5-Amino-4-chloropyrimidine
[CAS# 54660-78-5]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Chloropyrimidine
• Name: 5-Amino-4-chloropyrimidine
• Synonyms: 4-chloropyrimidin-5-amine
• Molecular Formula: C₄H₄ClN₃
• Molecular Weight: 129.55
• CAS Registry Number: 54660-78-5
• EC Number: 640-720-8
• SMILES: C1=C(C(=NC=N1)Cl)N

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Melting point: 111 - 116 ºC (Expl.)
• Boiling point: 253.8±20.0 ºC 760 mmHg (Calc.)^*
• Flash point: 107.3±21.8 ºC (Calc.)^*
• Index of refraction: 1.618 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Hazard Statements: H302-H318
• Precautionary Statements: P264-P264+P265-P270-P280-P301+P317-P305+P354+P338-P317-P330-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Serious eye damage	Eye Dam.	1	H318
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319

Discovory and Applicatios

5-Amino-4-chloropyrimidine is a halogenated heterocyclic compound with the molecular formula C₄H₄ClN₃. It is a substituted pyrimidine in which an amino group is attached at the 5-position and a chlorine atom at the 4-position. Compounds of this type were first studied extensively in the mid-20th century during the development of heterocyclic chemistry, particularly for their relevance in nucleic acid analogues and pharmaceutical intermediates. The electron-withdrawing effect of the chlorine atom combined with the electron-donating amino group provides unique reactivity, making the compound a versatile building block in organic synthesis.

5-Amino-4-chloropyrimidine is primarily used as an intermediate in the synthesis of pharmaceuticals. It is valuable for constructing substituted pyrimidine derivatives, which are key scaffolds in many drugs, including antiviral, anticancer, and antimicrobial agents. The chlorine atom serves as a reactive site for nucleophilic substitution, allowing for selective introduction of various functional groups such as alkyl, aryl, or heteroaryl substituents. This enables the design of diverse molecules with optimized pharmacological properties.

In medicinal chemistry, 5-amino-4-chloropyrimidine has been employed to synthesize kinase inhibitors, antiviral nucleoside analogues, and other bioactive compounds targeting enzymes or receptors. The pyrimidine core is crucial for molecular recognition in biological systems, while the amino and chloro substituents allow further chemical modifications to enhance potency, selectivity, and metabolic stability. Its use as a building block enables efficient access to complex molecules with therapeutic relevance.

The compound is also used in agrochemical research for the preparation of pyrimidine-based herbicides, fungicides, and insecticides. Substitution at the 4- and 5-positions allows for tuning of electronic and steric properties, which can influence biological activity and environmental stability. Fluorinated or alkylated derivatives derived from 5-amino-4-chloropyrimidine have been explored to improve efficacy and persistence of agrochemical products.

In addition to pharmaceuticals and agrochemicals, 5-amino-4-chloropyrimidine finds application in heterocyclic chemistry research. It serves as a model compound for studying reactivity patterns of substituted pyrimidines, including nucleophilic aromatic substitution, condensation, and cyclization reactions. Its reactivity profile makes it a useful reagent for constructing fused heterocycles, pyrimidine-containing ligands, and other functionalized heterocyclic compounds.

The discovery and continued use of 5-amino-4-chloropyrimidine highlight its importance as a versatile heterocyclic intermediate. Its combination of nucleophilic and electrophilic reactive sites allows for selective modification and functionalization, supporting applications in pharmaceuticals, agrochemicals, and heterocyclic chemistry research. The compound exemplifies how substituted pyrimidines can serve as key building blocks for biologically active and industrially relevant molecules.

References

2017. Pushing the Limits of Detection of Weak Binding Using Fragment-Based Drug Discovery: Identification of New Cyclophilin Binders. Journal of Molecular Biology, 429(16).
DOI: 10.1016/j.jmb.2017.06.016

1983. Synthesis of 4-chloro-1,2,3-triazole derivatives by diazotization of 6-substituted 5-amino-4-chloropyrimidines. Chemistry of Heterocyclic Compounds, 19(10).
DOI: 10.1007/bf00505769

2016. Recent advances in the synthesis and applications of oxazolo[5,4-d]pyrimidines (microreview). Chemistry of Heterocyclic Compounds, 52(10).
DOI: 10.1007/s10593-016-1965-9