2-Amino-6-bromo-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one
[CAS# 1637781-10-2]

Identification

• Classification: Organic raw materials >> Ketone compound
• Name: 2-Amino-6-bromo-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one
• Molecular Formula: C₁₃H₁₅BrN₄O
• Molecular Weight: 323.19
• CAS Registry Number: 1637781-10-2
• SMILES: CC1=C(C(=O)N(C2=NC(=NC=C12)N)C3CCCC3)Br

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Boiling point: 494.6±55.0 ºC 760 mmHg (Calc.)^*
• Flash point: 252.9±31.5 ºC (Calc.)^*
• Solubility: water: Practically insoluble (0.094 g/L) (25 ºC), Calc.
• Index of refraction: 1.688 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2016 ACD/Labs)

Discovory and Applicatios

2-Amino-6-bromo-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one is a heterocyclic compound that belongs to the pyrido[2,3-d]pyrimidinone class. Its structure contains a fused bicyclic system combining a pyridine and a pyrimidine ring, with a ketone group at position 7 and a hydrogen at position 8, forming the 7(8H)-one tautomer. Substituents on this scaffold include an amino group at position 2, a bromine atom at position 6, a methyl group at position 5, and a cyclopentyl group at position 8. The molecular formula is C₁₄H₁₆BrN₃O, reflecting the presence of three nitrogen atoms in the bicyclic system, one bromine, one oxygen, and the hydrocarbon substituents. The compound is relatively rigid due to the fused ring system, while the cyclopentyl and methyl groups confer steric bulk that can influence its interaction with biological targets.

The discovery of substituted pyrido[2,3-d]pyrimidinones has been historically linked to the search for kinase inhibitors and other biologically active heterocycles. Compounds of this class are valued in medicinal chemistry for their planar heteroaromatic core and capacity for substitution at multiple positions, allowing fine-tuning of electronic and steric properties. The amino group at position 2 provides a site for hydrogen bonding and enhances solubility, while the bromine atom at position 6 can be used in cross-coupling reactions or serves as a halogen bond donor in molecular recognition. The methyl group at position 5 adds hydrophobic character, and the cyclopentyl ring at position 8 introduces conformational rigidity and additional hydrophobic surface area.

From a synthetic perspective, the preparation of 2-amino-6-bromo-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one typically starts with appropriately substituted pyrimidine or pyridine precursors. One common strategy involves the condensation of a 2-aminopyridine derivative with a functionalized β-ketoester or nitrile to construct the fused bicyclic core. Bromination can be introduced either on the pyrimidine ring prior to cyclization or post-cyclization at position 6 using selective halogenation methods. The methyl and cyclopentyl groups are incorporated through alkylation of precursors or by using pre-substituted starting materials. Protective groups may be employed to prevent unwanted side reactions during cyclization or halogenation. The final compound is typically isolated as a solid after recrystallization or chromatography.

In practical application, this compound is primarily a building block or lead scaffold in medicinal chemistry programs. Its fused bicyclic system allows it to act as a kinase hinge-binding motif, and the substituents can be modified to optimize binding affinity and selectivity. The amino group and ketone facilitate hydrogen bonding interactions in enzyme active sites, while the bromine atom enables further functionalization for structure-activity relationship studies. Cyclopentyl and methyl substituents are used to modulate lipophilicity and steric complementarity with binding pockets. Because of its rigidity and planar geometry, the compound is suitable for fragment-based drug design or as a template for generating libraries of derivatives.

The compound’s chemical stability is influenced by the bromine atom and the amino group, which can participate in nucleophilic or electrophilic reactions under harsh conditions. In general, it is stable under standard laboratory storage conditions at ambient temperature, protected from strong acids or bases that could hydrolyze the ketone or displace the bromine. Solubility is moderate in polar organic solvents and slightly lower in aqueous buffers, but the presence of the amino group can enhance solubility in acidic aqueous media due to salt formation.

Historically, pyrido[2,3-d]pyrimidinones have been explored for multiple pharmacological applications, including kinase inhibition, antiviral, and anticancer activities. The ability to introduce diverse substituents at strategic positions allows chemists to tailor electronic properties, steric profile, and hydrogen bonding capacity. 2-Amino-6-bromo-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one exemplifies this approach, combining a planar, nitrogen-rich core with functional substituents that provide both reactivity and specific molecular recognition features.

This compound continues to be relevant as a synthetic intermediate and structural scaffold in research programs seeking to develop heterocyclic inhibitors and small molecules with defined biological activity. Its combination of planarity, nitrogen heteroatoms, and strategically positioned substituents make it a versatile candidate for chemical biology and medicinal chemistry studies.

References

2020. 2-amino-pyrido[2,3-d]pyrimidin-7(8h)-one derivatives as cdk inhibitors and uses thereof. European Patent Office.
URL: EP-3172214-B1

2017. 2-amino-pyrido[2,3-D]pyrimidin-7(8H)-one derivatives as CDK inhibitors and uses thereof. United States Patent and Trademark Office.
URL: US-9828373-B2

2015. 2-amino-pyrido[2,3-d]pyrimidin-7(8h)-one derivatives as cdk inhibitors and uses thereof. World Intellectual Property Organization.
URL: WO-2016015598-A1