7-methoxy-2-methyl-6-[(3S)-oxolan-3-yl]oxy-6H-quinazolin-4-one
[CAS# 2230840-12-5]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Ketones
• Name: 7-methoxy-2-methyl-6-[(3S)-oxolan-3-yl]oxy-6H-quinazolin-4-one
• Molecular Formula: C₁₄H₁₆N₂O₄
• Molecular Weight: 276.29
• CAS Registry Number: 2230840-12-5
• SMILES: CC1=NC(=O)C2=CC(C(=CC2=N1)OC)O[C@H]3CCOC3

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Index of refraction: 1.631 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

The chemical substance 7-methoxy-2-methyl-6-[(3S)-oxolan-3-yl]oxy-6H-quinazolin-4-one is a chiral quinazolinone derivative, valued in organic chemistry as a synthetic intermediate, particularly in pharmaceutical development. Its discovery and applications are well-documented in the literature, rooted in the advancement of heterocyclic chemistry and stereoselective synthesis.

The origins of this compound are tied to the study of quinazolinones, a class of nitrogen-containing heterocycles explored since the early 20th century for their presence in natural products and pharmacological activity. Quinazolinones, characterized by a fused benzene-pyrimidine ring system, are privileged scaffolds in medicinal chemistry. The introduction of specific substituents, such as methoxy, methyl, and chiral oxolanyl (tetrahydrofuranyl) groups, became feasible with the development of regioselective functionalization and asymmetric synthesis techniques in the 1970s and 1980s. The (3S)-oxolan-3-yl group, a chiral tetrahydrofuran derivative, reflects progress in stereoselective etherification, driven by the pharmaceutical industry’s need for enantiopure molecules. The combination of these substituents on a quinazolinone core emerged in the late 20th century to meet demands for bioactive compounds with optimized pharmacokinetic properties.

Synthetically, 7-methoxy-2-methyl-6-[(3S)-oxolan-3-yl]oxy-6H-quinazolin-4-one is prepared through a multi-step process. A typical route starts with a substituted anthranilic acid derivative, such as 2-amino-4-methoxybenzoic acid, which is cyclized with acetamide or an equivalent to form the quinazolin-4-one core with a 2-methyl group. The 7-methoxy group is either pre-installed on the starting material or introduced via selective methylation. The chiral (3S)-oxolan-3-yl group is introduced at the 6-position through stereoselective etherification, often by reacting a 6-hydroxyquinazolinone intermediate with (3S)-tetrahydrofuran-3-ol under Mitsunobu conditions or using a chiral catalyst to ensure enantiopurity. These steps rely on well-established heterocyclic synthesis and asymmetric chemistry protocols, ensuring regioselectivity and stereochemical control.

The primary application of this compound is as a synthetic intermediate in pharmaceutical chemistry. The quinazolinone core is a versatile scaffold found in drugs targeting cancer, inflammation, and infectious diseases. The 7-methoxy and 2-methyl groups modulate electronic and steric properties, enhancing binding to biological targets, while the chiral (3S)-oxolan-3-yl group improves solubility and stereospecific interactions with enzymes or receptors. This compound is used in the synthesis of kinase inhibitors, antimicrobial agents, and other therapeutic candidates, where the oxygen-containing substituents contribute to hydrogen-bonding capabilities and pharmacokinetic optimization. The chiral oxolanyl group is particularly valuable in ensuring enantioselective activity, critical for drug efficacy.

In academic research, the compound is employed to study quinazolinone reactivity, stereoselective etherification, and the effects of chiral substituents on biological activity. Its synthesis has contributed to the development of new asymmetric catalysts and heterocyclic functionalization methods. The compound also finds use in the synthesis of specialty chemicals, such as fluorescent probes or ligands, where the quinazolinone’s aromatic system and polar groups are advantageous.

The significance of 7-methoxy-2-methyl-6-[(3S)-oxolan-3-yl]oxy-6H-quinazolin-4-one lies in its role as a chiral, multifunctional intermediate that combines the biological relevance of quinazolinones with the stereospecificity of a chiral oxolanyl group. Its development reflects progress in heterocyclic synthesis, asymmetric chemistry, and regioselective functionalization. By enabling the efficient synthesis of enantiopure, biologically active molecules, it has become a critical tool in advancing pharmaceutical and chemical research.