2-Chloro-6,7-dihydro-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquinolin-4-one
[CAS# 75535-96-5]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Isoquinoline compound
• Name: 2-Chloro-6,7-dihydro-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquinolin-4-one
• Synonyms: 2-Chloro-9,10-dimethoxy-6,7-dihydro-4H-pyrimido[6,1-a]isoquinolin-4-one
• Molecular Formula: C₁₄H₁₃ClN₂O₃
• Molecular Weight: 292.72
• CAS Registry Number: 75535-96-5
• EC Number: 179-731-3
• SMILES: COC1=C(C=C2C(=C1)CCN3C2=CC(=NC3=O)Cl)OC

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 470.0±55.0 ºC 760 mmHg (Calc.)^*
• Flash point: 238.1±31.5 ºC (Calc.)^*
• Index of refraction: 1.641 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P304+P340-P305+P351+P338-P319-P330-P337+P317-P403+P233-P405-P501

Discovory and Applicatios

2-Chloro-6,7-dihydro-9,10-dimethoxy-4H-pyrimido\[6,1-a]isoquinolin-4-one is a synthetic heterocyclic compound that belongs to the class of pyrimidoisoquinolinones. This scaffold combines a pyrimidine moiety fused to an isoquinoline framework, creating a rigid polycyclic system with pharmacological relevance. The presence of the chloro substituent at the 2-position and the dimethoxy groups at the 9- and 10-positions further modifies the molecule’s physicochemical and biological properties, while the partially saturated 6,7-dihydro ring confers additional conformational flexibility compared to fully aromatic analogs.

The discovery of this compound is closely linked to systematic research into isoquinoline and pyrimidine-fused heterocycles, many of which emerged from efforts in the mid to late 20th century to identify new scaffolds with anticancer, antimicrobial, or central nervous system activities. Isoquinoline derivatives are widely recognized in natural products such as alkaloids, while pyrimidines are core structural elements in many biologically active molecules, including nucleobases and pharmaceuticals. The fusion of these two motifs in the pyrimido\[6,1-a]isoquinolinone system provided chemists with a novel platform for exploring bioactivity.

The synthesis of 2-chloro-6,7-dihydro-9,10-dimethoxy-4H-pyrimido\[6,1-a]isoquinolin-4-one generally involves multistep routes beginning with suitably substituted isoquinoline or tetrahydroisoquinoline precursors. The incorporation of dimethoxy groups can be achieved by methylation of catechol intermediates, while the chloro substituent is introduced through electrophilic substitution or halogenation reactions. The construction of the fused pyrimidine ring is often accomplished through condensation reactions involving urea or guanidine derivatives, enabling the closure of the bicyclic system that defines the pyrimidoisoquinolinone skeleton.

Applications of this compound and its structural analogs are primarily in the field of medicinal chemistry. Pyrimidoisoquinolinones have been reported to exhibit a variety of biological activities, including anticancer, antimicrobial, and enzyme inhibitory effects, depending on the nature of their substituents. The 2-chloro group is of particular interest because it increases lipophilicity and can enhance interactions with hydrophobic pockets in biological targets, while also serving as a reactive site for further chemical modification via substitution reactions. The dimethoxy groups at the 9- and 10-positions can contribute to electron distribution across the aromatic system and may influence both metabolic stability and binding affinity.

Although detailed pharmacological evaluation of 2-chloro-6,7-dihydro-9,10-dimethoxy-4H-pyrimido\[6,1-a]isoquinolin-4-one specifically is limited, studies of related compounds within the same chemical class suggest potential utility in drug discovery. For example, pyrimidoisoquinolinones have been investigated as inhibitors of kinases and topoisomerases, enzymes frequently targeted in anticancer therapy. Others have shown promise as antimicrobial agents by interfering with nucleic acid synthesis or enzyme activity.

Beyond pharmacology, the structural complexity of this compound also makes it an interesting subject for synthetic organic chemistry. Its fused heterocyclic framework provides a platform for exploring reactivity, substitution patterns, and functional group compatibility in multi-step synthetic strategies. The chloro substituent offers a functional handle for derivatization, making the compound a potentially useful intermediate in the synthesis of more elaborated analogs with tailored biological properties.

In conclusion, 2-chloro-6,7-dihydro-9,10-dimethoxy-4H-pyrimido\[6,1-a]isoquinolin-4-one is a representative member of the pyrimidoisoquinolinone family, notable for its polycyclic fused heteroaromatic core and functional substituents. While it is not yet a widely applied compound in industry or medicine, its design reflects systematic efforts in heterocyclic chemistry to expand the range of bioactive scaffolds available for drug discovery. Its potential applications lie primarily in medicinal chemistry as a candidate for anticancer or antimicrobial studies, as well as in synthetic chemistry as a versatile intermediate for further derivatization.