4-chloro-5,5-dimethyl-5H,6H,7H-pyrrolo[2,3-d]pyrimidin-6-one
[CAS# 1226804-02-9]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound
• Name: 4-chloro-5,5-dimethyl-5H,6H,7H-pyrrolo[2,3-d]pyrimidin-6-one
• Molecular Formula: C₈H₈ClN₃O
• Molecular Weight: 197.62
• CAS Registry Number: 1226804-02-9
• SMILES: CC1(C2=C(NC1=O)N=CN=C2Cl)C

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 372.7±42.0 °C 760 mmHg (Calc.)^*
• Flash point: 179.2±27.9 °C (Calc.)^*
• Index of refraction: 1.558 (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

4-Chloro-5,5-dimethyl-5H,6H,7H-pyrrolo[2,3-d]pyrimidin-6-one is a fused bicyclic heterocycle belonging to the pyrrolopyrimidine class, characterized by a chlorine atom at position 4 and two methyl groups at position 5. This core structure combines a pyrrole ring fused to a pyrimidine moiety, forming a rigid, planar scaffold that is valuable for medicinal chemistry applications.

The compound has been explored in the development of tetrahydropyrrolopyrazole and other condensed bicyclic derivatives. Its structure provides a versatile platform for chemical modifications, enabling the introduction of functional groups via halogen substitution, cross-coupling reactions, or amide formation. Such modifications are crucial for tuning biological activity, selectivity, and pharmacokinetic properties.

Synthetic methods typically involve cyclization of suitably substituted pyrimidine precursors with nitrogen nucleophiles or enamine derivatives, followed by functional group manipulation to install the chlorine and methyl groups. These strategies have allowed the preparation of a wide range of derivatives with potential applications in oncology, kinase inhibition, and other therapeutic areas.

Biologically, 4-chloro-5,5-dimethyl-5H,6H,7H-pyrrolo[2,3-d]pyrimidin-6-one derivatives have been investigated as PKB (protein kinase B) inhibitors and other enzyme modulators. The fused bicyclic system allows strong π–π interactions and hydrogen bonding with enzyme active sites, while the chlorine atom can contribute to halogen bonding and modulate metabolic stability. Methyl substitutions at position 5 improve steric protection and influence lipophilicity, which can enhance cell permeability and bioavailability.

Pharmaceutical development of this scaffold includes exploration of crystalline and salt forms to optimize solubility, stability, and formulation properties. Patents indicate broad interest in its use as a core for designing novel kinase inhibitors, tetrahydropyrrolopyrazole derivatives, and other fused bicyclic bioactive compounds. Its versatility in medicinal chemistry makes it a highly valuable intermediate for drug discovery programs.

References

CN-113444110-B (2023) Tetrahydropyrrolopyrazole derivatives, preparation method and application in medicine. Link

CN-115397815-B (2024) Fused bicyclic derivatives, preparation methods and pharmaceutical applications. Link

EP-3459953-A1 (2016) Novel 5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one derivatives and methods of preparation. Link