be introduced either via direct amination or by hydrolysis of a precursor nitrile or nitro group. These methods allow selective functionalization while preserving the structural integrity of the fused heterocycle, enabling the production of high-purity material for research or pharmaceutical use. This compound has been widely applied in medicinal chemistry as a scaffold for kinase inhibitors. The planar bicyclic structure allows it to fit into the ATP-binding pocket of various kinases, while the amino group can form hydrogen bonds with conserved residues in the hinge region of the enzyme. Researchers have developed multiple analogs based on 4-aminopyrazolo[3,4-d]pyrimidine to improve potency, selectivity, and pharmacokinetic properties, contributing to the development of targeted therapies for cancer and inflammatory diseases. In addition to kinase inhibition, derivatives of 4-aminopyrazolo[3,4-d]pyrimidine have been explored as potential inhibitors of other enzymes such as phosphotransferases, polymerases, and nucleotidyl cyclases. The fused heterocyclic system allows for π–π stacking and hydrogen-bonding interactions with biological targets, while chemical modifications at various positions on the pyrazolopyrimidine core provide opportunities to modulate electronic, steric, and pharmacokinetic properties. Beyond biological applications, 4-aminopyrazolo[3,4-d]pyrimidine is a versatile intermediate in organic synthesis. It can undergo alkylation, acylation, and cross-coupling reactions to produce substituted derivatives for chemical libraries or more complex heterocyclic systems. The amino group serves as a reactive site for derivatization, while the bicyclic core provides structural rigidity and planarity that are valuable in constructing molecules with defined geometry for both chemical and pharmaceutical studies. Overall, 4-aminopyrazolo[3,4-d]pyrimidine exemplifies a biologically and synthetically important fused heterocyclic scaffold. Its combination of planar structure, amino functionality, and pyrazolopyrimidine core enables applications in kinase inhibition, enzyme modulation, and organic synthesis, making it a key building block in medicinal chemistry and drug development research.

References

2024. Arylglyoxal-based multicomponent synthesis of C-3 functionalized imidazoheterocycles. Chemical Papers.
DOI: 10.1007/s11696-024-03674-1

2023. Fragment-to-Lead Medicinal Chemistry Publications in 2021. Journal of Medicinal Chemistry.
DOI: 10.1021/acs.jmedchem.2c01827

2021. Design and Synthesis of Pyrrolo[2,3-d]pyrimidine-Derived Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Checkpoint Kinase 1 (CHK1)-Derived Crystallographic Surrogate. Journal of Medicinal Chemistry.
DOI: 10.1021/acs.jmedchem.1c00720