5,7-Dichloro-8-fluoro-1H-pyrido[4,3-D]pyrimidine-2,4-dione
[CAS# 2836267-80-0]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound
• Name: 5,7-Dichloro-8-fluoro-1H-pyrido[4,3-D]pyrimidine-2,4-dione
• Molecular Formula: C₇H₂Cl₂FN₃O₂
• Molecular Weight: 250.01
• CAS Registry Number: 2836267-80-0
• SMILES: C12=C(C(=C(N=C1Cl)Cl)F)NC(=O)NC2=O

Properties

• Density: 1.8±0.1 g/cm³ Calc.^*
• Index of refraction: 1.598 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Discovery and Applications

5,7-Dichloro-8-fluoro-1H-pyrido[4,3-d]pyrimidine-2,4-dione is a halogenated heterocyclic compound that belongs to the class of pyridopyrimidines. This compound features a fused bicyclic core composed of a pyrimidine ring and a pyridine ring, substituted with chlorine and fluorine atoms at specific positions. Its structure provides a rigid scaffold with multiple sites amenable to chemical modification, which is valuable in medicinal chemistry for the development of biologically active derivatives.

The discovery of this compound stems from research into heterocyclic systems with potential pharmacological activity. Pyridopyrimidines have been studied extensively due to their ability to interact selectively with protein targets involved in cell signaling, enzyme regulation, and receptor binding. Halogen substituents, such as chlorine and fluorine, contribute to enhanced metabolic stability, lipophilicity, and binding affinity in drug candidates. These properties make 5,7-dichloro-8-fluoro-1H-pyrido[4,3-d]pyrimidine-2,4-dione a promising intermediate for the synthesis of inhibitors targeting proteins implicated in cancer, including KRAS G12D, as well as other enzymes and receptors in disease pathways.

In synthetic chemistry, this compound serves as a versatile building block. The chloro and fluoro groups can undergo nucleophilic substitution reactions, enabling the introduction of diverse functional groups. This versatility allows chemists to generate fused tricyclic or tetracyclic derivatives with optimized pharmacokinetic and pharmacodynamic profiles. Methods for preparing such derivatives typically involve stepwise functionalization of the pyridopyrimidine core, often including halogen exchange, amination, or condensation reactions to afford molecules with enhanced biological activity.

Applications of 5,7-dichloro-8-fluoro-1H-pyrido[4,3-d]pyrimidine-2,4-dione are primarily in drug discovery and medicinal chemistry research. It has been employed in the design of KRAS inhibitors, which are relevant for targeted cancer therapies. The compound’s rigid heterocyclic structure provides favorable interactions with enzyme active sites or protein interfaces, while halogen substituents enhance binding specificity. Beyond oncology, derivatives of this scaffold may also be explored for other therapeutic areas where modulation of enzyme or receptor activity is desired.

From a formulation standpoint, this compound can be converted into pharmaceutically acceptable salts or crystalline forms to improve solubility, stability, and bioavailability. Optimization of solid-state properties is critical when developing active pharmaceutical ingredients, and the chemical versatility of 5,7-dichloro-8-fluoro-1H-pyrido[4,3-d]pyrimidine-2,4-dione makes it suitable for such modifications. Overall, its combination of structural rigidity, chemical modifiability, and pharmacological potential underlines its importance in the development of novel therapeutic agents.

References

CN-118561872-A (2023) Pyrimidopyridine biological inhibitor, preparation method and application thereof. Link

WO-2024178304-A1 (2023) Kras modulators. Link

CN-118221699-A (2022) A pharmaceutically acceptable salt, crystal form and preparation method of a KRAS G12D inhibitor. Link