9,10-Dimethoxy-2-(2,4,6-trimethylanilino)-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one
[CAS# 76536-66-8]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Isoquinoline compound
• Name: 9,10-Dimethoxy-2-(2,4,6-trimethylanilino)-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one
• Synonyms: 2-(Mesitylamino)-9,10-dimethoxy-6,7-dihydro-4H-pyrimido[6,1-a]isoquinolin-4-one
• Molecular Formula: C₂₃H₂₅N₃O₃
• Molecular Weight: 391.46
• CAS Registry Number: 76536-66-8
• SMILES: CC1=CC(=C(C(=C1)C)NC2=NC(=O)N3CCC4=CC(=C(C=C4C3=C2)OC)OC)C

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 559.2±60.0 ºC 760 mmHg (Calc.)^*
• Flash point: 292.0±32.9 ºC (Calc.)^*
• Index of refraction: 1.624 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319
• Precautionary Statements: P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Discovory and Applicatios

9,10-Dimethoxy-2-(2,4,6-trimethylanilino)-6,7-dihydropyrimido\[6,1-a]isoquinolin-4-one is a synthetic heterocyclic compound that belongs to the pyrimido\[6,1-a]isoquinolinone family, a group of fused polycyclic systems combining the pyrimidine and isoquinoline frameworks. This structural class is of interest in medicinal chemistry because it integrates two heterocyclic motifs that are frequently encountered in biologically active molecules. The compound is further characterized by a 9,10-dimethoxy substitution pattern, a 2-(2,4,6-trimethylanilino) substituent, and a partially saturated 6,7-dihydro moiety, all of which influence its electronic and steric properties.

The discovery of pyrimido\[6,1-a]isoquinolinones emerged during mid-20th-century research into fused heteroaromatic scaffolds as potential bioactive agents. Isoquinoline derivatives are widespread in natural products, especially alkaloids, while pyrimidine rings play a central role in nucleobases and numerous therapeutic agents. By fusing these two heterocycles, researchers generated new molecular backbones for drug discovery, aiming to explore anticancer, antimicrobial, and enzyme-inhibitory activities. Within this context, 9,10-dimethoxy-2-(2,4,6-trimethylanilino)-6,7-dihydropyrimido\[6,1-a]isoquinolin-4-one represents a more elaborated derivative designed to test how different substituents modulate biological activity.

Synthetic approaches to this compound typically begin with isoquinoline or tetrahydroisoquinoline intermediates. The introduction of the 9,10-dimethoxy groups is often achieved via methylation of catechol functionalities, whereas the fused pyrimidine ring can be constructed through condensation of urea or guanidine derivatives with appropriately substituted precursors. The incorporation of the 2-(2,4,6-trimethylanilino) substituent is achieved via nucleophilic substitution or amination, and the sterically demanding trimethyl-substituted aniline group plays a significant role in shaping the molecule’s steric profile and its potential interaction with biological targets.

Applications of this compound are primarily of interest in medicinal chemistry research. Pyrimidoisoquinolinones have been studied for a range of pharmacological activities, including cytotoxic, antimicrobial, and enzyme-inhibitory effects. The presence of the dimethoxy groups at the 9- and 10-positions enhances electron density on the aromatic system, potentially influencing binding affinity to enzymes or receptors, while also affecting metabolic stability. The bulky 2,4,6-trimethyl substitution on the aniline group increases steric hindrance, which may confer selectivity in binding or reduce susceptibility to metabolic degradation.

Although specific biological activity data for 9,10-dimethoxy-2-(2,4,6-trimethylanilino)-6,7-dihydropyrimido\[6,1-a]isoquinolin-4-one is limited, related analogs in the pyrimidoisoquinolinone series have shown promise as kinase inhibitors, DNA-interacting agents, and antimicrobial candidates. The design rationale for including a bulky, electron-rich anilino substituent is often to enhance interactions with hydrophobic or aromatic binding sites, while also modulating solubility and pharmacokinetics.

Beyond pharmacological relevance, the compound also holds value in synthetic organic chemistry as a model for exploring substitution patterns and reactivity in fused heteroaromatic frameworks. The presence of both methoxy groups and a sterically hindered aniline substituent provides an opportunity to study how electronic and steric effects influence synthetic pathways, reaction yields, and functional group compatibility. Such studies contribute to broader efforts in heterocyclic chemistry, where fine-tuning substituents is critical for generating compounds with desired physical and biological properties.

In conclusion, 9,10-dimethoxy-2-(2,4,6-trimethylanilino)-6,7-dihydropyrimido\[6,1-a]isoquinolin-4-one is a representative example of a highly substituted pyrimidoisoquinolinone derivative, designed within the context of heterocyclic scaffold exploration for drug discovery. While its direct applications remain largely at the research stage, its synthesis and structural features highlight the strategies used to develop novel compounds with potential anticancer or antimicrobial activity. It also serves as a useful subject for studying substitution effects in complex fused heterocycles, contributing to the broader field of medicinal and synthetic chemistry.